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Sample records for sar structure-activity relationship

  1. Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

    Science.gov (United States)

    Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

    2006-11-01

    In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.

  2. Benzoxazolone carboxamides as potent acid ceramidase inhibitors: Synthesis and structure-activity relationship (SAR) studies

    DEFF Research Database (Denmark)

    Bach, Anders

    2015-01-01

    be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We...... examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic...

  3. A Structure-Activity Relationship (SAR Study of Neolignan Compounds with Anti-schistosomiasis Activity

    Directory of Open Access Journals (Sweden)

    Alves Claúdio N.

    2002-01-01

    Full Text Available A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors to be correlated to their biological activities. Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA, discriminant analysis (DA and the Kth nearest neighbor (KNN method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE, molecular refractivity (MR and charge on the C19 carbon atom (Q19. These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.

  4. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities.

    Science.gov (United States)

    Akhtar, Jawaid; Khan, Ahsan Ahmed; Ali, Zulphikar; Haider, Rafi; Shahar Yar, M

    2017-01-05

    The present review article offers a detailed account of the design strategies employed for the synthesis of nitrogen-containing anticancer agents. The results of different studies describe the N-heterocyclic ring system is a core structure in many synthetic compounds exhibiting a broad range of biological activities. Benzimidazole, benzothiazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, triazoles, quinolines and quinazolines including others drugs containing pyridazine, pyridine and pyrimidines are covered. The following studies of these compounds suggested that these compounds showed their antitumor activities through multiple mechanisms including inhibiting protein kinase (CDK, MK-2, PLK1, kinesin-like protein Eg5 and IKK), topoisomerase I and II, microtubule inhibition, and many others. Our concise representation exploits the design and anticancer potency of these compounds. The direct comparison of anticancer activities with the standard enables a systematic analysis of the structure-activity relationship among the series. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Studies on Synthesis and Structure-Activity Relationship (SAR of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase

    Directory of Open Access Journals (Sweden)

    Yongcheng Lin

    2011-10-01

    Full Text Available Based on the natural isoprenyl phenyl ether from a mangrove-derived fungus, 32 analogues were synthesized and evaluated for inhibitory activity against influenza H1N1 neuraminidase. Compound 15 (3-(allyloxy-4-hydroxybenzaldehyde exhibited the most potent inhibitory activity, with IC50 values of 26.96 μM for A/GuangdongSB/01/2009 (H1N1, 27.73 μM for A/Guangdong/03/2009 (H1N1, and 25.13 μM for A/Guangdong/05/2009 (H1N1, respectively, which is stronger than the benzoic acid derivatives (~mM level. These are a new kind of non-nitrogenous aromatic ether Neuraminidase (NA inhibitors. Their structures are simple and the synthesis routes are not complex. The structure-activity relationship (SAR analysis revealed that the aryl aldehyde and unsubstituted hydroxyl were important to NA inhibitory activities. Molecular docking studies were carried out to explain the SAR of the compounds, and provided valuable information for further structure modification.

  6. A New Structure-Activity Relationship (SAR) Model for Predicting Drug-Induced Liver Injury, Based on Statistical and Expert-Based Structural Alerts

    Science.gov (United States)

    Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Benfenati, Emilio

    2016-01-01

    The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model. To extract structural alerts (SAs) related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC) on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81, 63, and 68%, specificity 89, 33, and 33%, sensitivity 93, 88, and 80% and MCC 0.63, 0.27, and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model's architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform. PMID:27920722

  7. A new structure-activity relationship (SAR model for predicting drug-induced liver injury, based on statistical and expert-basedstructural alerts.

    Directory of Open Access Journals (Sweden)

    Fabiola Pizzo

    2016-11-01

    Full Text Available The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80% and test sets (20%. We also compiled an external validation set (101 compounds for evaluating the performance of the model. To extract structural alerts (SAs related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81%, 63% and 68%, specificity 89%, 33% and 33%, sensitivity 93%, 88% and 80% and MCC 0.63, 0.27 and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model’s architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform.

  8. Structure-activity relationship of crustacean peptide hormones.

    Science.gov (United States)

    Katayama, Hidekazu

    2016-01-01

    In crustaceans, various physiological events, such as molting, vitellogenesis, and sex differentiation, are regulated by peptide hormones. To understanding the functional sites of these hormones, many structure-activity relationship (SAR) studies have been published. In this review, the author focuses the SAR of crustacean hyperglycemic hormone-family peptides and androgenic gland hormone and describes the detailed results of our and other research groups. The future perspectives will be also discussed.

  9. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  10. A Review of Recent Advances towards the Development of (Quantitative) Structure-Activity Relationships for Metallic Nanomaterials.

    NARCIS (Netherlands)

    Chen, Guangchao; Vijver, Martina G; Xiao, Yinlong; Peijnenburg, Willie J G M

    2017-01-01

    Gathering required information in a fast and inexpensive way is essential for assessing the risks of engineered nanomaterials (ENMs). The extension of conventional (quantitative) structure-activity relationships ((Q)SARs) approach to nanotoxicology, i.e., nano-(Q)SARs, is a possible solution. The

  11. Molecular Descriptors Family on Structure Activity Relationships 3. Antituberculotic Activity of some Polyhydroxyxanthones

    Directory of Open Access Journals (Sweden)

    Sorana BOLBOACĂ

    2005-06-01

    Full Text Available The antituberculotic activity of some polyhydroxyxanthones was estimated using the Molecular Descriptors Family on Structure Activity Relationships methodology. From a total number of 298110 real and distinct calculated descriptors, 94843 were significantly different and entered into multiple linear regression analysis. The best performing bi-varied model was obtained by use of all polyhydroxyxanthones. The MDF SAR model was validated splitting the molecules into training and test sets. A correlated correlations analysis was applied in other to compare the MDF SAR models with the previous SAR model. The prediction ability of antituberculotic activity of polyhydroxyxanthones with MDF SAR methodology is sustained by three arguments: leave-one-out procedure, training vs. test procedure, and the correlated correlations analysis. Looking at the bi-varied MDF SAR model, we can conclude that the antituberculotic activity of polyhydroxyxanthones is almost of geometrical nature (99% and is strongly dependent on partial atomic charge and group electronegativity.

  12. 3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships.

    Science.gov (United States)

    Dhar, T G Murali; Shen, Zhongqi; Gu, Henry H; Chen, Ping; Norris, Derek; Watterson, Scott H; Ballentine, Shelley K; Fleener, Catherine A; Rouleau, Katherine A; Barrish, Joel C; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

    2003-10-20

    A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.

  13. Structure-Activity Relationships on the Molecular Descriptors Family Project at the End

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2007-12-01

    Full Text Available Molecular Descriptors Family (MDF on the Structure-Activity Relationships (SAR, a promising approach in investigation and quantification of the link between 2D and 3D structural information and the activity, and its potential in the analysis of the biological active compounds is summarized. The approach, attempts to correlate molecular descriptors family generated and calculated on a set of biological active compounds with their observed activity. The estimation as well as prediction abilities of the approach are presented. The obtained MDF SAR models can be used to predict the biological activity of unknown substrates in a series of compounds.

  14. Study of the structure-activity relationships of parabens: a practical class

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Joao Paulo dos Santos; Savino, Giovanna; Amarante, Andre Cortinas Goncalves, E-mail: joao.fernandes@mackenzie.br [Centro de Ciencias Biologicas e da Saude, Universidade Presbiteriana Mackenzie, Sao Paulo, SP (Brazil); Sousa, Milena Rodrigues de; Silva, Geane Ramos da [Universidade Camilo Castelo Branco, Sao Paulo, SP (Brazil); Cianciulli, Maria Eliza [Universidade do Grande ABC, Santo Andre, SP (Brazil); Correa, Michelle Fidelis; Ferrarini, Marcio [Centro Universitario Sao Camilo, Sao Paulo, SP (Brazil)

    2013-09-01

    Parabens are p-hydroxybenzoic acid esters widely used as preservatives. With the aim of teaching the structure-activity relationships (SAR) knowledge in a practical form, this paper proposed a practical class to view the SAR of parabens as antimicrobial agents. Methyl, ethyl, n-propyl, isopropyl and isopentyl paraben compounds were synthesized and their respective antimicrobial activities were assessed through determination of minimum inhibitory concentrations (MIC) against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 stains. With the MIC values, it was possible to verify their correlation with calculated lipophilicity (ClogP). This method can be applied in practical Medicinal Chemistry classes. (author)

  15. Study of the structure-activity relationships of parabens: a practical class

    International Nuclear Information System (INIS)

    Fernandes, João Paulo dos Santos; Savino, Giovanna; Amarante, André Cortinas Gonçalves; Sousa, Milena Rodrigues de; Silva, Geane Ramos da; Cianciulli, Maria Eliza; Corrêa, Michelle Fidelis; Ferrarini, Márcio

    2013-01-01

    Parabens are p-hydroxybenzoic acid esters widely used as preservatives. With the aim of teaching the structure-activity relationships (SAR) knowledge in a practical form, this paper proposed a practical class to view the SAR of parabens as antimicrobial agents. Methyl, ethyl, n-propyl, isopropyl and isopentyl paraben compounds were synthesized and their respective antimicrobial activities were assessed through determination of minimum inhibitory concentrations (MIC) against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 stains. With the MIC values, it was possible to verify their correlation with calculated lipophilicity (ClogP). This method can be applied in practical Medicinal Chemistry classes. (author)

  16. Chemistry and Structure-Activity Relationships of Psychedelics.

    Science.gov (United States)

    Nichols, David E

    2018-01-01

    This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT 2A receptor plays a key role in regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT 2A receptor is the principal mechanism of action for psychedelics, compounds with 5-HT 2A agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to activation of 5-HT 2A receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known.

  17. Structure-activity relationships of bumetanide derivatives

    DEFF Research Database (Denmark)

    Pedersen, Kasper Lykke; Töllner, Kathrin; Römermann, Kerstin

    2015-01-01

    of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. EXPERIMENTAL APPROACH: In this study......, the effect of a series of diuretically active bumetanide derivatives was investigated on human NKCC2 variant A (hNKCC2A) expressed in Xenopus laevis oocytes. KEY RESULTS: Bumetanide blocked hNKCC2A transport with an IC50 of 4 μM. There was good correlation between the diuretic potency of bumetanide and its...... of the structural requirements that determine relative potency of loop diuretics on human NKCC2 splice variants, and may lead to the discovery of novel high-ceiling diuretics....

  18. Quantitative Structure-Activity Relationship Analysis of the ...

    African Journals Online (AJOL)

    Erah

    Quantitative Structure-Activity Relationship Analysis of the Anticonvulsant ... Two types of molecular descriptors, including the 2D autocorrelation ..... It is based on the simulation of natural .... clustering anticonvulsant, antidepressant, and.

  19. The Ghosts of Acetylcholine : structure-activity relationships of ...

    African Journals Online (AJOL)

    The Ghosts of Acetylcholine : structure-activity relationships of muscle relaxants : registrar communication. ... AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...

  20. Structure-activity relationships of diverse xanthones against multidrug resistant human tumor cells.

    Science.gov (United States)

    Wang, Qiwen; Ma, Chenyao; Ma, Yun; Li, Xiang; Chen, Yong; Chen, Jianwei

    2017-02-01

    Thirteen xanthones were isolated naturally from the stem of Securidaca inappendiculata Hassk, and structure-activity relationships (SARs) of these compounds were comparatively predicted for their cytotoxic activity against three human multidrug resistant (MDR) cell lines MCF-7/ADR, SMMC-7721/Taxol, and A549/Taxol cells. The results showed that the selected xanthones exhibited different potent cytotoxic activity against the growth of different human tumor cell lines, and most of the xanthones exhibited selective cytotoxicity against SMMC-7721/Taxol cells. Furthermore, some tested xanthones showed stronger cytotoxicity than Cisplatin, which has been used in clinical application extensively. The SARs analysis revealed that the cytotoxic activities of diverse xanthones were affected mostly by the number and position of methoxyl and hydroxyl groups. Xanthones with more free hydroxyl and methoxyl groups increased the cytotoxic activity significantly, especially for those with the presence of C-3 hydroxyl and C-4 methoxyl groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Structure-activity relationship of surfactant for preparing DMFC anodic catalyst

    International Nuclear Information System (INIS)

    Su Yi; Xue Xinzhong; Xu Weilin; Liu Changpeng; Xing Wei; Zhou Xiaochun; Tian Tian; Lu Tianhong

    2006-01-01

    Three kinds of surfactants as stabilizer were applied to the preparation of electrocatalysts for direct methanol fuel cell (DMFC). The catalysts have been characterized by examining their catalytic activities, morphologies and particle sizes by means of cyclic voltammetry, chronoamperometry, X-ray diffraction and transmission electron microscopy (TEM). It is found that the surfactants with different structures have a significantly influence on the catalyst shape and activity. The catalysts prepared with non-ionic surfactants as the stabilizer show higher activity for direct oxidation of methanol. The structure-activity relationship (SAR) analysis has been explored and the effect of hydrophile-lipophile balance (HLB value) has also been discussed

  2. Investigating the Structure-Activity Relationship of the Insecticidal Natural Product Rocaglamide.

    Science.gov (United States)

    Hall, Roger G; Bruce, Ian; Cooke, Nigel G; Diorazio, Louis J; Cederbaum, Fredrik; Dobler, Markus R; Irving, Ed

    2017-12-01

    The natural product Rocaglamide (1), isolated from the tree Aglaia elliptifolia, is a compelling but also challenging lead structure for crop protection. In laboratory assays, the natural product shows highly interesting insecticidal activity against chewing pests and beetles, but also phytotoxicity on some crop plants. Multi-step syntheses with control of stereochemistry were required to probe the structure-activity relationship (SAR), and seek simplified analogues. After a significant research effort, just two areas of the molecule were identified which allow modification whilst maintaining activity, as will be highlighted in this paper.

  3. A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs.

    Science.gov (United States)

    Cunningham, Albert R; Carrasquer, C Alex; Mattison, Donald R

    2009-01-01

    The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  4. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Cunningham AlbertR

    2009-11-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  5. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Albert R. Cunningham

    2009-01-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  6. Structure-activity relationship studies of citalopram derivatives

    DEFF Research Database (Denmark)

    Larsen, M Andreas B; Plenge, Per; Andersen, Jacob

    2016-01-01

    towards the S2 site. EXPERIMENTAL APPROACH: We performed a systematic structure-activity relationship study based on the scaffold of citalopram and the structurally closely related congener, talopram, that shows low-affinity S1 binding in SERT. The role of the four chemical substituents, which distinguish...... citalopram from talopram in conferring selectivity towards the S1 and S2 site, respectively, was assessed by determining the binding of 14 citalopram/talopram analogous to the S1 and S2 binding sites in SERT using membranes of COS7 cells transiently expressing SERT. KEY RESULTS: The structure-activity...

  7. Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

    Directory of Open Access Journals (Sweden)

    Emmy Tuenter

    2017-02-01

    Full Text Available Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship models were developed, using PLS (partial least squares regression and MLR (multiple linear regression. On the one hand, these models allow for the indication of the most important descriptors (molecular properties responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study.

  8. Structure and Structure-activity Relationship of Functional Organic Molecules

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Research theme The group is made up of junior scientists from the State Key Laboratory of Elemento-organic Chemistry, Nankai University.The scientists focus their studis on the structure and structure-activity relationship of functional organic molecules not only because it has been the basis of their research, but also because the functional study of organic compounds is now a major scientific issue for organic chemists around the world.

  9. Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression.

    Science.gov (United States)

    Toyota, Yosuke; Nomura, Sayaka; Makishima, Makoto; Hashimoto, Yuichi; Ishikawa, Minoru

    2017-06-15

    Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC 50 : 14μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

    Science.gov (United States)

    Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

    2006-06-01

    The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

  11. Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

    Science.gov (United States)

    Carbone, V; Kim, H; Huang, J X; Baker, M A; Ong, C; Cooper, M A; Li, J; Rockman, S; Velkov, T

    2013-01-01

    Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.

  12. Multistep continuous-flow synthesis in medicinal chemistry: discovery and preliminary structure-activity relationships of CCR8 ligands.

    Science.gov (United States)

    Petersen, Trine P; Mirsharghi, Sahar; Rummel, Pia C; Thiele, Stefanie; Rosenkilde, Mette M; Ritzén, Andreas; Ulven, Trond

    2013-07-08

    A three-step continuous-flow synthesis system and its application to the assembly of a new series of chemokine receptor ligands directly from commercial building blocks is reported. No scavenger columns or solvent switches are necessary to recover the desired test compounds, which were obtained in overall yields of 49-94%. The system is modular and flexible, and the individual steps of the sequence can be interchanged with similar outcome, extending the scope of the chemistry. Biological evaluation confirmed activity on the chemokine CCR8 receptor and provided initial structure-activity-relationship (SAR) information for this new ligand series, with the most potent member displaying full agonist activity with single-digit nanomolar potency. To the best of our knowledge, this represents the first published example of efficient use of multistep flow synthesis combined with biological testing and SAR studies in medicinal chemistry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567.

    Science.gov (United States)

    Kuduk, Scott D; Di Marco, Christina N; Bodmer-Narkevitch, Vera; Cook, Sean P; Cato, Matthew J; Jovanovska, Aneta; Urban, Mark O; Leitl, Michael; Sain, Nova; Liang, Annie; Spencer, Robert H; Kane, Stefanie A; Hartman, George D; Bilodeau, Mark T

    2010-01-20

    The synthesis, structure-activity relationship (SAR), and pharmacological evaluation of analogs of the acid-sensing ion channel (ASIC) inhibitor A-317567 are reported. It was found that the compound with an acetylenic linkage was the most potent ASIC-3 channel blocker. This compound reversed mechanical hypersensitivity in the rat iodoacetate model of osteoarthritis pain, although sedation was noted. Sedation was also observed in ASIC-3 knockout mice, questioning whether sedation and antinociception are mediated via a non-ASIC-3 specific mechanism.

  14. Designing a Quantitative Structure-Activity Relationship for the ...

    Science.gov (United States)

    Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemicals including nearly 8000 chemicals tested for in vitro bioactivity in the Tox21 program. To address this gap, a quantitative structure-activity relationship (QSAR) for intrinsic metabolic clearance rate was developed to offer reliable in silico predictions for a diverse array of chemicals. Models were constructed with curated in vitro assay data for both pharmaceutical-like chemicals (ChEMBL database) and environmentally relevant chemicals (ToxCast screening) from human liver microsomes (2176 from ChEMBL) and human hepatocytes (757 from ChEMBL and 332 from ToxCast). Due to variability in the experimental data, a binned approach was utilized to classify metabolic rates. Machine learning algorithms, such as random forest and k-nearest neighbor, were coupled with open source molecular descriptors and fingerprints to provide reasonable estimates of intrinsic metabolic clearance rates. Applicability domains defined the optimal chemical space for predictions, which covered environmental chemicals well. A reduced set of informative descriptors (including relative charge and lipophilicity) and a mixed training set of pharmaceuticals and environmentally relevant chemicals provided the best intr

  15. Structure activity relationships to assess new chemicals under TSCA

    Energy Technology Data Exchange (ETDEWEB)

    Auletta, A.E. [Environmental Protection Agency, Washington, DC (United States)

    1990-12-31

    Under Section 5 of the Toxic Substances Control Act (TSCA), manufacturers must notify the US Environmental Protection Agency (EPA) 90 days before manufacturing, processing, or importing a new chemical substance. This is referred to as a premanufacture notice (PMN). The PMN must contain certain information including chemical identity, production volume, proposed uses, estimates of exposure and release, and any health or environmental test data that are available to the submitter. Because there is no explicit statutory authority that requires testing of new chemicals prior to their entry into the market, most PMNs are submitted with little or no data. As a result, EPA has developed special techniques for hazard assessment of PMN chemicals. These include (1) evaluation of available data on the chemical itself, (2) evaluation of data on analogues of the PMN, or evaluation of data on metabolites or analogues of metabolites of the PMN, (3) use of quantitative structure activity relationships (QSARs), and (4) knowledge and judgement of scientific assessors in the interpretation and integration of the information developed in the course of the assessment. This approach to evaluating potential hazards of new chemicals is used to identify those that are most in need of addition review of further testing. It should not be viewed as a replacement for testing. 4 tabs.

  16. Structure-activity relationships of strychnine analogues at glycine receptors

    DEFF Research Database (Denmark)

    Mohsen, A.M.Y.; Heller, Eberhard; Holzgrabe, Ulrike

    2014-01-01

    Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best...... pharmacological profile exhibiting an IC50 value of 1.6 μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21)[DOUBLE BOND]C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine...

  17. Structure-activity relationship of CART peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Elbert, Tomáš; Šanda, Miloslav; Slaninová, Jiřina; Železná, Blanka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 565 ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : cocaine and amphetamine regulated transcript peptide * structure * activity Subject RIV: CE - Biochemistry

  18. Structure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439).

    Science.gov (United States)

    Dong, Yuxiang; Wang, Xiaofang; Kamaraj, Sriraghavan; Bulbule, Vivek J; Chiu, Francis C K; Chollet, Jacques; Dhanasekaran, Manickam; Hein, Christopher D; Papastogiannidis, Petros; Morizzi, Julia; Shackleford, David M; Barker, Helena; Ryan, Eileen; Scheurer, Christian; Tang, Yuanqing; Zhao, Qingjie; Zhou, Lin; White, Karen L; Urwyler, Heinrich; Charman, William N; Matile, Hugues; Wittlin, Sergio; Charman, Susan A; Vennerstrom, Jonathan L

    2017-04-13

    Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK a and lower log D 7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D 7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

  19. Synthesis and anticancer structure activity relationship investigation of cationic anthraquinone analogs.

    Science.gov (United States)

    Shrestha, Jaya P; Fosso, Marina Y; Bearss, Jeremiah; Chang, Cheng-Wei Tom

    2014-04-22

    We have synthesized a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which can be viewed as analogs of cationic anthraquinones. Unlike the similar analogs that we have reported previously, these compounds show relatively weak antibacterial activities but exert strong anticancer activities (low μM to nM GI50), in particular, against melanoma, colon cancer, non-small cell lung cancer and central nervous system (CNS) cancer. These compounds are structurally different from their predecessors by having the aromatic group, instead of alkyl chains, directly attached to the cationic anthraquinone scaffold. Further investigation in the structure-activity relationship (SAR) reveals the significant role of electron donating substituents on the aromatic ring in enhancing the anticancer activities via resonance effect. Steric hindrance of these groups is disadvantageous but is less influential than the resonance effect. The difference in the attached groups at N-1 position of the cationic anthraquinone analog is the main structural factor for the switching of biological activity from antibacterial to anticancer. The discovery of these compounds may lead to the development of novel cancer chemotherapeutics. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Biosynthetically Guided Structure-Activity Relationship Studies of Merochlorin A, an Antibiotic Marine Natural Product.

    Science.gov (United States)

    López-Pérez, Borja; Pepper, Henry P; Ma, Rong; Fawcett, Benjamin J; Pehere, Ashok D; Wei, Qi; Ji, Zengchun; Polyak, Steven W; Dai, Huanqin; Song, Fuhang; Abell, Andrew D; Zhang, Lixin; George, Jonathan H

    2017-12-07

    The onset of new multidrug-resistant strains of bacteria demands continuous development of antibacterial agents with new chemical scaffolds and mechanisms of action. We present the first structure-activity relationship (SAR) study of 16 derivatives of a structurally novel antibiotic merochlorin A that were designed using a biosynthetic blueprint. Our lead compounds are active against several Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are relatively nontoxic to human cell lines. Furthermore, derivative 12 c {(±)-(3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione} was found to inhibit the growth of Bacillus Calmette-Guérin (BCG)-infected cells at concentrations similar to rifampicin. These results outperform the natural product, underscoring the potential of merochlorin analogues as a new class of antibiotics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

    Science.gov (United States)

    Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

    2002-01-07

    A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

  2. Seamless integration of dose-response screening and flow chemistry: efficient generation of structure-activity relationship data of β-secretase (BACE1) inhibitors.

    Science.gov (United States)

    Werner, Michael; Kuratli, Christoph; Martin, Rainer E; Hochstrasser, Remo; Wechsler, David; Enderle, Thilo; Alanine, Alexander I; Vogel, Horst

    2014-02-03

    Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure-activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a flow-based biochemical assay and its seamless integration into a fully automated system comprising flow chemical synthesis, purification and in-line quantification of compound concentration. This novel synthesis-screening platform enables to obtain SAR data on b-secretase (BACE1) inhibitors at an unprecedented cycle time of only 1 h instead of several days. Full integration and automation of industrial processes have always led to productivity gains and cost reductions, and this work demonstrates how applying these concepts to SAR generation may lead to a more efficient drug discovery process. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Modeling Chemical Interaction Profiles: I. Spectral Data-Activity Relationship and Structure-Activity Relationship Models for Inhibitors and Non-inhibitors of Cytochrome P450 CYP3A4 and CYP2D6 Isozymes

    OpenAIRE

    McPhail, Brooks; Tie, Yunfeng; Hong, Huixiao; Pearce, Bruce A.; Schnackenberg, Laura K.; Ge, Weigong; Valerio, Luis G.; Fuscoe, James C.; Tong, Weida; Buzatu, Dan A.; Wilkes, Jon G.; Fowler, Bruce A.; Demchuk, Eugene; Beger, Richard D.

    2012-01-01

    An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals—drugs, pesticides, and environmental pollutants—interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP) enzymes. In the present work, spectral data-activity relationship (SDAR) and structure-activity relationship (SAR) approaches were used to develop machine-learning classifi...

  4. Molecular Descriptors Family on Structure Activity Relationships 1. Review of the Methodology

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2005-01-01

    Full Text Available This review cumulates the knowledge about the use of Molecular Descriptors Family usage on Structure Activity Relationships. The methodology is augmented through the general Structure Activity Relationships methodology. The obtained models in a series of five papers are quantitatively analyzed by comparing with previous reported results by using of the correlated correlations tests. The scores for a series of 13 data sets unpublished yet results are presented. Two unrestricted online access portals to the Molecular Descriptors Family Structure Activity Relationship models results are given.

  5. Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessments.

    Science.gov (United States)

    Comber, Mike H I; Walker, John D; Watts, Chris; Hermens, Joop

    2003-08-01

    The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed.

  6. Synthesis and Structure-Activity Relationships of Novel Amino/Nitro Substituted 3-Arylcoumarins as Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Ysabel Santos

    2013-01-01

    Full Text Available A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive and Escherichia coli (Gram-negative was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin. The preliminary structure-activity relationship (SAR study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported.

  7. Synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors.

    Science.gov (United States)

    Zeng, Debin; Ma, Yuying; Zhang, Rui; Nie, Quandeng; Cui, Zhengjie; Wang, Yaxin; Shang, Luqing; Yin, Zheng

    2016-04-01

    α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26μM, 1.88±0.35μM and 1.52±0.31μM, respectively) and favorable CC50 values (CC50>100μM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Improving the applicability of (Q)SARs for percutaneous penetration in regulatory risk assessment.

    NARCIS (Netherlands)

    Bouwman, T.; Cronin, M.T.; Bessems, J.G.; Sandt, J.J. van de

    2008-01-01

    The new regulatory framework REACH (Registration, Evaluation, and Authorisation of Chemicals) foresees the use of non-testing approaches, such as read-across, chemical categories, structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs). Although information

  9. Structure-activity relationship analysis of cytotoxic cyanoguanidines: selection of CHS 828 as candidate drug

    Directory of Open Access Journals (Sweden)

    Gullbo Joachim

    2009-06-01

    ten cell lines were compared. Substances with similar structures correlated well, whilst substances with large differences in molecular structure demonstrated lower correlation coefficients. Conclusion According to this structure-activity relationship (SAR study, CHS 828 meets the requirements for optimal cytotoxic activity for this class of compounds.

  10. Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

    Science.gov (United States)

    Argade, Ankush; Bhamidipati, Somasekhar; Li, Hui; Carroll, David; Clough, Jeffrey; Keim, Holger; Sylvain, Catherine; Rossi, Alexander B; Coquilla, Christina; Issakani, Sarkiz D; Masuda, Esteban S; Payan, Donald G; Singh, Rajinder

    2015-01-01

    Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

    DEFF Research Database (Denmark)

    Gimenéz-Arnau, Elena; Andersen, K E; Bruze, M

    2000-01-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application...

  12. Quantitative Structure-Activity Relationships and Docking Studies of Calcitonin Gene-Related Peptide Antagonists

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range...... of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression....... The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model...

  13. Structure-activity relationship studies of the aromatic positions in cyclopentapeptide CXCR4 antagonists

    DEFF Research Database (Denmark)

    Mungalpara, Jignesh; Zachariassen, Zack G; Thiele, Stefanie

    2013-01-01

    , and autoimmune diseases. While the structure-activity relationships for Arg(1), Arg(2), and Gly(4) are well established, less is understood about the roles of the aromatic residues 2-Nal(3) and D-Tyr(5). Here we report further structure-activity relationship studies of these two positions, which showed that (i......) the distal aromatic ring of the 2-Nal(3) side chain is required in order to maintain high potency and (ii) replacement of D-Tyr(5) with conformationally constrained analogues results in significantly reduced activity. However, a simplified analogue that contained Gly instead of D-Tyr(5) was only 13-fold less...

  14. A biology-based approach for quantitative structure-activity relationships (QSARs) in ecotoxicity.

    NARCIS (Netherlands)

    Jager, T.; Kooijman, S.A.L.M.

    2009-01-01

    Quantitative structure-activity relationships (QSARs) for ecotoxicity can be used to fill data gaps and limit toxicity testing on animals. QSAR development may additionally reveal mechanistic information based on observed patterns in the data. However, the use of descriptive summary statistics for

  15. Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

    NARCIS (Netherlands)

    Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik

    After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural

  16. Environmental properties of long-chain alcohols. Structure-activity Relationship for Chronic Aquatic Toxicity

    DEFF Research Database (Denmark)

    Schaefers, Christoph; Sanderson, Hans; Boshof, Udo

    2009-01-01

    Daphnia magna reproduction tests were performed with C10, C12, C14 and C15 alcohols to establish a structure-activity relationship of chronic effects of long-chain alcohols. The data generation involved substantial methodological efforts due to the exceptionally rapid biodegradability of the test...

  17. Determination of boiling point of petrochemicals by gas chromatography-mass spectrometry and multivariate regression analysis of structural activity relationship.

    Science.gov (United States)

    Fakayode, Sayo O; Mitchell, Breanna S; Pollard, David A

    2014-08-01

    Accurate understanding of analyte boiling points (BP) is of critical importance in gas chromatographic (GC) separation and crude oil refinery operation in petrochemical industries. This study reported the first combined use of GC separation and partial-least-square (PLS1) multivariate regression analysis of petrochemical structural activity relationship (SAR) for accurate BP determination of two commercially available (D3710 and MA VHP) calibration gas mix samples. The results of the BP determination using PLS1 multivariate regression were further compared with the results of traditional simulated distillation method of BP determination. The developed PLS1 regression was able to correctly predict analytes BP in D3710 and MA VHP calibration gas mix samples, with a root-mean-square-%-relative-error (RMS%RE) of 6.4%, and 10.8% respectively. In contrast, the overall RMS%RE of 32.9% and 40.4%, respectively obtained for BP determination in D3710 and MA VHP using a traditional simulated distillation method were approximately four times larger than the corresponding RMS%RE of BP prediction using MRA, demonstrating the better predictive ability of MRA. The reported method is rapid, robust, and promising, and can be potentially used routinely for fast analysis, pattern recognition, and analyte BP determination in petrochemical industries. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors.

    Science.gov (United States)

    Ma, Fei; Liu, Jian; Zhou, Tingting; Lei, Min; Chen, Jing; Wang, Xiachang; Zhang, Yinan; Shen, Xu; Hu, Lihong

    2018-05-25

    Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC 50  = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF 3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC 50  = 16.8 μM) and 9d (IC 50  = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  19. Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.

    Science.gov (United States)

    Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L

    2016-03-23

    Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Selective kappa-opioid agonists: synthesis and structure-activity relationships of piperidines incorporating on oxo-containing acyl group.

    Science.gov (United States)

    Giardina, G; Clarke, G D; Dondio, G; Petrone, G; Sbacchi, M; Vecchietti, V

    1994-10-14

    This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using kappa-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2- naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 mumol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective kappa-agonists, has a reduced propensity to cause a number of kappa-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 mumol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

  1. Modifiers in rhodium catalysts for carbon monoxide hydrogenation: Structure-activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Bhore, N. A.

    1989-05-01

    This report is aimed at identifying interesting modified rhodium systems and elucidating structure-activity relationships in these systems with the overall goal of understanding the scientific issues in the catalytic conversion of syngas to oxygenates. Specific additives (sodium and molybdenum) are selected based on the scoping experiments. The effect of the additives on supported rhodium catalysts is then investigated. Throughout the investigation, experiments and analysis were performed on real systems instead of ideal systems. 374 refs., 82 figs., 57 tabs.

  2. Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

    Czech Academy of Sciences Publication Activity Database

    Eyer, L.; Šmídková, Markéta; Nencka, Radim; Neča, J.; Kastl, T.; Palus, Martin; De Clercq, E.; Růžek, Daniel

    2016-01-01

    Roč. 133, Sep (2016), s. 119-129 ISSN 0166-3542 R&D Projects: GA MZd(CZ) NV16-34238A; GA ČR(CZ) GA16-20054S Institutional support: RVO:61388963 ; RVO:60077344 Keywords : structure-activity relationship * tick-borne encephalitis * nucleoside inhibitor * antiviral activity * cytotoxicity Subject RIV: CC - Organic Chemistry; EE - Microbiology, Virology (BC-A) Impact factor: 4.271, year: 2016

  3. Modeling Chemical Interaction Profiles: I. Spectral Data-Activity Relationship and Structure-Activity Relationship Models for Inhibitors and Non-inhibitors of Cytochrome P450 CYP3A4 and CYP2D6 Isozymes

    Directory of Open Access Journals (Sweden)

    Richard D. Beger

    2012-03-01

    Full Text Available An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals—drugs, pesticides, and environmental pollutants—interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP enzymes. In the present work, spectral data-activity relationship (SDAR and structure-activity relationship (SAR approaches were used to develop machine-learning classifiers of inhibitors and non-inhibitors of the CYP3A4 and CYP2D6 isozymes. The models were built upon 602 reference pharmaceutical compounds whose interactions have been deduced from clinical data, and 100 additional chemicals that were used to evaluate model performance in an external validation (EV test. SDAR is an innovative modeling approach that relies on discriminant analysis applied to binned nuclear magnetic resonance (NMR spectral descriptors. In the present work, both 1D 13C and 1D 15N-NMR spectra were used together in a novel implementation of the SDAR technique. It was found that increasing the binning size of 1D 13C-NMR and 15N-NMR spectra caused an increase in the tenfold cross-validation (CV performance in terms of both the rate of correct classification and sensitivity. The results of SDAR modeling were verified using SAR. For SAR modeling, a decision forest approach involving from 6 to 17 Mold2 descriptors in a tree was used. Average rates of correct classification of SDAR and SAR models in a hundred CV tests were 60% and 61% for CYP3A4, and 62% and 70% for CYP2D6, respectively. The rates of correct classification of SDAR and SAR models in the EV test were 73% and 86% for CYP3A4, and 76% and 90% for CYP2D6, respectively. Thus, both SDAR and SAR methods demonstrated a comparable performance in modeling a large set of structurally diverse data. Based on unique NMR structural descriptors, the new SDAR modeling method complements the existing SAR

  4. Calculation of Quantitative Structure-Activity Relationship Descriptors of Artemisinin Derivatives

    Directory of Open Access Journals (Sweden)

    Jambalsuren Bayarmaa

    2008-06-01

    Full Text Available Quantitative structure-activity relationships are based on the construction of predictive models using a set of known molecules and associated activity value. This accurate methodology, developed with adequate mathematical and computational tools, leads to a faster, cheaper and more comprehensive design of new products, reducing the experimental synthesis and testing on animals. Preparation of the QSAR models of artemisinin derivatives was carried out by the genetic function algorithm (GFA method for 91 molecules. The results show some relationships to the observed antimalarial activities of the artemisinin derivatives. The most statistically signi fi cant regression equation obtained from the fi nal GFA relates to two molecular descriptors.

  5. Structure determination of glycogen synthase kinase-3 from Leishmania major and comparative inhibitor structure-activity relationships with Trypanosoma brucei GSK-3

    Energy Technology Data Exchange (ETDEWEB)

    Ojo, Kayode K; Arakaki, Tracy L; Napuli, Alberto J; Inampudi, Krishna K; Keyloun, Katelyn R; Zhang, Li; Hol, Wim G.J.; Verlind, Christophe L.M.J.; Merritt, Ethan A; Van Voorhis, Wesley C [UWASH

    2012-04-24

    Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation in pharmaceutical companies and constitutes an attractive piggyback target for eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about 150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has previously been validated genetically as a drug target in Trypanosoma brucei by RNAi induced growth retardation; and chemically by correlation between enzyme and in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3 short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270, identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of LmajGSK-3 short at 2 Å resolution. The inhibitor structure-activity relationships (SARs) of L. major and L. infantum are virtually identical, suggesting that inhibitors could be useful for both cutaneous and visceral leishmaniasis. Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short, which can be explained mostly by two variant residues in the ATP-binding pocket. Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR more similar to that of TbruGSK-3 short. The differences between human GSK-3β (HsGSK-3β) and LmajGSK-3 short SAR suggest that compounds which selectively inhibit LmajGSK-3 short may be found.

  6. Interaction of cholesterol-conjugated ionizable amino lipids with biomembranes: lipid polymorphism, structure-activity relationship, and implications for siRNA delivery.

    Science.gov (United States)

    Zhang, Jingtao; Fan, Haihong; Levorse, Dorothy A; Crocker, Louis S

    2011-08-02

    Delivery of siRNA is a major obstacle to the advancement of RNAi as a novel therapeutic modality. Lipid nanoparticles (LNP) consisting of ionizable amino lipids are being developed as an important delivery platform for siRNAs, and significant efforts are being made to understand the structure-activity relationship (SAR) of the lipids. This article uses a combination of small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) to evaluate the interaction between cholesterol-conjugated ionizable amino lipids and biomembranes, focusing on an important area of lipid SAR--the ability of lipids to destabilize membrane bilayer structures and facilitate endosomal escape. In this study, cholesterol-conjugated amino lipids were found to be effective in increasing the order of biomembranes and also highly effective in inducing phase changes in biological membranes in vitro (i.e., the lamellar to inverted hexagonal phase transition). The phase transition temperatures, determined using SAXS and DSC, serve as an indicator for ranking the potency of lipids to destabilize endosomal membranes. It was found that the bilayer disruption ability of amino lipids depends strongly on the amino lipid concentration in membranes. Amino lipids with systematic variations in headgroups, the extent of ionization, tail length, the degree of unsaturation, and tail asymmetry were evaluated for their bilayer disruption ability to establish SAR. Overall, it was found that the impact of these lipid structure changes on their bilayer disruption ability agrees well with the results from a conceptual molecular "shape" analysis. Implications of the findings from this study for siRNA delivery are discussed. The methods reported here can be used to support the SAR screening of cationic lipids for siRNA delivery, and the information revealed through the study of the interaction between cationic lipids and biomembranes will contribute significantly to the design of more efficient si

  7. Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

    Science.gov (United States)

    Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

    2014-12-15

    Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Quantitative Structure activity relationship and risk analysis of some pesticides in the cattle milk

    OpenAIRE

    Faqir Muhammad*, Ijaz Javed, Masood Akhtar1, Zia-ur-Rahman, Mian Muhammad Awais1, Muhammad Kashif Saleemi2 and Muhammad Irfan Anwar3

    2012-01-01

    Milk of cattle was collected from various localities of Faisalabad, Pakistan. Pesticides concentration was determined by HPLC using solid phase microextraction. The residue analysis revealed that about 40% milk samples were contaminated with pesticides. The mean±SE levels (ppm) of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.38±0.02, 0.26±0.02, 0.072±0.01 and 0.085±0.02, respectively. Quantitative structure activity relationship (QSAR) models were used to predict the residues...

  9. Structure-activity relationship study of oxindole-based inhibitors of cyclin-dependent kinases based on least-squares support vector machines

    International Nuclear Information System (INIS)

    Li Jiazhong; Liu Huanxiang; Yao Xiaojun; Liu Mancang; Hu Zhide; Fan Botao

    2007-01-01

    The least-squares support vector machines (LS-SVMs), as an effective modified algorithm of support vector machine, was used to build structure-activity relationship (SAR) models to classify the oxindole-based inhibitors of cyclin-dependent kinases (CDKs) based on their activity. Each compound was depicted by the structural descriptors that encode constitutional, topological, geometrical, electrostatic and quantum-chemical features. The forward-step-wise linear discriminate analysis method was used to search the descriptor space and select the structural descriptors responsible for activity. The linear discriminant analysis (LDA) and nonlinear LS-SVMs method were employed to build classification models, and the best results were obtained by the LS-SVMs method with prediction accuracy of 100% on the test set and 90.91% for CDK1 and CDK2, respectively, as well as that of LDA models 95.45% and 86.36%. This paper provides an effective method to screen CDKs inhibitors

  10. Antimitotic antitumor agents: synthesis, structure-activity relationships, and biological characterization of N-aryl-N'-(2-chloroethyl)ureas as new selective alkylating agents.

    Science.gov (United States)

    Mounetou, E; Legault, J; Lacroix, J; C-Gaudreault, R

    2001-03-01

    A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl ring or a fluorenyl/indanyl group, (ii) an exocyclic urea function, and (iii) a N'-2-chloroethyl moiety were required to ensure significant cytotoxicity. Biological experiments, such as immunofluorescence microscopy, confirmed that these promising compounds alter the cytoskeleton by inducing microtubule depolymerization via selective alkylation of beta-tubulin. Subsequent evaluations demonstrated that potent CEUs were weak alkylators, were non-DNA-damaging agents, and did not interact with the thiol function of either glutathione or glutathione reductase. Therefore, CEUs are part of a new class of antimitotic agents. Finally, among the series of CEUs evaluated, compounds 12, 15, 16, and 27 were selected for further in vivo trials.

  11. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

    DEFF Research Database (Denmark)

    Arnau, E G; Andersen, Klaus Ejner; Bruze, M

    2000-01-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application......" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance...

  12. Structure-activity relationships between sterols and their thermal stability in oil matrix.

    Science.gov (United States)

    Hu, Yinzhou; Xu, Junli; Huang, Weisu; Zhao, Yajing; Li, Maiquan; Wang, Mengmeng; Zheng, Lufei; Lu, Baiyi

    2018-08-30

    Structure-activity relationships between 20 sterols and their thermal stabilities were studied in a model oil system. All sterol degradations were found to be consistent with a first-order kinetic model with determination of coefficient (R 2 ) higher than 0.9444. The number of double bonds in the sterol structure was negatively correlated with the thermal stability of sterol, whereas the length of the branch chain was positively correlated with the thermal stability of sterol. A quantitative structure-activity relationship (QSAR) model to predict thermal stability of sterol was developed by using partial least squares regression (PLSR) combined with genetic algorithm (GA). A regression model was built with R 2 of 0.806. Almost all sterol degradation constants can be predicted accurately with R 2 of cross-validation equals to 0.680. Four important variables were selected in optimal QSAR model and the selected variables were observed to be related with information indices, RDF descriptors, and 3D-MoRSE descriptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Biosynthesis and structure-activity relationships of the lipid a family of glycolipids.

    Science.gov (United States)

    Xiao, Xirui; Sankaranarayanan, Karthik; Khosla, Chaitan

    2017-10-01

    Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the amphipathic glycolipid moiety of LPS. It stimulates the immune system by tightly binding to Toll-like receptor 4. More recently, Lipid A has also been shown to activate intracellular caspase-4 and caspase-5. An impressive diversity is observed in Lipid A structures from different Gram-negative bacteria, and it is well established that subtle changes in chemical structure can result in dramatically different immune activities. For example, Lipid A from Escherichia coli is highly toxic to humans, whereas a biosynthetic precursor called Lipid IV A blocks this toxic activity, and monophosphoryl Lipid A from Salmonella minnesota is a vaccine adjuvant. Thus, an understanding of structure-activity relationships in this glycolipid family could be used to design useful immunomodulatory agents. Here we review the biosynthesis, modification, and structure-activity relationships of Lipid A. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The effect of leverage and/or influential on structure-activity relationships.

    Science.gov (United States)

    Bolboacă, Sorana D; Jäntschi, Lorentz

    2013-05-01

    In the spirit of reporting valid and reliable Quantitative Structure-Activity Relationship (QSAR) models, the aim of our research was to assess how the leverage (analysis with Hat matrix, h(i)) and the influential (analysis with Cook's distance, D(i)) of QSAR models may reflect the models reliability and their characteristics. The datasets included in this research were collected from previously published papers. Seven datasets which accomplished the imposed inclusion criteria were analyzed. Three models were obtained for each dataset (full-model, h(i)-model and D(i)-model) and several statistical validation criteria were applied to the models. In 5 out of 7 sets the correlation coefficient increased when compounds with either h(i) or D(i) higher than the threshold were removed. Withdrawn compounds varied from 2 to 4 for h(i)-models and from 1 to 13 for D(i)-models. Validation statistics showed that D(i)-models possess systematically better agreement than both full-models and h(i)-models. Removal of influential compounds from training set significantly improves the model and is recommended to be conducted in the process of quantitative structure-activity relationships developing. Cook's distance approach should be combined with hat matrix analysis in order to identify the compounds candidates for removal.

  15. Quantitative structure-activity relationship of some 1-benzylbenzimidazole derivatives as antifungal agents

    Directory of Open Access Journals (Sweden)

    Podunavac-Kuzmanović Sanja O.

    2007-01-01

    Full Text Available In the present study, the antifungal activity of some 1-benzylbenzimidazole derivatives against yeast Saccharomyces cerevisiae was investigated. The tested benzimidazoles displayed in vitro antifungal activity and minimum inhibitory concentration (MIC was determined for all the compounds. Quantitative structure-activity relationship (QSAR has been used to study the relationships between the antifungal activity and lipophilicity parameter, logP, calculated by using CS Chem-Office Software version 7.0. The results are discussed on the basis of statistical data. The best QSAR model for prediction of antifungal activity of the investigated series of benzimidazoles was developed. High agreement between experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antifungal activity of this class of compounds, which simplify design of new biologically active molecules.

  16. Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants

    NARCIS (Netherlands)

    Harju, M.; Hamers, T.; Kamstra, J.H.; Sonneveld, E.; Boon, J.P.

    2007-01-01

    In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs),

  17. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

    Science.gov (United States)

    Arnau, E G; Andersen, K E; Bruze, M; Frosch, P J; Johansen, J D; Menné, T; Rastogi, S C; White, I R; Lepoittevin, J P

    2000-12-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

  18. Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling.

    Science.gov (United States)

    Mori, Yoshikazu; Hirokawa, Takatsugu; Aoki, Katsuyuki; Satomi, Hisanori; Takeda, Shuichi; Aburada, Masaki; Miyamoto, Ken-ichi

    2008-05-01

    We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFbeta R-ligand interactions, is urgently needed. Here we present models of the PDGFbeta R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by alpha-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFbeta R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors.

  19. Antitumor potential of crown ethers: structure-activity relationships, cell cycle disturbances, and cell death studies of a series of ionophores.

    Science.gov (United States)

    Marjanović, Marko; Kralj, Marijeta; Supek, Fran; Frkanec, Leo; Piantanida, Ivo; Smuc, Tomislav; Tusek-Bozić, Ljerka

    2007-03-08

    The present paper demonstrates the antiproliferative ability and structure-activity relationships (SAR) of 14 crown and aza-crown ether analogues on five tumor-cell types. The most active compounds were di-tert-butyldicyclohexano-18-crown-6 (3), which exhibited cytotoxicity in the submicromolar range, and di-tert-butyldibenzo-18-crown-6 (5) (IC50 values of approximately 2 microM). Also, 3 and 5 induced marked influence on the cell cycle phase distribution--strong G1 arrest, followed by the induction of apoptosis. A computational SAR modeling effort offers insight into possible mechanisms of crown ether biological activity, presumably involving penetration into cell membranes, and points out structural features of molecules important for this activity. The results reveal that crown ethers possess marked tumor-cell growth inhibitory activity, the extent of which depends on the characteristics of the hydrophilic macrocylic cavity and the surrounding hydrophobic ring. Our work supports the hypothesis that crown ether compounds inhibit tumor-cell growth by disrupting potassium ion homeostasis, which in turn leads to cell cycle perturbations and apoptosis.

  20. Lipid A structural modifications in extreme conditions and identification of unique modifying enzymes to define the Toll-like receptor 4 structure-activity relationship.

    Science.gov (United States)

    Scott, Alison J; Oyler, Benjamin L; Goodlett, David R; Ernst, Robert K

    2017-11-01

    Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant. A limited 'toolbox' of lipid A-modifying enzymes has been defined and is largely composed of enzymes from mesophile human and zoonotic pathogens. Expansion of this 'toolbox' will result from extending the search into lipid A biosynthesis and modification by bacteria living at the extremes. Here, we review the fundamentals of lipid A structure, advances in lipid A uses in TLR4 modulation, and the search for novel lipid A-modifying systems in extremophile bacteria. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Quantitative Structure Activity Relationship of Cinnamaldehyde Compounds against Wood-Decaying Fungi

    Directory of Open Access Journals (Sweden)

    Dongmei Yang

    2016-11-01

    Full Text Available Cinnamaldehyde, of the genius Cinnamomum, is a major constituent of the bark of the cinnamon tree and possesses broad-spectrum antimicrobial activity. In this study, we used best multiple linear regression (BMLR to develop quantitative structure activity relationship (QSAR models for cinnamaldehyde derivatives against wood-decaying fungi Trametes versicolor and Gloeophyllun trabeum. Based on the two optimal QSAR models, we then designed and synthesized two novel cinnamaldehyde compounds. The QSAR models exhibited good correlation coefficients: R2Tv = 0.910 for Trametes versicolor and R2Gt = 0.926 for Gloeophyllun trabeum. Small errors between the experimental and calculated values of two designed compounds indicated that these two QSAR models have strong predictability and stability.

  2. Structure-activity relationships of heterogeneous catalysts from time-resolved X-ray absorption spectroscopy

    International Nuclear Information System (INIS)

    Ressler, T.; Jentoft, R.E.; Wienold, J.; Girgsdies, F.; Neisius, T.; Timpe, O.

    2003-01-01

    Knowing the composition and the evolution of the bulk structure of a heterogeneous catalyst under working conditions (in situ) is a pre-requisite for understanding structure-activity relationships. X-ray absorption spectroscopy can be employed to study a catalytically active material in situ. In addition to steady-state investigations, the technique permits experiments with a time-resolution in the sub-second range to elucidate the solid-state kinetics of the reactions involved. Combined with mass spectrometry, the evolution of the short-range order structure of a heterogeneous catalyst, the average valence of the constituent metals, and the phase composition can be obtained. Here we present results obtained from time-resolved studies on the reduction of MoO 3 in propene and in propene and oxygen

  3. Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects

    International Nuclear Information System (INIS)

    Iorio, L.C.; Billiard, W.; Gold, E.H.

    1986-01-01

    This chapter describes the displacement of 3 H-23390 and 3 H-spiperone binding by dopamine agonists and antagonists. The authors undertook an evaluation of the ability of selected analogs of SCH 23390 to displace 3 H-SCH 23390 and 3 H-spiperone. Structure-activity relationships of SCH 23390 analogs: 7-position substituents, is shown. It is shown that, in general, benzazepines with a variety of substituents in the 7-position retain their selectivity for D 1 sites. Substituents at the 8-position and at the N-position are also discussed. The authors determine a correlation between displacement of 3 H-SCH 23390 and blockade of dopamine-sensitive adenylate cyclase (DSAC). These effects and inhibition of conditioned avoidance responsing (CAS) in rats was also studied. A detailed evaluation is presented of the effects of SCH 23390 and haloperidol in the Inclined Screen and CAR tests

  4. Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action

    Science.gov (United States)

    Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

    2018-03-01

    Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC50 and EC50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature.

  5. Structure modification and functionality of whey proteins: quantitative structure-activity relationship approach.

    Science.gov (United States)

    Nakai, S; Li-Chan, E

    1985-10-01

    According to the original idea of quantitative structure-activity relationship, electric, hydrophobic, and structural parameters should be taken into consideration for elucidating functionality. Changes in these parameters are reflected in the property of protein solubility upon modification of whey proteins by heating. Although solubility is itself a functional property, it has been utilized to explain other functionalities of proteins. However, better correlations were obtained when hydrophobic parameters of the proteins were used in conjunction with solubility. Various treatments reported in the literature were applied to whey protein concentrate in an attempt to obtain whipping and gelling properties similar to those of egg white. Mapping simplex optimization was used to search for the best results. Improvement in whipping properties by pepsin hydrolysis may have been due to higher protein solubility, and good gelling properties resulting from polyphosphate treatment may have been due to an increase in exposable hydrophobicity. However, the results of angel food cake making were still unsatisfactory.

  6. Stimulation of Orobanche ramosa seed germination by fusicoccin derivatives: a structure-activity relationship study.

    Science.gov (United States)

    Evidente, Antonio; Andolfi, Anna; Fiore, Michele; Boari, Angela; Vurro, Maurizio

    2006-01-01

    A structure-activity relationship study was conducted assaying 25 natural analogues and derivatives of fusicoccin (FC), and cotylenol, the aglycone of cotylenins, for their ability to stimulate the seed germination of the parasitic species Orobanche ramosa. Some of the compounds tested proved to be highly active, being 8,9-isopropylidene of the corresponding FC aglycone and the dideacetyl derivative the most active FC derivatives. In both groups of glucosides and aglycones (including cotylenol), the most important structural feature to impart activity appears to be the presence of the primary hydroxy group at C-19. Furthermore, the functionalities and the conformation of the carbotricyclic ring proved to play a significant role. The dideacetyl derivative of FC, being easily and rapidly obtainable in high yield starting by FC, could be of interest for its practical application as a stimulant of Orobanche ramosa seed germination, inducing the "suicidal germination", an interesting approach for parasitic plant management.

  7. Antimalarial benzoheterocyclic 4-aminoquinolines: Structure-activity relationship, in vivo evaluation, mechanistic and bioactivation studies.

    Science.gov (United States)

    Ongarora, Dennis S B; Strydom, Natasha; Wicht, Kathryn; Njoroge, Mathew; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Jurva, Ulrik; Masimirembwa, Collen M; Chibale, Kelly

    2015-09-01

    A novel class of benzoheterocyclic analogues of amodiaquine designed to avoid toxic reactive metabolite formation was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant) and NF54 (sensitive) strains of the malaria parasite Plasmodium falciparum. Structure-activity relationship studies led to the identification of highly promising analogues, the most potent of which had IC50s in the nanomolar range against both strains. The compounds further demonstrated good in vitro microsomal metabolic stability while those subjected to in vivo pharmacokinetic studies had desirable pharmacokinetic profiles. In vivo antimalarial efficacy in Plasmodium berghei infected mice was evaluated for four compounds, all of which showed good activity following oral administration. In particular, compound 19 completely cured treated mice at a low multiple dose of 4×10mg/kg. Mechanistic and bioactivation studies suggest hemozoin formation inhibition and a low likelihood of forming quinone-imine reactive metabolites, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. QUANTITATIVE ELECTRONIC STRUCTURE - ACTIVITY RELATIONSHIP OF ANTIMALARIAL COMPOUND OF ARTEMISININ DERIVATIVES USING PRINCIPAL COMPONENT REGRESSION APPROACH

    Directory of Open Access Journals (Sweden)

    Paul Robert Martin Werfette

    2010-06-01

    Full Text Available Analysis of quantitative structure - activity relationship (QSAR for a series of antimalarial compound artemisinin derivatives has been done using principal component regression. The descriptors for QSAR study were representation of electronic structure i.e. atomic net charges of the artemisinin skeleton calculated by AM1 semi-empirical method. The antimalarial activity of the compound was expressed in log 1/IC50 which is an experimental data. The main purpose of the principal component analysis approach is to transform a large data set of atomic net charges to simplify into a data set which known as latent variables. The best QSAR equation to analyze of log 1/IC50 can be obtained from the regression method as a linear function of several latent variables i.e. x1, x2, x3, x4 and x5. The best QSAR model is expressed in the following equation,  (;;   Keywords: QSAR, antimalarial, artemisinin, principal component regression

  9. Applications of genetic algorithms on the structure-activity relationship analysis of some cinnamamides.

    Science.gov (United States)

    Hou, T J; Wang, J M; Liao, N; Xu, X J

    1999-01-01

    Quantitative structure-activity relationships (QSARs) for 35 cinnamamides were studied. By using a genetic algorithm (GA), a group of multiple regression models with high fitness scores was generated. From the statistical analyses of the descriptors used in the evolution procedure, the principal features affecting the anticonvulsant activity were found. The significant descriptors include the partition coefficient, the molar refraction, the Hammet sigma constant of the substituents on the benzene ring, and the formation energy of the molecules. It could be found that the steric complementarity and the hydrophobic interaction between the inhibitors and the receptor were very important to the biological activity, while the contribution of the electronic effect was not so obvious. Moreover, by construction of the spline models for these four principal descriptors, the effective range for each descriptor was identified.

  10. Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues.

    Science.gov (United States)

    Van Baelen, Gitte; Hostyn, Steven; Dhooghe, Liene; Tapolcsányi, Pál; Mátyus, Péter; Lemière, Guy; Dommisse, Roger; Kaiser, Marcel; Brun, Reto; Cos, Paul; Maes, Louis; Hajós, György; Riedl, Zsuzsanna; Nagy, Ildikó; Maes, Bert U W; Pieters, Luc

    2009-10-15

    Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-beta-carboline, showed the best in vitro activity, with an IC(50) value of 0.45 microM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI>1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure-activity relationships are discussed and compared with related naturally occurring compounds.

  11. Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

    Science.gov (United States)

    Littleson, Mairi M; Baker, Christopher M; Dalençon, Anne J; Frye, Elizabeth C; Jamieson, Craig; Kennedy, Alan R; Ling, Kenneth B; McLachlan, Matthew M; Montgomery, Mark G; Russell, Claire J; Watson, Allan J B

    2018-03-16

    Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure-activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.

  12. STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF DITERPENES FOR TREATMENT OF ALZHEIMER'S DISEASE

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    Gabriel F. dos Santos

    Full Text Available Alzheimer's disease is an irreversible, degenerative and age-related disease which is growing more and more with the increase in life expectancy. Kaurane diterpenes are a class of natural products available in large amounts in nature and isolated from plants grown worldwide. In the present work¸ twenty-seven kaurane diterpenes of natural origin and some readily available derivatives were assayed for acetylcholinesterase inhibition and the structure-activity relationship was analyzed. The kaurenoic acid derivatives screened showed to be promising inhibitors of AChE, which could provide new leads for drugs to fight Alzheimer's disease symptoms. Among them, eleven compounds showed activities comparable or higher than the positive control galantamine. Existence of an allylic hydroxyl group showed to be an important structural feature for AChE inhibition. In addition, presence of free hydroxyl groups at C-17 and C-19, furnished a diol especially active, able to completely inhibit AChE.

  13. A Quantitative Structure-Activity Relationships (QSAR Study of Piperine Based Derivatives with Leishmanicidal Activity

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    Edilson Beserra Alencar Filho

    2017-04-01

    Full Text Available Leishmaniasis is a parasitic disease which represents a serious public health problem in developing countries. It is considered a neglected tropical disease, for which there is little initiative in the search for therapeutic alternatives by pharmaceutical industry. Natural products remain a great source of inspiration for obtaining bioactive molecules. In 2010, Singh and co-workers published the synthesis and in vitro biological activity of piperoyl-aminoacid conjugates, as well as of piperine, against cellular cultures of Leishmania donovani. The piperine is an alkaloid isolated from Piper nigrum that has many activities described in the literature. In this work, we present a Quantitative Structure-Activity Study of piperine derivatives tested by Singh and co-workers, aiming to highlight important molecular features for leishmanicidal activity, obtaining a mathematical model to predict the activity of new analogs. Compounds were submitted to a geometry optimization computational procedure at semiempirical level of quantum theory. Molecular descriptors for the set of compounds were calculated by E-Dragon online plataform, followed by a variable selection procedure using Ordered Predictors Selection algorithm. Validation parameters obtained showed that a good QSAR model, based on multiple linear regression, was obtained (R2 = 0.85; Q2 = 0.69, and the following conclusions regarding the structure-activity relationship were elucidated: Compounds with electronegative atoms on different substituent groups of analogs, absence of unsaturation on lateral chain, presence of ester instead of carboxyl, and large volumes (due the presence of additional aromatic rings trends to increase the activity against promastigote forms of leishmania. DOI: http://dx.doi.org/10.17807/orbital.v9i1.893

  14. Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors.

    Science.gov (United States)

    Nargotra, Amit; Sharma, Sujata; Koul, Jawahir Lal; Sangwan, Pyare Lal; Khan, Inshad Ali; Kumar, Ashwani; Taneja, Subhash Chander; Koul, Surrinder

    2009-10-01

    Quantitative structure activity relationship (QSAR) analysis of piperine analogs as inhibitors of efflux pump NorA from Staphylococcus aureus has been performed in order to obtain a highly accurate model enabling prediction of inhibition of S. aureus NorA of new chemical entities from natural sources as well as synthetic ones. Algorithm based on genetic function approximation method of variable selection in Cerius2 was used to generate the model. Among several types of descriptors viz., topological, spatial, thermodynamic, information content and E-state indices that were considered in generating the QSAR model, three descriptors such as partial negative surface area of the compounds, area of the molecular shadow in the XZ plane and heat of formation of the molecules resulted in a statistically significant model with r(2)=0.962 and cross-validation parameter q(2)=0.917. The validation of the QSAR models was done by cross-validation, leave-25%-out and external test set prediction. The theoretical approach indicates that the increase in the exposed partial negative surface area increases the inhibitory activity of the compound against NorA whereas the area of the molecular shadow in the XZ plane is inversely proportional to the inhibitory activity. This model also explains the relationship of the heat of formation of the compound with the inhibitory activity. The model is not only able to predict the activity of new compounds but also explains the important regions in the molecules in quantitative manner.

  15. Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

    Science.gov (United States)

    Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

    2008-01-01

    Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

  16. Quantitative structure-activity relationship (QSAR) for insecticides: development of predictive in vivo insecticide activity models.

    Science.gov (United States)

    Naik, P K; Singh, T; Singh, H

    2009-07-01

    Quantitative structure-activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r(2) values of 0.949 and 0.838 as well as [image omitted] values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD(50) values for the test set data with r(2) of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.

  17. Molecular Descriptors Family on Structure Activity Relationships 2. Insecticidal Activity of Neonicotinoid Compounds

    Directory of Open Access Journals (Sweden)

    Sorana BOLBOACĂ

    2005-01-01

    Full Text Available The neonicotinoids are the newest major class of insecticides modeled after the basic nicotine molecule having improved insecticide activity and generally low toxicity. The insecticidal activities of neonicotinoids were previous studied using 3D and standard partial least squares regression models. The paper describes the ability of the MDF SAR methodology in prediction of insecticidal activities of neonicotinoid compounds. The best MDF SAR bi-varied model was validated on training and test sets and its ability on prediction of insecticidal activity was compared with previous reported models. Even if the MDF SAR methodology is complex and time consuming the results worth the effort because they are statistical significant better then previous reported results.

  18. 1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies.

    Science.gov (United States)

    La Regina, Giuseppe; D'Auria, Felicia Diodata; Tafi, Andrea; Piscitelli, Francesco; Olla, Stefania; Caporuscio, Fabiana; Nencioni, Lucia; Cirilli, Roberto; La Torre, Francesco; De Melo, Nadja Rodrigues; Kelly, Steven L; Lamb, David C; Artico, Marino; Botta, Maurizio; Palamara, Anna Teresa; Silvestri, Romano

    2008-07-10

    New 1-[(3-aryloxy-3-aryl)propyl]-1 H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure-activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketoconazole, miconazole, and econazole, and were more potent than fluconazole. Several derivatives ( 10, 12, 14, 18- 20, 24, 28, 29, 30, and 34) turned out to be potent inhibitors of C. albicans strains resistant to fluconazole, with MIC values less than 10 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC SARs of imidazoles 10- 44 were rationalized with reasonable accuracy by a previously developed quantitative pharmacophore for antifungal agents.

  19. Anticancer and reversing multidrug resistance activities of natural isoquinoline alkaloids and their structure-activity relationship.

    Science.gov (United States)

    Qing, Zhi-Xing; Huang, Jia-Lu; Yang, Xue-Yi; Liu, Jing-Hong; Cao, Hua-Liang; Xiang, Feng; Cheng, Pi; Zeng, Jian-Guo

    2017-09-20

    The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloid (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Flavonoids as Vasorelaxant Agents: Synthesis, Biological Evaluation and Quantitative Structure Activities Relationship (QSAR Studies

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    Yongzhou Hu

    2011-09-01

    Full Text Available A series of 2-(2-diethylamino-ethoxychalcone and 6-prenyl(or its isomers-flavanones 10a,b and 11a–g were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pretreated with 1 μM phenylephrine (PE. Several compounds showed potent vasorelaxant activities. Compound 10a (EC50 = 7.6 μM, Emax = 93.1%, the most potent one, would be a promising structural template for development of novel and more efficient vasodilators. Further, 2D-QSAR analysis of compounds 10a,b and 11c-e as well as thirty previously synthesized flavonoids 1-3 and 12-38 using Enhanced Replacement Method-Multiple Linear Regression (ERM-MLR was further performed based on an optimal set of molecular descriptors (H5m, SIC2, DISPe, Mor03u and L3m, leading to a reliable model with good predictive ability (Rtrain2 = 0.839, Qloo2 = 0.733 and Rtest2 = 0.804. The results provide good insights into the structure- activity relationships of the target compounds.

  1. Structure-activity relationship of a u-type antimicrobial microemulsion system.

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    Full Text Available The structure-activity relationship of a U-type antimicrobial microemulsion system containing glycerol monolaurate and ethanol at a 1∶1 mass ratio as oil phase and Tween 20 as surfactant were investigated along a water dilution line at a ratio of 80∶20 mass% surfactant/oil phase, based on a pseudo-ternary phase diagram. The differential scanning calorimetry results showed that in the region of up to 33% water, all water molecules are confined to the hydrophilic core of the reverse micelles, leading to the formation of w/o microemulsion. As the water content increases, the water gains mobility, and transforms into bicontinuous in the region of 33-39% water, and finally the microemulsion become o/w in the region of above 39% water. The microstructure characterization was confirmed by the dynamic light scattering measurements and freeze-fracture transmission electron microscope observation. The antimicrobial activity assay using kinetics of killing analysis demonstrated that the microemulsions in w/o regions exhibited relatively high antimicrobial activity against Escherichia coli and Staphylococcus aureus due to the antimicrobial oil phase as the continuous phase, while the antimicrobial activity started to decrease when the microemulsions entered the bicontinuous region, and decreased rapidly as the water content increased in the o/w region, as a result of the dilution of antimicrobial oil droplets in the aqueous continuous phase.

  2. The uridine diphosphate glucuronosyltransferases: quantitative structure-activity relationships for hydroxyl polychlorinated biphenyl substrates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Degao [Dalian University of Technology, Department of Environmental Science and Technology, Dalian (China)

    2005-10-01

    Quantitative structure-activity relationships (QSARs), which relate the glucuronidation of hydroxyl polychlorinated biphenyls (OH-PCBs) - catalyzed by the uridine diphosphate glucuronosyltransferases (UGTs) - to their physicochemical properties and molecular structural parameters, can be used to predict the rate constants and interpret the mechanism of glucuronidation. In this study, QSARs have been developed that use 23 semi-empirical calculated quantum chemical descriptors to predict the logarithms of the constants 1/K{sub m} and V{sub max}, related to enzyme kinetics. A partial least squares regression method was used to select the optimal set of descriptors to minimize the multicollinearity between the descriptors, as well as to maximize the cross-validated coefficient (Q{sup 2} {sub cum}) values. The key descriptors affecting log(1/K{sub m}) were E{sub lumo}- E{sub homo} (the energy gap between the lowest unoccupied molecular orbital and the highest occupied molecular orbital) and q{sub C}{sup -} (the largest negative net atomic charge on a carbon atom), while the key descriptors affecting log V{sub max} were the polarizability {alpha}, the Connolly solvent-excluded volume (CSEV), and logP (the logarithm of the partition coefficient for octanol/water). From the results obtained it can be concluded that hydrophobic and electronic aspects of OH-PCBs are important in the glucuronidation of OH-PCBs. (orig.)

  3. Quantitative Structure--Activity Relationship (QSAR) for the Oxidation of Trace Organic Contaminants by Sulfate Radical.

    Science.gov (United States)

    Xiao, Ruiyang; Ye, Tiantian; Wei, Zongsu; Luo, Shuang; Yang, Zhihui; Spinney, Richard

    2015-11-17

    The sulfate radical anion (SO4•–) based oxidation of trace organic contaminants (TrOCs) has recently received great attention due to its high reactivity and low selectivity. In this study, a meta-analysis was conducted to better understand the role of functional groups on the reactivity between SO4•– and TrOCs. The results indicate that compounds in which electron transfer and addition channels dominate tend to exhibit a faster second-order rate constants (kSO4•–) than that of H–atom abstraction, corroborating the SO4•– reactivity and mechanisms observed in the individual studies. Then, a quantitative structure activity relationship (QSAR) model was developed using a sequential approach with constitutional, geometrical, electrostatic, and quantum chemical descriptors. Two descriptors, ELUMO and EHOMO energy gap (ELUMO–EHOMO) and the ratio of oxygen atoms to carbon atoms (#O:C), were found to mechanistically and statistically affect kSO4•– to a great extent with the standardized QSAR model: ln kSO4•– = 26.8–3.97 × #O:C – 0.746 × (ELUMO–EHOMO). In addition, the correlation analysis indicates that there is no dominant reaction channel for SO4•– reactions with various structurally diverse compounds. Our QSAR model provides a robust predictive tool for estimating emerging micropollutants removal using SO4•– during wastewater treatment processes.

  4. Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction.

    Science.gov (United States)

    De Filippis, Vincenzo; Acquasaliente, Laura; Pontarollo, Giulia; Peterle, Daniele

    2018-01-01

    The advent of recombinant DNA technology allowed to site-specifically insert, delete, or mutate almost any amino acid in a given protein, significantly improving our knowledge of protein structure, stability, and function. Nevertheless, a quantitative description of the physical and chemical basis that makes a polypeptide chain to efficiently fold into a stable and functionally active conformation is still elusive. This mainly originates from the fact that nature combined, in a yet unknown manner, different properties (i.e., hydrophobicity, conformational propensity, polarizability, and hydrogen bonding capability) into the 20 standard natural amino acids, thus making difficult, if not impossible, to univocally relate the change in protein stability or function to the alteration of physicochemical properties caused by amino acid exchange(s). In this view, incorporation of noncoded amino acids with tailored side chains, allowing to finely tune the structure at a protein site, would facilitate to dissect the effects of a given mutation in terms of one or a few physicochemical properties, thus much expanding the scope of physical organic chemistry in the study of proteins. In this review, relevant applications from our laboratory will be presented on the use of noncoded amino acids in structure-activity relationships studies of hirudin binding to thrombin. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  5. Structure-activity relationships and molecular docking of thirteen synthesized flavonoids as horseradish peroxidase inhibitors.

    Science.gov (United States)

    Mahfoudi, Reguia; Djeridane, Amar; Benarous, Khedidja; Gaydou, Emile M; Yousfi, Mohamed

    2017-10-01

    For the first time, the structure-activity relationships of thirteen synthesized flavonoids have been investigated by evaluating their ability to modulate horseradish peroxidase (HRP) catalytic activity. Indeed, a modified spectrophotometrically method was carried out and optimized using 4-methylcatechol (4-MC) as peroxidase co-substrate. The results show that these flavonoids exhibit a great capacity to inhibit peroxidase with Ki values ranged from 0.14±0.01 to 65±0.04mM. Molecular docking has been achieved using Auto Dock Vina program to discuss the nature of interactions and the mechanism of inhibition. According to the docking results, all the flavonoids have shown great binding affinity to peroxidase. These molecular modeling studies suggested that pyran-4-one cycle acts as an inhibition key for peroxidase. Therefore, potent peroxidase inhibitors are flavonoids with these structural requirements: the presence of the hydroxyl (OH) group in 7, 5 and 4' positions and the absence of the methoxy (O-CH 3 ) group. Apigenin contributed better in HRP inhibitory activity. The present study has shown that the studied flavonoids could be promising HRP inhibitors, which can help in developing new molecules to control thyroid diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Quantitative Structure activity relationship and risk analysis of some pesticides in the cattle milk

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    Faqir Muhammad*, Ijaz Javed, Masood Akhtar1, Zia-ur-Rahman, Mian Muhammad Awais1, Muhammad Kashif Saleemi2 and Muhammad Irfan Anwar3

    2012-10-01

    Full Text Available Milk of cattle was collected from various localities of Faisalabad, Pakistan. Pesticides concentration was determined by HPLC using solid phase microextraction. The residue analysis revealed that about 40% milk samples were contaminated with pesticides. The mean±SE levels (ppm of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.38±0.02, 0.26±0.02, 0.072±0.01 and 0.085±0.02, respectively. Quantitative structure activity relationship (QSAR models were used to predict the residues of unknown pesticides in the milk of cattle using their known physicochemical properties such as molecular weight (MW, melting point (MP, and log octanol to water partition coefficient (Ko/w as well as the milk characteristics such as pH, % fat, and specific gravity (SG in this species. The analysis revealed good correlation coefficients (R2 = 0.91 for cattle QSAR model. The coefficient for Ko/w for the studied pesticides was higher in cattle milk. Risk analysis was conducted based upon the determined pesticide residues and their provisional tolerable daily intakes. The daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study were 3, 11, 2.5 times higher, respectively in cattle milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

  7. Red Wine Tannin Structure-Activity Relationships during Fermentation and Maceration.

    Science.gov (United States)

    Yacco, Ralph S; Watrelot, Aude A; Kennedy, James A

    2016-02-03

    The correlation between tannin structure and corresponding activity was investigated by measuring the thermodynamics of interaction between tannins isolated from commercial red wine fermentations and a polystyrene divinylbenzene HPLC column. Must and/or wine samples were collected throughout fermentation/maceration from five Napa Valley wineries. By varying winery, fruit source, maceration time, and cap management practice, it was considered that a reasonably large variation in commercially relevant tannin structure would result. Tannins were isolated from samples collected using low pressure chromatography and were then characterized by gel permeation chromatography and acid-catalyzed cleavage in the presence of excess phloroglucinol (phloroglucinolysis). Corresponding tannin activity was determined using HPLC by measuring the thermodynamics of interaction between isolated tannin and a polystyrene divinylbenzene HPLC column. This measurement approach was designed to determine the ability of tannins to hydrophobically interact with a hydrophobic surface. The results of this study indicate that tannin activity is primarily driven by molecular size. Compositionally, tannin activity was positively associated with seed tannins and negatively associated with skin and pigmented tannins. Although measured indirectly, the extent of tannin oxidation as determined by phloroglucinolysis conversion yield suggests that tannin oxidation at this stage of production reduces tannin activity. Based upon maceration time, this study indicates that observed increases in perceived astringency quality, if related to tannin chemistry, are driven by tannin molecular mass as opposed to pigmented tannin formation or oxidation. Overall, the results of this study give new insight into tannin structure-activity relationships which dominate during extraction.

  8. The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity

    Science.gov (United States)

    Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

    2015-01-01

    In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. PMID:26712768

  9. Structure-Activity Relationship Analysis of 3-phenylcoumarin-Based Monoamine Oxidase B Inhibitors

    Science.gov (United States)

    Rauhamäki, Sanna; Postila, Pekka A.; Niinivehmas, Sanna; Kortet, Sami; Schildt, Emmi; Pasanen, Mira; Manivannan, Elangovan; Ahinko, Mira; Koskimies, Pasi; Nyberg, Niina; Huuskonen, Pasi; Multamäki, Elina; Pasanen, Markku; Juvonen, Risto O.; Raunio, Hannu; Huuskonen, Juhani; Pentikäinen, Olli T.

    2018-03-01

    Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson’s disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM - 1 µM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activity relationship analysis summarizes the atom-level determinants of the MAO-B inhibition by the derivatives. Finally, the cross-reactivity of the derivatives was tested against monoamine oxidase A and a specific subset of enzymes linked to estradiol metabolism, known to have coumarin-based inhibitors. Overall, the results indicate that the 3-phenylcoumarins, especially derivative 1, present unique pharmacological features worth considering in future drug development.

  10. Deciphering structure-activity relationships in a series of Tat/TAR inhibitors.

    Science.gov (United States)

    Pascale, Lise; González, Alejandro López; Di Giorgio, Audrey; Gaysinski, Marc; Teixido Closa, Jordi; Tejedor, Roger Estrada; Azoulay, Stéphane; Patino, Nadia

    2016-11-01

    A series of pentameric "Polyamide Amino Acids" (PAAs) compounds derived from the same trimeric precursor have been synthesized and investigated as HIV TAR RNA ligands, in the absence and in the presence of a Tat fragment. All PAAs bind TAR with similar sub-micromolar affinities but their ability to compete efficiently with the Tat fragment strongly differs, IC50 ranging from 35 nM to >2 μM. While NMR and CD studies reveal that all PAA interact with TAR at the same site and induce globally the same RNA conformational change upon binding, a comparative thermodynamic study of PAA/TAR equilibria highlights distinct TAR binding modes for Tat competitor and non-competitor PAAs. This led us to suggest two distinct interaction modes that have been further validated by molecular modeling studies. While the binding of Tat competitor PAAs induces a contraction at the TAR bulge region, the binding of non-competitor ones widens it. This could account for the distinct PAA ability to compete with Tat fragment. Our work illustrates how comparative thermodynamic studies of a series of RNA ligands of same chemical family are of value for understanding their binding modes and for rationalizing structure-activity relationships.

  11. Attraction Pheromone of The Benthic Diatom Seminavis robusta: Studies on Structure-Activity Relationships.

    Science.gov (United States)

    Lembke, Christine; Stettin, Daniel; Speck, Franziska; Ueberschaar, Nico; De Decker, Sam; Vyverman, Wim; Pohnert, Georg

    2018-04-01

    Recently the first pheromone of a marine diatom was identified to be the diketopiperazine (S,S)-diproline. This compound facilitates attraction between mating partners in the benthic diatom Seminavis robusta. Interestingly, sexualized S. robusta cells are attracted to both the natural pheromone (S,S)-diproline as well as to its enantiomer (R,R)-diproline. Usually stereospecificity is a prerequisite for successful substrate-receptor interactions, and especially pheromone perception is often highly enantioselective. Here we introduce a structure-activity relationship study, to learn more about the principles of pheromone reception in diatoms. We analyzed the activity of nine different diketopiperazines in attraction and interference assays. The pheromone diproline itself, as well as a pipecolic acid derived diketopiperazine with two expanded aliphatic ring systems, showed the highest attractivity. Hydroxylatoin of the aliphatic rings abolished any bioactivity. Diketopiperazines derived from acyclic amino acids were not attrative as well. All stereoisomers of both the diproline and the pipecolic acid derived diketopiperazine were purified by enantioselective high-performance liquid chromatography, and application in bioactivity tests confirmed that attraction pheromone perception in this diatom is indeed not stereospecific. However, the lack of activity of diketopiperazines derived from acyclic amino acids suggests a specificity that prevents misguidance to sources of other naturally occurring diketopiperazines.

  12. Antiproliferative terpenoids from almond hulls (Prunus dulcis): identification and structure-activity relationships.

    Science.gov (United States)

    Amico, Vincenzo; Barresi, Vincenza; Condorelli, Daniele; Spatafora, Carmela; Tringali, Corrado

    2006-02-08

    Bioassay-guided fractionation of the EtOAc crude extract from Sicilian almond hulls, a waste material from Prunus dulcis crop, allowed identification of 10 constituents, isolated as pure compounds (1-5, 7, and 10) or unseparable mixtures (5 + 6 and 8 + 9). All compounds were subjected to spectroscopic analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide bioassay on MCF-7 human breast cancer cells. In addition to the main components oleanolic (1), ursolic (2), and betulinic (3) acids, the 2-hydroxy analogues alphitolic (4), corosolic (5), and maslinic (6) acids, as well as the related aldehydes, namely, betulinic (7), oleanolic (8), and ursolic (9), were identified. From a more polar fraction, the beta-sitosterol 3-O-glucoside (10) was also identified. A sample of commercially available betulin (11) was also included in bioassays as further support to a structure-activity relationship study. Betulinic acid showed antiproliferative activity toward MCF-7 cells (GI50 = 0.27 microM), higher than the anticancer drug 5-fluorouracil.

  13. Compound toxicity screening and structure-activity relationship modeling in Escherichia coli.

    Science.gov (United States)

    Planson, Anne-Gaëlle; Carbonell, Pablo; Paillard, Elodie; Pollet, Nicolas; Faulon, Jean-Loup

    2012-03-01

    Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/∼faulon/EcoliTox.php). Copyright © 2011 Wiley Periodicals, Inc.

  14. Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout.

    Science.gov (United States)

    Mendenhall, Jeffrey; Meiler, Jens

    2016-02-01

    Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods.

  15. Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

    Science.gov (United States)

    Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik

    2017-07-01

    After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural diverse polymers which are capable to estimate green algae growth inhibition (EC50). The model (N = 43, R 2  = 0.73, RMSE = 0.28) is a regression-based decision tree using one structural descriptor for each of three polymer classes separated based on charge. The QSAR is applicable to linear homo polymers as well as copolymers and does not require information on the size of the polymer particle or underlying core material. Highly branched polymers, non-nitrogen cationic polymers and polymeric surfactants are not included in the model and thus cannot be evaluated. The model works best for cationic and non-ionic polymers for which cellular adsorption, disruption of the cell wall and photosynthesis inhibition were the mechanisms of action. For anionic polymers, specific properties of the polymer and test characteristics need to be known for detailed assessment. The data and QSAR results for anionic polymers, when combined with molecular dynamics simulations indicated that nutrient depletion is likely the dominant mode of toxicity. Nutrient depletion in turn, is determined by the non-linear interplay between polymer charge density and backbone flexibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 6-Nitrobenzimidazole derivatives: potential phosphodiesterase inhibitors: synthesis and structure-activity relationship.

    Science.gov (United States)

    Khan, K M; Shah, Zarbad; Ahmad, V U; Ambreen, N; Khan, M; Taha, M; Rahim, F; Noreen, S; Perveen, S; Choudhary, M I; Voelter, W

    2012-02-15

    6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 μM. Compounds 30 (IC(50)=1.5±0.043 μM), 1 (IC(50)=2.4±0.049 μM), 11 (IC(50)=5.7±0.113 μM), 13 (IC(50)=6.4±0.148 μM), 14 (IC(50)=10.5±0.51 μM), 9 (IC(50)=11.49±0.08 μM), 3 (IC(50)=63.1±1.48 μM), 10 (IC(50)=120.0±4.47 μM), and 6 (IC(50)=153.2±5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Cytotoxic constituents of propolis from Myanmar and their structure-activity relationship.

    Science.gov (United States)

    Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

    2009-12-01

    Thirteen cycloartane-type tritepenes (1-13) and four prenylated flavanones (14-17) isolated from propolis collected in Myanmar, were evaluated for their cytotoxic activity against a panel of six different cancer cell lines; three murine cancer cell lines (colon 26-L5 carcinoma, B16-BL6 melanoma, and Lewis lung carcinoma) and three human cancer cell lines (lung A549 adenocarcinoma, cervix HeLa adenocarcinoma and HT-1080 fibrosarcoma). Among them, a cycloartane-type triterpene, 3alpha,27-dihydroxycycloart-24E-en-26-oic acid (3), showed the most potent cytotoxicity against B16-BL6 cells with an IC(50) value of 5.91 microM, comparable to those of positive controls, doxorubicin (IC(50), 5.66 microM) and 5-fluorouracil (IC(50), 4.88 microM). In addition, (2S)-5,7-dihydroxy-4'-methoxy-8,3'-diprenylflavanone (14) exhibited strong cytotoxicity against all the tested cancer cell lines with the IC(50) values ranging from 14.0 to 26.4 microM. Based on the observed results, the structure-activity relationships are discussed.

  18. Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship.

    Science.gov (United States)

    Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

    2008-05-15

    Several classes of flavonoids [flavanoids (1-10), flavonol (11), isoflavones (12-18), isoflavanones (19-22), isoflavans (23-26), chalcones (27-30), auronol (31), pterocarpans (32-37), 2-arylbenzofuran (38), and neoflavonoid (39)] and lignans (40-42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080 fibrosarcoma cell lines. Based on the observed results, structure-activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxyflavanone (3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66microM), LLC (IC(50), 9.29microM), A549 (IC(50), 8.63microM), and HT-1080 (IC(50), 7.94microM) cancer cell lines, and mucronulatol (26) against LLC (IC(50), 8.38microM) and A549 (IC(50), 9.9microM) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development.

  19. Structure-Activity Relationships for Rates of Aromatic Amine Oxidation by Manganese Dioxide.

    Science.gov (United States)

    Salter-Blanc, Alexandra J; Bylaska, Eric J; Lyon, Molly A; Ness, Stuart C; Tratnyek, Paul G

    2016-05-17

    New energetic compounds are designed to minimize their potential environmental impacts, which includes their transformation and the fate and effects of their transformation products. The nitro groups of energetic compounds are readily reduced to amines, and the resulting aromatic amines are subject to oxidation and coupling reactions. Manganese dioxide (MnO2) is a common environmental oxidant and model system for kinetic studies of aromatic amine oxidation. In this study, a training set of new and previously reported kinetic data for the oxidation of model and energetic-derived aromatic amines was assembled and subjected to correlation analysis against descriptor variables that ranged from general purpose [Hammett σ constants (σ(-)), pKas of the amines, and energies of the highest occupied molecular orbital (EHOMO)] to specific for the likely rate-limiting step [one-electron oxidation potentials (Eox)]. The selection of calculated descriptors (pKa, EHOMO, and Eox) was based on validation with experimental data. All of the correlations gave satisfactory quantitative structure-activity relationships (QSARs), but they improved with the specificity of the descriptor. The scope of correlation analysis was extended beyond MnO2 to include literature data on aromatic amine oxidation by other environmentally relevant oxidants (ozone, chlorine dioxide, and phosphate and carbonate radicals) by correlating relative rate constants (normalized to 4-chloroaniline) to EHOMO (calculated with a modest level of theory).

  20. Structure-Activity Relationships for Rates of Aromatic Amine Oxidation by Manganese Dioxide

    International Nuclear Information System (INIS)

    Salter-Blanc, Alexandra J.; Lyon, Molly A.; Science University, Portland, OR; Ness, Stuart C.; Science University, Portland, OR; Tratnyek, Paul G.; Science University, Portland, OR

    2016-01-01

    New energetic compounds are designed to minimize their potential environmental impacts, which includes their transformation and the fate and effects of their transformation products. The nitro groups of energetic compounds are readily reduced to amines, and the resulting aromatic amines are subject to oxidation and coupling reactions. Manganese dioxide (MnO 2 ) is a common environmental oxidant and model system for kinetic studies of aromatic amine oxidation. Here in this study, a training set of new and previously reported kinetic data for the oxidation of model and energetic-derived aromatic amines was assembled and subjected to correlation analysis against descriptor variables that ranged from general purpose [Hammett σ constants (σ − ), pK a s of the amines, and energies of the highest occupied molecular orbital (E HOMO )] to specific for the likely rate-limiting step [one-electron oxidation potentials (E ox )]. The selection of calculated descriptors (pK a ), E HOMO , and E ox ) was based on validation with experimental data. All of the correlations gave satisfactory quantitative structure-activity relationships (QSARs), but they improved with the specificity of the descriptor. The scope of correlation analysis was extended beyond MnO 2 to include literature data on aromatic amine oxidation by other environmentally relevant oxidants (ozone, chlorine dioxide, and phosphate and carbonate radicals) by correlating relative rate constants (normalized to 4-chloroaniline) to E HOMO (calculated with a modest level of theory).

  1. Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

    Science.gov (United States)

    Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

    1998-01-15

    We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

  2. Deep neural nets as a method for quantitative structure-activity relationships.

    Science.gov (United States)

    Ma, Junshui; Sheridan, Robert P; Liaw, Andy; Dahl, George E; Svetnik, Vladimir

    2015-02-23

    Neural networks were widely used for quantitative structure-activity relationships (QSAR) in the 1990s. Because of various practical issues (e.g., slow on large problems, difficult to train, prone to overfitting, etc.), they were superseded by more robust methods like support vector machine (SVM) and random forest (RF), which arose in the early 2000s. The last 10 years has witnessed a revival of neural networks in the machine learning community thanks to new methods for preventing overfitting, more efficient training algorithms, and advancements in computer hardware. In particular, deep neural nets (DNNs), i.e. neural nets with more than one hidden layer, have found great successes in many applications, such as computer vision and natural language processing. Here we show that DNNs can routinely make better prospective predictions than RF on a set of large diverse QSAR data sets that are taken from Merck's drug discovery effort. The number of adjustable parameters needed for DNNs is fairly large, but our results show that it is not necessary to optimize them for individual data sets, and a single set of recommended parameters can achieve better performance than RF for most of the data sets we studied. The usefulness of the parameters is demonstrated on additional data sets not used in the calibration. Although training DNNs is still computationally intensive, using graphical processing units (GPUs) can make this issue manageable.

  3. Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396.

    Science.gov (United States)

    Murgatroyd, Christopher; Pirrie, Lisa; Tran, Fanny; Smith, Terry K; Westwood, Nicholas J; Adamson, Catherine S

    2016-09-15

    HIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated. Combinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they

  4. Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity

    International Nuclear Information System (INIS)

    Morales, Aliuska Helguera; Perez, Miguel Angel Cabrera; Combes, Robert D.; Gonzalez, Maykel Perez

    2006-01-01

    Several nitrocompounds have been screened for carcinogenicity in rodents, but this is a lengthy and expensive process, taking two years and typically costing 2.5 million dollars, and uses large numbers of animals. There is, therefore, much impetus to develop suitable alternative methods. One possible way of predicting carcinogenicity is to use quantitative structure-activity relationships (QSARs). QSARs have been widely utilized for toxicity testing, thereby contributing to a reduction in the need for experimental animals. This paper describes the results of applying a TOPological substructural molecular design (TOPS-MODE) approach for predicting the rodent carcinogenicity of nitrocompounds. The model described 79.10% of the experimental variance, with a standard deviation of 0.424. The predictive power of the model was validated by leave-one-out validation, with a determination coefficient of 0.666. In addition, this approach enabled the contribution of different fragments to carcinogenic potency to be assessed, thereby making the relationships between structure and carcinogenicity to be transparent. It was found that the carcinogenic activity of the chemicals analysed was increased by the presence of a primary amine group bonded to the aromatic ring, a manner that was proportional to the ring aromaticity. The nitro group bonded to an aromatic carbon atom is a more important determinant of carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the TOPS-MODE approach was compared with four other predictive models, but none of these could explain more than 66% of the variance in the carcinogenic potency with the same number of variables

  5. Evolution of the international workshops on quantitative structure-activity relationships (QSARs) in environmental toxicology.

    Science.gov (United States)

    Kaiser, K L E

    2007-01-01

    This presentation will review the evolution of the workshops from a scientific and personal perspective. From their modest beginning in 1983, the workshops have developed into larger international meetings, regularly held every two years. Their initial focus on the aquatic sphere soon expanded to include properties and effects on atmospheric and terrestrial species, including man. Concurrent with this broadening of their scientific scope, the workshops have become an important forum for the early dissemination of all aspects of qualitative and quantitative structure-activity research in ecotoxicology and human health effects. Over the last few decades, the field of quantitative structure/activity relationships (QSARs) has quickly emerged as a major scientific method in understanding the properties and effects of chemicals on the environment and human health. From substances that only affect cell membranes to those that bind strongly to a specific enzyme, QSARs provides insight into the biological effects and chemical and physical properties of substances. QSARs are useful for delineating the quantitative changes in biological effects resulting from minor but systematic variations of the structure of a compound with a specific mode of action. In addition, more holistic approaches are being devised that result in our ability to predict the effects of structurally unrelated compounds with (potentially) different modes of action. Research in QSAR environmental toxicology has led to many improvements in the manufacturing, use, and disposal of chemicals. Furthermore, it has led to national policies and international agreements, from use restrictions or outright bans of compounds, such as polychlorinated biphenyls (PCBs), mirex, and highly chlorinated pesticides (e.g. DDT, dieldrin) for the protection of avian predators, to alternatives for ozone-depleting compounds, to better waste treatment systems, to more powerful and specific acting drugs. Most of the recent advances

  6. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    Science.gov (United States)

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  7. Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents.

    Science.gov (United States)

    Gruneich, Jeffrey A; Diamond, Scott L

    2007-05-01

    The use of cholesterol-based cationic lipids and the ability of glucocorticoids to reduce local inflammatory response to lipoplexes motivated an investigation of structure-activity relationships for cationic steroids. A one-step synthetic scheme using iminothiolane was developed to link spermine to the 21-OH position of steroids via an amidine linkage. Five steroids (cortisol, dexamethasone, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone) with increasing hydrophobicity of the parent steroid (Log P(ster) from 1.51 to 3.01) were conjugated with spermine, formulated with dioleoylphosphatidylethanolamine (DOPE) at DOPE : steroid mole ratios (R) of R = 0.5 to 2, and then complexed with 1 microg enhanced green fluorescent protein (EGFP) plasmid DNA at charge ratios (CR) = 2 to 24 amines per phosphate (0.5 to 6 steroids per phosphate). The resulting 105 different formulations of the cationic steroid series were used to lipofect bovine aortic endothelial cells. Transgene expression data at either 24 or 48 h post-lipofection for all formulations was collapsed onto master curves when plotted against a single empirical dimensionless parameter, the lipofection index (LI) = CR (Log P(liposome))(Log P(ster)/|DeltaLog P|) [R/(R + 1)] where DeltaLog P = Log P(DOPE)- Log P(ster) and Log P(liposome) is a mole-weighted average of the DOPE/cationic steroid liposome hydrophobicity. For 7 lipofection increased linearly with LI (EGFP approximately 0 for LI 29, thus providing a predictive design rule based on Log P of the hydrophobic moiety of the cationic steroid lipid. Copyright (c) 2007 John Wiley & Sons, Ltd.

  8. Quantitative structure activity relationship and risk analysis of some pesticides in the goat milk.

    Science.gov (United States)

    Muhammad, Faqir; Awais, Mian Muhammad; Akhtar, Masood; Anwar, Muhammad Irfan

    2013-01-04

    The detection and quantification of different pesticides in the goat milk samples collected from different localities of Faisalabad, Pakistan was performed by HPLC using solid phase microextraction. The analysis showed that about 50% milk samples were contaminated with pesticides. The mean±SEM levels (ppm) of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.34±0.007, 0.063±0.002, 0.034±0.002 and 0.092±0.002, respectively; whereas, methyl parathion was not detected in any of the analyzed samples. Quantitative structure activity relationship (QSAR) models were suggested to predict the residues of unknown pesticides in the goat milk using their known physicochemical characteristics including molecular weight (MW), melting point (MP), and log octanol to water partition coefficient (Ko/w) in relation to the characteristics such as pH, % fat, specific gravity and refractive index of goat milk. The analysis revealed good correlation coefficient (R2 = 0.985) for goat QSAR model. The coefficients for Ko/w and refractive index for the studied pesticides were higher in goat milk. This suggests that these are better determinants for pesticide residue prediction in the milk of these animals. Based upon the determined pesticide residues and their provisional tolerable daily intakes, risk analysis was also conducted which showed that daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study are 2.68, 5.19 and 2.71 times higher, respectively in the goat milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

  9. Quantitative Structure Activity Relationship and Risk Analysis of Some Pesticides in the Goat milk

    Directory of Open Access Journals (Sweden)

    Faqir Muhammad

    2013-01-01

    Full Text Available The detection and quantification of different pesticides in the goat milk samples collected from different localities of Faisalabad, Pakistan was performed by HPLC using solid phase microextraction. The analysis showed that about 50% milk samples were contaminated with pesticides. The mean+/-SEM levels (ppm of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.34+/-0.007, 0.063+/-0.002, 0.034+/-0.002 and 0.092+/-0.002, respectively; whereas, methyl parathion was not detected in any of the analyzed samples. Quantitative structure activity relationship (QSAR models were suggested to predict the residues of unknown pesticides in the goat milk using their known physicochemical characteristics including molecular weight (MW, melting point (MP, and log octanol to water partition coefficient (Ko/w in relation to the characteristics such as pH, % fat, specific gravity and refractive index of goat milk. The analysis revealed good correlation coefficient (R2 = 0.985 for goat QSAR model. The coefficients for Ko/w and refractive index for the studied pesticides were higher in goat milk. This suggests that these are better determinants for pesticide residue prediction in the milk of these animals. Based upon the determined pesticide residues and their provisional tolerable daily intakes, risk analysis was also conducted which showed that daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study are 2.68, 5.19 and 2.71 times higher, respectively in the goat milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

  10. Structure Activity Relationships of α-L-LNA Modified Phosphorothioate Gapmer Antisense Oligonucleotides in Animals

    Directory of Open Access Journals (Sweden)

    Punit P Seth

    2012-01-01

    Full Text Available We report the structure activity relationships of short 14-mer phosphorothioate gapmer antisense oligonucleotides (ASOs modified with α-L-locked nucleic acid (LNA and related modifications targeting phosphatase and tensin homologue (PTEN messenger RNA in mice. α-L-LNA represents the α-anomer of enantio-LNA and modified oligonucleotides show LNA like binding affinity for complementary RNA. In contrast to sequence matched LNA gapmer ASOs which showed elevations in plasma alanine aminotransferase (ALT levels indicative of hepatotoxicity, gapmer ASOs modified with α-L-LNA and related analogs in the flanks showed potent downregulation of PTEN messenger RNA in liver tissue without producing elevations in plasma ALT levels. However, the α-L-LNA ASO showed a moderate dose-dependent increase in liver and spleen weights suggesting a higher propensity for immune stimulation. Interestingly, replacing α-L-LNA nucleotides in the 3′- and 5′-flanks with R-5′-Me-α-L-LNA but not R-6′-Me- or 3′-Me-α-L-LNA nucleotides, reversed the drug induced increase in organ weights. Examination of structural models of dinucleotide units suggested that the 5′-Me group increases steric bulk in close proximity to the phosphorothioate backbone or produces subtle changes in the backbone conformation which could interfere with recognition of the ASO by putative immune receptors. Our data suggests that introducing steric bulk at the 5′-position of the sugar-phosphate backbone could be a general strategy to mitigate the immunostimulatory profile of oligonucleotide drugs. In a clinical setting, proinflammatory effects manifest themselves as injection site reactions and flu-like symptoms. Thus, a mitigation of these effects could increase patient comfort and compliance when treated with ASOs.

  11. An automated pulse labelling method for structure-activity relationship studies with antibacterial oxazolidinones.

    Science.gov (United States)

    Eustice, D C; Brittelli, D R; Feldman, P A; Brown, L J; Borkowski, J J; Slee, A M

    1990-01-01

    The 3-aryl-2-oxooxazolidinones are a new class of synthetic antibacterial agents that potently inhibit protein synthesis. An automated pulse labelling method with [3H]-lysine was developed with Bacillus subtilis to obtain additional quantitative activity data for structure-activity relationship studies with the oxazolidinones. Inhibition constants were calculated after a Logit fit of the data into the formula: % of control = 100/(1 + e[-B(X - A)]), where B is the slope of the model, X is the natural log of the inhibitor concentration and A is the natural log of the inhibitor concentration required to inhibit protein synthesis by 50% (ln IC50). When substituents at the 5-methyl position of the heterocyclic ring (B-substituent) were NHCOCH3, OH or Cl, the correlation coefficient was 0.87 between the MIC and IC50 values (for all compounds with MICs less than or equal to 16 micrograms/ml). The D-isomers of DuP 721 (A-substituent = CH3CO) and DuP 105 (A-substituent = CH3SO) gave MICs of 128 micrograms/ml and IC50s of greater than or equal to 50 micrograms/ml for protein synthesis, showing that only the L-isomers were active. By MIC testing, oxazolidinones with the B-substituent of NHCOCH3 and the A-substituent of CH3CO, NO2, CH3S, CH3SO2 or (CH3)2CH had comparable antibacterial potency; however, pulse labelling analysis showed that compounds with an A-substituent of CH3CO or NO2 were more potent inhibitors of protein synthesis.

  12. QUANTITAVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR OF ANTIMALARIAL 1,10-PHENANTHROLINE DERIVATIVES COMPOUNDS

    Directory of Open Access Journals (Sweden)

    Ruslin Hadanu

    2010-06-01

    Full Text Available Quantitative Electronic Structure-Activity Relationship (QSAR analysis of a series of 1,10-phenanthroline derivatives as antiplasmodial compounds have been conducted using atomic net charges (q, dipole moment (μ ELUMO, EHOMO, polarizability (α and log P as the descriptors. The descriptors were obtained from computational chemistry method using semi-empirical PM3. Antiplasmodial activities were taken as the activity of the drugs  against  chloroquine-resistant Plasmodium falciparum FCR3 strain and are presented as the value of ln (1/IC50 where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best model of QSAR model was determine by multiple linear regression method and giving equation of QSAR: ln 1/IC50  =  3.732 + (5.098 qC5 + (7.051 qC7 + (36.696 qC9 + (41.467 qC11 -(135.497 qC12 + (0.332 μ -                    (0.170 α + (0.757 log P. The equation was significant on the 95% level with statistical parameters: n=16; r=0.987; r2= 0.975; SE=0.317;  Fcalc/Ftable = 15.337 and gave the PRESS=0.707. Its means that there were only a relatively few deviations between the experimental and theoretical data of antimalarial activity.   Keywords: QSAR, antimalarial, semi-empirical method, 1,10-phenanthroline.

  13. Validation of Quantitative Structure-Activity Relationship (QSAR Model for Photosensitizer Activity Prediction

    Directory of Open Access Journals (Sweden)

    Sharifuddin M. Zain

    2011-11-01

    Full Text Available Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA method. Based on the method, r2 value, r2 (CV value and r2 prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC50 values ranging from 0.39 µM to 7.04 µM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r2 prediction for external test set of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.

  14. Molecular Docking, Molecular Dynamics, and Structure-Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists.

    Science.gov (United States)

    Noha, Stefan M; Schmidhammer, Helmut; Spetea, Mariana

    2017-06-21

    Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure-activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3-7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design.

  15. Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein

    DEFF Research Database (Denmark)

    Zhang, Hang; Xiong, Xiao-feng; Boesgaard, Michael W

    2017-01-01

    that specifically inhibit signaling mediated by the Gq subfamily. In this study we exploit a newly developed synthetic strategy for this compound class in the design, synthesis, and pharmacological evaluation of eight new analogues of YM-254890. These structure-activity relationship studies led to the discovery...

  16. Quantitative structure-activity relationship modeling of the toxicity of organothiophosphate pesticides to Daphnia magna and Cyprinus carpio

    NARCIS (Netherlands)

    Zvinavashe, E.; Du, T.; Griff, T.; Berg, van den J.H.J.; Soffers, A.E.M.F.; Vervoort, J.J.M.; Murk, A.J.; Rietjens, I.

    2009-01-01

    Within the REACH regulatory framework in the EU, quantitative structure-activity relationships (QSAR) models are expected to help reduce the number of animals used for experimental testing. The objective of this study was to develop QSAR models to describe the acute toxicity of organothiophosphate

  17. Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships (MCBIOS)

    Science.gov (United States)

    Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships Jie Liu1,2, Richard Judson1, Matthew T. Martin1, Huixiao Hong3, Imran Shah1 1National Center for Computational Toxicology (NCCT), US EPA, RTP, NC...

  18. Discovery and Structure-Activity Relationship of a Bioactive Fragment of ELABELA that Modulates Vascular and Cardiac Functions

    NARCIS (Netherlands)

    Murza, Alexandre; Sainsily, Xavier; Coquerel, David; Côté, Jérôme; Marx, Patricia; Besserer-Offroy, Élie; Longpré, Jean-Michel; Lainé, Jean; Reversade, Bruno; Salvail, Dany; Leduc, Richard; Dumaine, Robert; Lesur, Olivier; Auger-Messier, Mannix; Sarret, Philippe; Marsault, Éric

    2016-01-01

    ELABELA (ELA) was recently discovered as a novel endogenous ligand of the apelin receptor (APJ), a G protein-coupled receptor. ELA signaling was demonstrated to be crucial for normal heart and vasculature development during embryogenesis. We delineate here ELA's structure- activity relationships and

  19. Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1

    Directory of Open Access Journals (Sweden)

    Li-Wei Zou

    2017-06-01

    Full Text Available Human carboxylesterase 1 (hCE1, one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs were assayed using D-Luciferin methyl ester (DME and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB as specific optical substrate for hCE1, and hCE2, respectively. Following screening of a series of natural triterpenoids, oleanolic acid (OA, and ursolic acid (UA were found with strong inhibitory effects on hCE1 and relative high selectivity over hCE2. In order to get the highly selective and potent inhibitors of hCE1, a series of OA and UA derivatives were synthesized from OA and UA by chemical modifications including oxidation, reduction, esterification, and amidation. The inhibitory effects of these derivatives on hCEs were assayed and the structure-activity relationships of tested triterpenoids as hCE1 inhibitors were carefully investigated. The results demonstrated that the carbonyl group at the C-28 site is essential for hCE1 inhibition, the modifications of OA or UA at this site including esters, amides and alcohols are unbeneficial for hCE1 inhibition. In contrast, the structural modifications on OA and UA at other sites, such as converting the C-3 hydroxy group to 3-O-β-carboxypropionyl (compounds 20 and 22, led to a dramatically increase of the inhibitory effects against hCE1 and very high selectivity over hCE2. 3D-QSAR analysis of all tested triterpenoids including OA and UA derivatives provide new insights into the fine relationships linking between the inhibitory effects on hCE1 and the steric-electrostatic properties of triterpenoids. Furthermore, both inhibition kinetic analyses and docking

  20. Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28.

    Science.gov (United States)

    Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

    2005-10-06

    US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

  1. In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

    International Nuclear Information System (INIS)

    Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaelle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Francoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Veronique; Dufrasne, Francois; Van Antwerpen, Pierre; Poumay, Yves

    2011-01-01

    The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.

  2. Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus.

    Science.gov (United States)

    Li, Sumei; Jia, Xiuhua; Shen, Xintian; Wei, Zhuwen; Jiang, Zhiyan; Liao, Yixian; Guo, Yiming; Zheng, Xiaojun; Zhong, Guohua; Song, Gaopeng

    2017-08-15

    Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC 50 values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Structure-activity relationships for serotonin transporter and dopamine receptor selectivity.

    Science.gov (United States)

    Agatonovic-Kustrin, Snezana; Davies, Paul; Turner, Joseph V

    2009-05-01

    Antipsychotic medications have a diverse pharmacology with affinity for serotonergic, dopaminergic, adrenergic, histaminergic and cholinergic receptors. Their clinical use now also includes the treatment of mood disorders, thought to be mediated by serotonergic receptor activity. The aim of our study was to characterise the molecular properties of antipsychotic agents, and to develop a model that would indicate molecular specificity for the dopamine (D(2)) receptor and the serotonin (5-HT) transporter. Back-propagation artificial neural networks (ANNs) were trained on a dataset of 47 ligands categorically assigned antidepressant or antipsychotic utility. The structure of each compound was encoded with 63 calculated molecular descriptors. ANN parameters including hidden neurons and input descriptors were optimised based on sensitivity analyses, with optimum models containing between four and 14 descriptors. Predicted binding preferences were in excellent agreement with clinical antipsychotic or antidepressant utility. Validated models were further tested by use of an external prediction set of five drugs with unknown mechanism of action. The SAR models developed revealed the importance of simple molecular characteristics for differential binding to the D(2) receptor and the 5-HT transporter. These included molecular size and shape, solubility parameters, hydrogen donating potential, electrostatic parameters, stereochemistry and presence of nitrogen. The developed models and techniques employed are expected to be useful in the rational design of future therapeutic agents.

  4. Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.

    Directory of Open Access Journals (Sweden)

    Megan Leander

    Full Text Available Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS, a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (RhpMS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3-6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3-6 lock

  5. Obscure phenomena in statistical analysis of quantitative structure-activity relationships. Part 1: Multicollinearity of physicochemical descriptors.

    Science.gov (United States)

    Mager, P P; Rothe, H

    1990-10-01

    Multicollinearity of physicochemical descriptors leads to serious consequences in quantitative structure-activity relationship (QSAR) analysis, such as incorrect estimators and test statistics of regression coefficients of the ordinary least-squares (OLS) model applied usually to QSARs. Beside the diagnosis of the known simple collinearity, principal component regression analysis (PCRA) also allows the diagnosis of various types of multicollinearity. Only if the absolute values of PCRA estimators are order statistics that decrease monotonically, the effects of multicollinearity can be circumvented. Otherwise, obscure phenomena may be observed, such as good data recognition but low predictive model power of a QSAR model.

  6. Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.

    Science.gov (United States)

    Sun, Wenlong; Zhuang, Chunlin; Li, Xia; Zhang, Bowei; Lu, Xinhua; Zheng, Zhihui; Dong, Yuesheng

    2017-08-01

    Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

    Science.gov (United States)

    Li, Minyong; Xia, Lin

    2007-11-01

    In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

  8. Predicting allergic contact dermatitis: a hierarchical structure activity relationship (SAR) approach to chemical classification using topological and quantum chemical descriptors

    Science.gov (United States)

    Basak, Subhash C.; Mills, Denise; Hawkins, Douglas M.

    2008-06-01

    A hierarchical classification study was carried out based on a set of 70 chemicals—35 which produce allergic contact dermatitis (ACD) and 35 which do not. This approach was implemented using a regular ridge regression computer code, followed by conversion of regression output to binary data values. The hierarchical descriptor classes used in the modeling include topostructural (TS), topochemical (TC), and quantum chemical (QC), all of which are based solely on chemical structure. The concordance, sensitivity, and specificity are reported. The model based on the TC descriptors was found to be the best, while the TS model was extremely poor.

  9. TRANSFORMATION OF DEVELOPMENTAL NEUROTOXICITY DATA INTO STRUCTURE-SEARCHABLE TOXML DATABASE IN SUPPORT OF STRUCTURE-ACTIVITY RELATIONSHIP (SAR) WORKFLOW.

    Science.gov (United States)

    Early hazard identification of new chemicals is often difficult due to lack of data on the novel material for toxicity endpoints, including neurotoxicity. At present, there are no structure searchable neurotoxicity databases. A working group was formed to construct a database to...

  10. Use of a (Quantitative) Structure-Activity Relationship [(Q)SAR] model to predict the toxicity of naphthenic acids

    DEFF Research Database (Denmark)

    Frank, Richard; Sanderson, Hans; Kavanagh, Richard

    2010-01-01

    Naphthenic acids (NAs) are a complex mixture of carboxylic acids that are natural constituents of oil sand found in north-eastern Alberta, Canada.  NAs are released and concentrated in the alkaline water used in the extraction of bitumen from oil sand sediment.  NAs have been identified...... as the principal toxic components of oil sands process-affected water (OSPW), and microbial degradation of lower molecular weight (MW) NAs decreases the toxicity of NA mixtures in OSPW.  Analysis by proton nuclear magnetic resonance spectroscopy indicated that larger, more cyclic NAs contain greater carboxylic...

  11. Fragment-based quantitative structure-activity relationship (FB-QSAR) for fragment-based drug design.

    Science.gov (United States)

    Du, Qi-Shi; Huang, Ri-Bo; Wei, Yu-Tuo; Pang, Zong-Wen; Du, Li-Qin; Chou, Kuo-Chen

    2009-01-30

    In cooperation with the fragment-based design a new drug design method, the so-called "fragment-based quantitative structure-activity relationship" (FB-QSAR) is proposed. The essence of the new method is that the molecular framework in a family of drug candidates are divided into several fragments according to their substitutes being investigated. The bioactivities of molecules are correlated with the physicochemical properties of the molecular fragments through two sets of coefficients in the linear free energy equations. One coefficient set is for the physicochemical properties and the other for the weight factors of the molecular fragments. Meanwhile, an iterative double least square (IDLS) technique is developed to solve the two sets of coefficients in a training data set alternately and iteratively. The IDLS technique is a feedback procedure with machine learning ability. The standard Two-dimensional quantitative structure-activity relationship (2D-QSAR) is a special case, in the FB-QSAR, when the whole molecule is treated as one entity. The FB-QSAR approach can remarkably enhance the predictive power and provide more structural insights into rational drug design. As an example, the FB-QSAR is applied to build a predictive model of neuraminidase inhibitors for drug development against H5N1 influenza virus. (c) 2008 Wiley Periodicals, Inc.

  12. Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship.

    Science.gov (United States)

    Hou, Jin-Jun; Shen, Yao; Yang, Zhou; Fang, Lin; Cai, Lu-Ying; Yao, Shuai; Long, Hua-Li; Wu, Wan-Ying; Guo, De-An

    2017-10-01

    Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC 50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  13. Molecular Descriptors Family on Structure Activity Relationships 6. Octanol-Water Partition Coefficient of Polychlorinated Biphenyls

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2006-01-01

    Full Text Available Octanol-water partition coefficient of two hundred and six polychlorinated biphenyls was model by the use of an original method based on complex information obtained from compounds structure. The regression analysis shows that best results are obtained in four-varied model (r2 = 0.9168. The prediction ability of the model was studied through leave-one-out analysis (r2cv(loo = 0.9093 and in training and test sets analysis. Modeling the octanol-water partition coefficient of polychlorinated biphenyls by integration of complex structural information provide a stable and performing four-varied model, allowing us to make remarks about relationship between structure of polychlorinated biphenyls and associated octanol-water partition coefficients.

  14. Synthesis and structure-activity relationship exploration of some potent anti-cancer phenyl amidrazone derivatives.

    Science.gov (United States)

    Habashneh, Almeqdad Y; El-Abadelah, Mustafa M; Bardaweel, Sanaa K; Taha, Mutasem O

    2017-12-04

    Amidrazones have been reported to have significant anti-tumor properties against several cancer cell lines. The current project aims to profile the structure-anticancer activity relationship of phenyl-amidrazons. Fifteen phenyl-amidrazone-piperazine derivatives were prepared and tested against four cancer cell lines (leukemia, prostate, breast and colon cancers). Six compounds illustrated low micromolar anticancer IC50 values, while the remaining compounds were either inactive or of moderate potencies. All compounds were virtually nontoxic against normal fibroblast cells. Docking into the oncogenic kinase bcr/abl illustrated the critical importance of (i) p-halogen substituent on the ligand's phenyl ring and (ii) the presence of positive ionizable moiety at the ligand's piperazine fragment for anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Nε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling.

    Science.gov (United States)

    Wodtke, Robert; Hauser, Christoph; Ruiz-Gómez, Gloria; Jäckel, Elisabeth; Bauer, David; Lohse, Martin; Wong, Alan; Pufe, Johanna; Ludwig, Friedrich-Alexander; Fischer, Steffen; Hauser, Sandra; Greif, Dieter; Pisabarro, M Teresa; Pietzsch, Jens; Pietsch, Markus; Löser, Reik

    2018-05-24

    Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N ε -acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M -1 s -1 , which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

  16. Structure-activity relationships of lanostane-type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors.

    Science.gov (United States)

    Fatmawati, Sri; Kondo, Ryuichiro; Shimizu, Kuniyoshi

    2013-11-01

    A series of lanostane-type triterpenoids, identified as ganoderma alcohols and ganoderma acids, were isolated from the fruiting body of Ganoderma lingzhi. Some of these compounds were confirmed as active inhibitors of the in vitro human recombinant aldose reductase. This paper aims to explain the structural requirement for α-glucosidase inhibition. Our structure-activity studies of ganoderma alcohols showed that the OH substituent at C-3 and the double-bond moiety at C-24 and C-25 are necessary to increase α-glucosidase inhibitory activity. The structure-activity relationships of ganoderma acids revealed that the OH substituent at C-11 is an important feature and that the carboxylic group in the side chain is essential for the recognition of α-glucosidase inhibitory activity. Moreover, the double-bond moiety at C-20 and C-22 in the side chain and the OH substituent at C-3 of ganoderma acids improve α-glucosidase inhibitory activity. These results provide an approach with which to consider the structural requirements of lanostane-type triterpenoids from G. lingzhi. An understanding of these requirements is considered necessary in order to improve a new type of α-glucosidase inhibitor. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Structure-activity relationships and prediction of the phototoxicity and phototoxic potential of new drugs.

    Science.gov (United States)

    Barratt, Martin D

    2004-11-01

    Relationships between the structure and properties of chemicals can be programmed into knowledge-based systems such as DEREK for Windows (DEREK is an acronym for "Deductive Estimation of Risk from Existing Knowledge"). The DEREK for Windows computer system contains a subset of over 60 rules describing chemical substructures (toxophores) responsible for skin sensitisation. As part of the European Phototox Project, the rule base was supplemented by a number of rules for the prospective identification of photoallergens, either by extension of the scope of existing rules or by the generation of new rules where a sound mechanistic rationale for the biological activity could be established. The scope of the rules for photoallergenicity was then further refined by assessment against a list of chemicals identified as photosensitisers by the Centro de Farmacovigilancia de la Comunidad Valenciana, Valencia, Spain. This paper contains an analysis of the mechanistic bases of activity for eight important groups of photoallergens and phototoxins, together with rules for the prospective identification of the photobiological activity of new or untested chemicals belonging to those classes. The mechanism of action of one additional chemical, nitrofurantoin, is well established; however, it was deemed inappropriate to write a rule on the basis of a single chemical structure.

  18. An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

    Science.gov (United States)

    Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

    2017-04-01

    Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

  19. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study.

    Science.gov (United States)

    Proença, Carina; Freitas, Marisa; Ribeiro, Daniela; Oliveira, Eduardo F T; Sousa, Joana L C; Tomé, Sara M; Ramos, Maria J; Silva, Artur M S; Fernandes, Pedro A; Fernandes, Eduarda

    2017-12-01

    α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme's activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure-activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC 50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.

  20. Structure-activity relationship of 9-methylstreptimidone, a compound that induces apoptosis selectively in adult T-cell leukemia cells.

    Science.gov (United States)

    Takeiri, Masatoshi; Ota, Eisuke; Nishiyama, Shigeru; Kiyota, Hiromasa; Umezawa, Kazuo

    2012-01-01

    We previously reported that 9-methylstreptimidone, a piperidine compound isolated from a culture filtrate of Streptomyces, induces apoptosis selectively in adult T-cell leukemia cells. It was screened for a compound that inhibits LPS-induced NF-kappaB and NO production in mouse macrophages. However, 9-methystreptimidone is poorly obtained from the producing microorganism and difficult to synthesize. Therefore, in the present research, we studied the structure-activity relationship to look for new selective inhibitors. We found that the structure of the unsaturated hydrophobic portion of 9-methylstreptimidone was essential for the inhibition of LPS-induced NO production. Among the 9-methylstreptimidone-related compounds tested, (+/-)-4,alpha-diepi-streptovitacin A inhibited NO production in macrophage-like cells as potently as 9-methylstreptimidone and without cellular toxicity. Moreover, this compound selectively induced apoptosis in adult T-cell leukemia MT-1 cells.

  1. Non-linear quantitative structure-activity relationship for adenine derivatives as competitive inhibitors of adenosine deaminase

    International Nuclear Information System (INIS)

    Sadat Hayatshahi, Sayyed Hamed; Abdolmaleki, Parviz; Safarian, Shahrokh; Khajeh, Khosro

    2005-01-01

    Logistic regression and artificial neural networks have been developed as two non-linear models to establish quantitative structure-activity relationships between structural descriptors and biochemical activity of adenosine based competitive inhibitors, toward adenosine deaminase. The training set included 24 compounds with known k i values. The models were trained to solve two-class problems. Unlike the previous work in which multiple linear regression was used, the highest of positive charge on the molecules was recognized to be in close relation with their inhibition activity, while the electric charge on atom N1 of adenosine was found to be a poor descriptor. Consequently, the previously developed equation was improved and the newly formed one could predict the class of 91.66% of compounds correctly. Also optimized 2-3-1 and 3-4-1 neural networks could increase this rate to 95.83%

  2. Structure-activity relationships for novel drug precursor N-substituted-6-acylbenzothiazolon derivatives: A theoretical approach

    Science.gov (United States)

    Sıdır, Yadigar Gülseven; Sıdır, İsa

    2013-08-01

    In this study, the twelve new modeled N-substituted-6-acylbenzothiazolon derivatives having analgesic analog structure have been investigated by quantum chemical methods using a lot of electronic parameters and structure-activity properties; such as molecular polarizability (α), dipole moment (μ), EHOMO, ELUMO, q-, qH+, molecular volume (Vm), ionization potential (IP), electron affinity (EA), electronegativity (χ), molecular hardness (η), molecular softness (S), electrophilic index (ω), heat of formation (HOF), molar refractivity (MR), octanol-water partition coefficient (log P), thermochemical properties (entropy (S), capacity of heat (Cv)); as to investigate activity relationships with molecular structure. The correlations of log P with Vm, MR, ω, EA, EHOMO - ELUMO (ΔE), HOF in aqueous phase, χ, μ, S, η parameters, respectively are obtained, while the linear relation of log P with IP, Cv, HOF in gas phase are not observed. The log P parameter is obtained to be depending on different properties of compounds due to their complexity.

  3. Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.

    Science.gov (United States)

    Menezes, Carla M S; Rivera, Gildardo; Alves, Marina A; do Amaral, Daniel N; Thibaut, Jean Pierre B; Noël, François; Barreiro, Eliezer J; Lima, Lídia M

    2012-06-01

    The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. © 2012 John Wiley & Sons A/S.

  4. Structure-activity relationship of pentacylic triterpene esters from Uncaria rhynchophylla as inhibitors of phospholipase Cgamma1.

    Science.gov (United States)

    Lee, Ji Suk; Yoo, Hunseung; Suh, Young Ger; Jung, Jae Kyung; Kim, Jinwoong

    2008-10-01

    A systematic structure-activity relationship of 3beta-hydroxy-27- P- E-coumaroyloxyurs-12-en-28-oic acid ( 7), a triterpene ester isolated from UNCARIA RHYNCHOPHYLLA as a phospholipase Cgamma1 inhibitor, was undertaken with a view toward elucidating its chemical mode of action on PLCgamma1. Related derivatives and analogues of 7 were synthesized and their inhibitory activities against PLCgamma1 were evaluated IN VITRO. The results indicate that 3-OH and 27-esterification may be essential, and that 28-COOH and the 2' double bond appear to be important for activity. Furthermore, the compound possessing a P-coumaroyloxy at position 27 rather than at the 3 and 28 positions shows the greatest inhibitory activity against PLCgamma1. Therefore, this inhibitor will be providing a chemical lead for the further development of cancer chemopreventive or cancer chemotherapeutic agents that have lower toxicity against normal tissues.

  5. Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein.

    Science.gov (United States)

    Zhang, Hang; Xiong, Xiao-Feng; Boesgaard, Michael W; Underwood, Christina R; Bräuner-Osborne, Hans; Strømgaard, Kristian

    2017-06-07

    Extracellular signals perceived by G protein-coupled receptors are transmitted via G proteins, and subsequent intracellular signaling cascades result in a plethora of physiological responses. The natural product cyclic depsipeptides YM-254890 and FR900359 are the only known compounds that specifically inhibit signaling mediated by the G q subfamily. In this study we exploit a newly developed synthetic strategy for this compound class in the design, synthesis, and pharmacological evaluation of eight new analogues of YM-254890. These structure-activity relationship studies led to the discovery of three new analogues, YM-13, YM-14, and YM-18, which displayed potent and selective G q inhibitory activity. This provides pertinent information for the understanding of the G q inhibitory mechanism by this class of compounds and importantly provides a pathway for the development of labeled YM-254890 analogues. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Quantitative structure-activation barrier relationship modeling for Diels-Alder ligations utilizing quantum chemical structural descriptors.

    Science.gov (United States)

    Nandi, Sisir; Monesi, Alessandro; Drgan, Viktor; Merzel, Franci; Novič, Marjana

    2013-10-30

    In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software. Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers. A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation.

  7. Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH analogs: iron chelation, anti-oxidant and cytotoxic properties.

    Directory of Open Access Journals (Sweden)

    Eliška Potůčková

    Full Text Available Salicylaldehyde isonicotinoyl hydrazone (SIH is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability. Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O, which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

  8. Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

    Science.gov (United States)

    Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

    2016-01-01

    We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

  9. Synthesis and Structure-Activity Relationships of a Series of Aporphine Derivatives with Antiarrhythmic Activities and Acute Toxicity

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2016-11-01

    Full Text Available Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF, induced by CHCl3, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl2. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d, three bromo-substituted products of crebanine (2a, 2b, 2c, N-methylcrebanine (2d, and dehydrostephanine (4a displayed antiarrhythmic effects in the CHCl3-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl3 (p < 0.05, increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl2 (p < 0.01, and the number of rats that maintained sinus rhythm for more than 20 min (p < 0.01. Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD50 = 59.62 mg/kg, mice, simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.

  10. Synthesis and Structure-Activity Relationship of Griseofulvin Analogues as Inhibitors of Centrosomal Clustering in Cancer Cells

    DEFF Research Database (Denmark)

    Rønnest, Mads Holger; Rebacz, Blanka; Markworth, Lene

    2009-01-01

    Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34 griseoful......Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34...

  11. Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells.

    Science.gov (United States)

    Jiang, Wen-Jun; Daikonya, Akihiro; Ohkawara, Mitsuyoshi; Nemoto, Takashi; Noritake, Ryusuke; Takamiya, Tomoko; Kitanaka, Susumu; Iijima, Hiroshi

    2017-01-15

    We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R 3' =R 5' ). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q 2 value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Modeling the Dispersibility of Single Walled Carbon Nanotubes in Organic Solvents by Quantitative Structure-Activity Relationship Approach

    Science.gov (United States)

    Yilmaz, Hayriye; Rasulev, Bakhtiyor; Leszczynski, Jerzy

    2015-01-01

    The knowledge of physico-chemical properties of carbon nanotubes, including behavior in organic solvents is very important for design, manufacturing and utilizing of their counterparts with improved properties. In the present study a quantitative structure-activity/property relationship (QSAR/QSPR) approach was applied to predict the dispersibility of single walled carbon nanotubes (SWNTs) in various organic solvents. A number of additive descriptors and quantum-chemical descriptors were calculated and utilized to build QSAR models. The best predictability is shown by a 4-variable model. The model showed statistically good results (R2training = 0.797, Q2 = 0.665, R2test = 0.807), with high internal and external correlation coefficients. Presence of the X0Av descriptor and its negative term suggest that small size solvents have better SWCNTs solubility. Mass weighted descriptor ATS6m also indicates that heavier solvents (and small in size) most probably are better solvents for SWCNTs. The presence of the Dipole Z descriptor indicates that higher polarizability of the solvent molecule increases the solubility. The developed model and contributed descriptors can help to understand the mechanism of the dispersion process and predictorganic solvents that improve the dispersibility of SWNTs. PMID:28347035

  13. A Review of Recent Advances towards the Development of (Quantitative Structure-Activity Relationships for Metallic Nanomaterials

    Directory of Open Access Journals (Sweden)

    Guangchao Chen

    2017-08-01

    Full Text Available Gathering required information in a fast and inexpensive way is essential for assessing the risks of engineered nanomaterials (ENMs. The extension of conventional (quantitative structure-activity relationships ((QSARs approach to nanotoxicology, i.e., nano-(QSARs, is a possible solution. The preliminary attempts of correlating ENMs’ characteristics to the biological effects elicited by ENMs highlighted the potential applicability of (QSARs in the nanotoxicity field. This review discusses the current knowledge on the development of nano-(QSARs for metallic ENMs, on the aspects of data sources, reported nano-(QSARs, and mechanistic interpretation. An outlook is given on the further development of this frontier. As concluded, the used experimental data mainly concern the uptake of ENMs by different cell lines and the toxicity of ENMs to cells lines and Escherichia coli. The widely applied techniques of deriving models are linear and non-linear regressions, support vector machine, artificial neural network, k-nearest neighbors, etc. Concluded from the descriptors, surface properties of ENMs are seen as vital for the cellular uptake of ENMs; the capability of releasing ions and surface redox properties of ENMs are of importance for evaluating nanotoxicity. This review aims to present key advances in relevant nano-modeling studies and stimulate future research efforts in this quickly developing field of research.

  14. Modeling the Dispersibility of Single Walled Carbon Nanotubes in Organic Solvents by Quantitative Structure-Activity Relationship Approach

    Directory of Open Access Journals (Sweden)

    Hayriye Yilmaz

    2015-05-01

    Full Text Available The knowledge of physico-chemical properties of carbon nanotubes, including behavior in organic solvents is very important for design, manufacturing and utilizing of their counterparts with improved properties. In the present study a quantitative structure-activity/property relationship (QSAR/QSPR approach was applied to predict the dispersibility of single walled carbon nanotubes (SWNTs in various organic solvents. A number of additive descriptors and quantum-chemical descriptors were calculated and utilized to build QSAR models. The best predictability is shown by a 4-variable model. The model showed statistically good results (R2training = 0.797, Q2 = 0.665, R2test = 0.807, with high internal and external correlation coefficients. Presence of the X0Av descriptor and its negative term suggest that small size solvents have better SWCNTs solubility. Mass weighted descriptor ATS6m also indicates that heavier solvents (and small in size most probably are better solvents for SWCNTs. The presence of the Dipole Z descriptor indicates that higher polarizability of the solvent molecule increases the solubility. The developed model and contributed descriptors can help to understand the mechanism of the dispersion process and predictorganic solvents that improve the dispersibility of SWNTs.

  15. Isolation of Insecticidal Constituent from Ruta graveolens and Structure-Activity Relationship Studies against Stored-Food Pests (Coleoptera).

    Science.gov (United States)

    Jeon, Ju-Hyun; Lee, Sang-Guei; Lee, Hoi-Seon

    2015-08-01

    Isolates from essential oil extracted from the flowers and leaves of Ruta graveolens and commercial phenolic analogs were evaluated using fumigant and contact toxicity bioassays against adults of the stored-food pests Sitophilus zeamais, Sitophilus oryzae, and Lasioderma serricorne. The insecticidal activity of these compounds was then compared with that of the synthetic insecticide dichlorvos. To investigate the structure-activity relationships, the activity of 2-isopropyl-5-methylphenol and its analogs was examined against these stored-food pests. Based on the 50% lethal dose, the most toxic compound against S. zeamais was 3-isopropylephenol, followed by 2-isopropylphenol, 4-isopropylphenol, 5-isopropyl-2-methylphenol, 2-isopropyl-5-methylphenol, 3-methylphenol, and 2-methylphenol. Similar results were observed with phenolic compounds against S. oryzae. However, when 2-isopropyl-5-methylphenol isolated from R. graveolens oil and its structurally related analogs were used against L. serricorne, little or no insecticidal activity was found regardless of bioassay. These results indicate that introducing and changing the positions of functional groups in the phenol skeleton have an important effect on insecticidal activity of these compounds against stored-food pests.

  16. Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

    Science.gov (United States)

    Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

    2011-04-14

    Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

  17. Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.

    Science.gov (United States)

    Bahl, Deepa; Athar, Fareeda; Soares, Milena Botelho Pereira; de Sá, Matheus Santos; Moreira, Diogo Rodrigo Magalhães; Srivastava, Rajendra Mohan; Leite, Ana Cristina Lima; Azam, Amir

    2010-09-15

    A useful concept for the rational design of antiparasitic drug candidates is the complexation of bioactive ligands with transition metals. In view of this, an investigation was conducted into a new set of metal complexes as potential antiplasmodium and antiamoebic agents, in order to examine the importance of metallic atoms, as well as the kind of sphere of co-ordination, in these biological properties. Four functionalized furyl-thiosemicarbazones (NT1-4) treated with divalent metals (Cu, Co, Pt, and Pd) to form the mononuclear metallic complexes of formula [M(L)2Cl2] or [M(L)Cl2] were examined. The pharmacological characterization, including assays against Plasmodium falciparum and Entamoeba histolytica, cytotoxicity to mammalian cells, and interaction with pBR 322 plasmid DNA was performed. Structure-activity relationship data revealed that the metallic complexation plays an essential role in antiprotozoal activity, rather than the simple presence of the ligand or metal alone. Important steps towards identification of novel antiplasmodium (NT1Cu, IC50 of 4.6 microM) and antiamoebic (NT2Pd, IC50 of 0.6 microM) drug prototypes were achieved. Of particular relevance to this work, these prototypes were able to reduce the proliferation of these parasites at concentrations that are not cytotoxic to mammalian cells. Copyright (c) 2010. Published by Elsevier Ltd.

  18. Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti-inflammatory and Anticolitis Effects of Curcumin.

    Science.gov (United States)

    Yang, Haixia; Du, Zheyuan; Wang, Weicang; Song, Mingyue; Sanidad, Katherine; Sukamtoh, Elvira; Zheng, Jennifer; Tian, Li; Xiao, Hang; Liu, Zhenhua; Zhang, Guodong

    2017-06-07

    Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO 2 -, CH 3 -, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.

  19. Application of quantitative structure-activity relationship to the determination of binding constant based on fluorescence quenching

    Energy Technology Data Exchange (ETDEWEB)

    Wen Yingying [Department of Applied Chemistry, Yantai University, Yantai 264005 (China); Liu Huitao, E-mail: liuht-ytu@163.co [Department of Applied Chemistry, Yantai University, Yantai 264005 (China); Luan Feng; Gao Yuan [Department of Applied Chemistry, Yantai University, Yantai 264005 (China)

    2011-01-15

    Quantitative structure-activity relationship (QSAR) model was used to predict and explain binding constant (log K) determined by fluorescence quenching. This method allowed us to predict binding constants of a variety of compounds with human serum albumin (HSA) based on their structures alone. Stepwise multiple linear regression (MLR) and nonlinear radial basis function neural network (RBFNN) were performed to build the models. The statistical parameters provided by the MLR model (R{sup 2}=0.8521, RMS=0.2678) indicated satisfactory stability and predictive ability while the RBFNN predictive ability is somewhat superior (R{sup 2}=0.9245, RMS=0.1736). The proposed models were used to predict the binding constants of two bioactive components in traditional Chinese medicines (isoimperatorin and chrysophanol) whose experimental results were obtained in our laboratory and the predicted results were in good agreement with the experimental results. This QSAR approach can contribute to a better understanding of structural factors of the compounds responsible for drug-protein interactions, and can be useful in predicting the binding constants of other compounds. - Research Highlights: QSAR models for binding constants of some compounds to HSA were developed. The models provide a simple and straightforward way to predict binding constant. QSAR can give some insight into structural features related to binding behavior.

  20. A quantitative structure-activity relationship to predict efficacy of granular activated carbon adsorption to control emerging contaminants.

    Science.gov (United States)

    Kennicutt, A R; Morkowchuk, L; Krein, M; Breneman, C M; Kilduff, J E

    2016-08-01

    A quantitative structure-activity relationship was developed to predict the efficacy of carbon adsorption as a control technology for endocrine-disrupting compounds, pharmaceuticals, and components of personal care products, as a tool for water quality professionals to protect public health. Here, we expand previous work to investigate a broad spectrum of molecular descriptors including subdivided surface areas, adjacency and distance matrix descriptors, electrostatic partial charges, potential energy descriptors, conformation-dependent charge descriptors, and Transferable Atom Equivalent (TAE) descriptors that characterize the regional electronic properties of molecules. We compare the efficacy of linear (Partial Least Squares) and non-linear (Support Vector Machine) machine learning methods to describe a broad chemical space and produce a user-friendly model. We employ cross-validation, y-scrambling, and external validation for quality control. The recommended Support Vector Machine model trained on 95 compounds having 23 descriptors offered a good balance between good performance statistics, low error, and low probability of over-fitting while describing a wide range of chemical features. The cross-validated model using a log-uptake (qe) response calculated at an aqueous equilibrium concentration (Ce) of 1 μM described the training dataset with an r(2) of 0.932, had a cross-validated r(2) of 0.833, and an average residual of 0.14 log units.

  1. Designing quantitative structure activity relationships to predict specific toxic endpoints for polybrominated diphenyl ethers in mammalian cells.

    Science.gov (United States)

    Rawat, S; Bruce, E D

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants and have vast industrial application in products like plastics, building materials and textiles. They are found to be structurally similar to thyroid hormones that are responsible for regulating metabolism in the body. Structural similarity with the hormones poses a threat to human health because, once in the system, PBDEs have the potential to affect thyroid hormone transport and metabolism. This study was aimed at designing quantitative structure-activity relationship (QSAR) models for predicting toxic endpoints, namely cell viability and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated quantitatively using a general cytotoxicity bioassay using Janus Green dye and apoptosis was evaluated using a caspase assay. This study has thus modelled the overall cytotoxic influence of PBDEs at an early and a late endpoint by the Genetic Function Approximation method. This research was a twofold process including running in vitro bioassays to collect data on the toxic endpoints and modeling the evaluated endpoints using QSARs. Cell viability and apoptosis responses for Hep G2 cells exposed to PBDEs were successfully modelled with an r(2) of 0.97 and 0.94, respectively.

  2. Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae): structure/activity relationships.

    Science.gov (United States)

    Morais, Thiago R; da Costa-Silva, Thais A; Tempone, Andre G; Borborema, Samanta Etel T; Scotti, Marcus T; de Sousa, Raquel Maria F; Araujo, Ana Carolina C; de Oliveira, Alberto; de Morais, Sérgio Antônio L; Sartorelli, Patricia; Lago, João Henrique G

    2014-05-05

    Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.

  3. Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae: Structure/Activity Relationships

    Directory of Open Access Journals (Sweden)

    Thiago R. Morais

    2014-05-01

    Full Text Available Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae, and nine semi-synthetic derivatives were investigated against Leishmania (L. infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR data as well as electrospray ionization mass spectrometry (ESI-MS. Additionally, structure-activity relationships were performed using Decision Trees.

  4. Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

    Science.gov (United States)

    Kim, In-Hae; Park, Yong-Kyu; Nishiwaki, Hisashi; Hammock, Bruce D; Nishi, Kosuke

    2015-11-15

    Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as a secondary pharmacophore. A tert-butyl group (16) on the alpha carbon was found to yield most potent inhibition on the target enzyme. A 4-50-fold drop in inhibition was induced by other substituents such as aryls, substituted aryls, cycloalkyls, and alkyls. Then, the modification of the O-substituents on the phosphonate function revealed that diethyl groups (16 and 23) were preferable for inhibition to other longer alkyls or substituted alkyls. In amide compounds with the optimized diethylphosphonate moiety and an alkyl substitution such as adamantane (16), tetrahydronaphthalene (31), or adamantanemethane (36), highly potent inhibitions were gained. In addition, the resulting potent amide-phosphonate compounds had reasonable water solubility, suggesting that substituted phosphonates in amide inhibitors are effective for both inhibition potency on the human sEH and water solubility as a secondary pharmacophore. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR OF VINCADIFFORMINE ANALOGUES AS THE ANTIPLASMODIAL COMPOUNDS OF THE CHLOROQUINOSENSIBLE STRAIN

    Directory of Open Access Journals (Sweden)

    Iqmal Tahir

    2010-06-01

    Full Text Available Quantitative Structure-Activity Relationship (QSAR analysis of vincadifformine analogs as an antimalarial drug has been conducted using atomic net charges (q, moment dipole (, LUMO (Lowest Unoccupied Molecular Orbital and HOMO (Highest Occupied Molecular Orbital energies, molecular mass (m as well as surface area (A as the predictors to their activity. Data of predictors are obtained from computational chemistry method using semi-empirical molecular orbital AM1 calculation. Antimalarial activities were taken as the activity of the drugs against chloroquine-sensitive Plasmodium falciparum (Nigerian Cell strain and were presented as the value of ln(1/IC50 where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best QSAR model has been determined by multiple linier regression analysis giving QSAR equation: Log (1/IC50 = 9.602.qC1 -17.012.qC2 +6.084.qC3 -19.758.qC5 -6.517.qC6 +2.746.qC7 -6.795.qN +6.59.qC8 -0.190. -0.974.ELUMO +0.515.EHOMO -0.274. +0.029.A -1.673 (n = 16; r = 0.995; SD = 0.099; F = 2.682   Keywords: QSAR analysis, antimalaria, vincadifformine.

  6. Structural Characterization and Evaluation of the Antioxidant Activity of Phenolic Compounds from Astragalus taipaishanensis and Their Structure-Activity Relationship

    Science.gov (United States)

    Pu, Wenjun; Wang, Dongmei; Zhou, Dan

    2015-09-01

    Eight phenolic compounds were isolated using bio-guided isolation and purified from the roots of Astragalus taipaishanensis Y. C. Ho et S. B. Ho (A. taipaishanensis) for the first time. Their structures were elucidated by ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR as 7,2‧-dihydroxy-3‧,4‧-dimethoxy isoflavan (1), formononetin (2), isoliquiritigenin (3), quercetin (4), kaempferol (5), ononin (6), p-hydroxybenzoic acid (7) and vanillic acid (8). Six flavonoids (compounds 1-6) exhibited stronger antioxidant activities (determined by DPPH, ABTS, FRAP and lipid peroxidation inhibition assays) than those of BHA and TBHQ and also demonstrated noticeable protective effects (particularly quercetin and kaempferol) on Escherichia coli under oxidative stress. Additionally, the chemical constituents compared with those of Astragalus membranaceus and the structure-activity relationship of the isolated compounds were both analyzed. The results clearly demonstrated that A. taipaishanensis has the potential to be selected as an alternative medicinal and food plant that can be utilized in health food products, functional tea and pharmaceutical products.

  7. Quantitative structure-activity relationships of the antimalarial agent artemisinin and some of its derivatives - a DFT approach.

    Science.gov (United States)

    Rajkhowa, Sanchaita; Hussain, Iftikar; Hazarika, Kalyan K; Sarmah, Pubalee; Deka, Ramesh Chandra

    2013-09-01

    Artemisinin form the most important class of antimalarial agents currently available, and is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many derivatives of artemisinin were prepared. A comparative study on the chemical reactivity of artemisinin and some of its derivatives is performed using density functional theory (DFT) calculations. DFT based global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries are used to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the molecules. Multiple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on the DFT based descriptors against the chloroquine-resistant, mefloquine-sensitive Plasmodium falciparum W-2 clone.

  8. Structure-activity relationship and mechanism of action studies of manzamine analogues for the control of neuroinflammation and cerebral infections.

    Science.gov (United States)

    Peng, Jiangnan; Kudrimoti, Sucheta; Prasanna, Sivaprakasam; Odde, Srinivas; Doerksen, Robert J; Pennaka, Hari K; Choo, Yeun-Mun; Rao, Karumanchi V; Tekwani, Babu L; Madgula, Vamsi; Khan, Shabana I; Wang, Bin; Mayer, Alejandro M S; Jacob, Melissa R; Tu, Lan Chun; Gertsch, Jürg; Hamann, Mark T

    2010-01-14

    Structure-activity relationship studies were carried out by chemical modification of manzamine A (1), 8-hydroxymanzamine A (2), manzamine F (14), and ircinal isolated from the sponge Acanthostrongylophora. The derived analogues were evaluated for antimalarial, antimicrobial, and antineuroinflammatory activities. Several modified products exhibited potent and improved in vitro antineuroinflammatory, antimicrobial, and antimalarial activity. 1 showed improved activity against malaria compared to chloroquine in both multi- and single-dose in vivo experiments. The significant antimalarial potential was revealed by a 100% cure rate of malaria in mice with one administration of 100 mg/kg of 1. The potent antineuroinflammatory activity of the manzamines will provide great benefit for the prevention and treatment of cerebral infections (e.g., Cryptococcus and Plasmodium). In addition, 1 was shown to permeate across the blood-brain barrier (BBB) in an in vitro model using a MDR-MDCK monolayer. Docking studies support that 2 binds to the ATP-noncompetitive pocket of glycogen synthesis kinase-3beta (GSK-3beta), which is a putative target of manzamines. On the basis of the results presented here, it will be possible to initiate rational drug design efforts around this natural product scaffold for the treatment of several different diseases.

  9. Design, synthesis and structure-activity relationships studies on the D ring of the natural product triptolide.

    Science.gov (United States)

    Xu, Hongtao; Tang, Huanyu; Feng, Huijin; Li, Yuanchao

    2014-02-01

    Triptolide is a diterpene triepoxide natural product isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal herb. Triptolide has previously been shown to possess antitumor, anti-inflammatory, immunosuppressive, and antifertility activities. Earlier reports suggested that the five-membered unsaturated lactone ring (D ring) is essential for potent cytotoxicity, however, to the best of our knowledge, systematic structure-activity relationship studies have not yet been reported. Here, four types of D ring-modified triptolide analogues were designed, synthesized and evaluated against human ovarian (SKOV-3) and prostate (PC-3) carcinoma cell lines. The results suggest that the D ring is essential to potency, however it can be modified, for example to C18 hydrogen bond acceptor and/or donor furan ring analogues, without complete loss of cytotoxic activity. Interestingly, evaluation of the key series of C19 analogues showed that this site is exquisitely sensitive to polarity. Together, these results will guide further optimization of this natural product lead compound for the development of potent and potentially clinically useful triptolide analogues. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Quantitative structure-activity relationship analysis of substituted arylazo pyridone dyes in photocatalytic system: Experimental and theoretical study

    Energy Technology Data Exchange (ETDEWEB)

    Dostanić, J., E-mail: jasmina@nanosys.ihtm.bg.ac.rs [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Lončarević, D. [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Zlatar, M. [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade (Serbia); Vlahović, F. [University of Belgrade, Innovation center of the Faculty of Chemistry, 11000 Belgrade (Serbia); Jovanović, D.M. [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia)

    2016-10-05

    Highlights: • Electronic effects of para substituted arylazo pyridone dyes. • Linear relationship between Hammett σ{sub p} constants and dyes photoreactivity. • The photocatalytic reactions facilitated by el.-acceptors and retarded by el.-donors. • Fukui functions to analyze the reactivity on concurrent sites within a molecule. • Hydroxyl radicals sustain attack from two reaction sites, depending on a substituent type. - Abstract: A series of arylazo pyridone dyes was synthesized by changing the type of the substituent group in the diazo moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The structural and electronic properties of the investigated dyes was calculated at the M062X/6-31 + G(d,p) level of theory. The observed good linear correlations between atomic charges and Hammett σ{sub p} constants provided a basis to discuss the transmission of electronic substituent effects through a dye framework. The reactivity of synthesized dyes was tested through their decolorization efficiency in TiO{sub 2} photocatalytic system (Degussa P-25). Quantitative structure-activity relationship analysis revealed a strong correlation between reactivity of investigated dyes and Hammett substituent constants. The reaction was facilitated by electron-withdrawing groups, and retarded by electron-donating ones. Quantum mechanical calculations was used in order to describe the mechanism of the photocatalytic oxidation reactions of investigated dyes and interpret their reactivities within the framework of the Density Functional Theory (DFT). According to DFT based reactivity descriptors, i.e. Fukui functions and local softness, the active site moves from azo nitrogen atom linked to benzene ring to pyridone carbon atom linked to azo bond, going from dyes with electron-donating groups to dyes with electron-withdrawing groups.

  11. Quantitative structure-activity relationship analysis of substituted arylazo pyridone dyes in photocatalytic system: Experimental and theoretical study

    International Nuclear Information System (INIS)

    Dostanić, J.; Lončarević, D.; Zlatar, M.; Vlahović, F.; Jovanović, D.M.

    2016-01-01

    Highlights: • Electronic effects of para substituted arylazo pyridone dyes. • Linear relationship between Hammett σ_p constants and dyes photoreactivity. • The photocatalytic reactions facilitated by el.-acceptors and retarded by el.-donors. • Fukui functions to analyze the reactivity on concurrent sites within a molecule. • Hydroxyl radicals sustain attack from two reaction sites, depending on a substituent type. - Abstract: A series of arylazo pyridone dyes was synthesized by changing the type of the substituent group in the diazo moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The structural and electronic properties of the investigated dyes was calculated at the M062X/6-31 + G(d,p) level of theory. The observed good linear correlations between atomic charges and Hammett σ_p constants provided a basis to discuss the transmission of electronic substituent effects through a dye framework. The reactivity of synthesized dyes was tested through their decolorization efficiency in TiO_2 photocatalytic system (Degussa P-25). Quantitative structure-activity relationship analysis revealed a strong correlation between reactivity of investigated dyes and Hammett substituent constants. The reaction was facilitated by electron-withdrawing groups, and retarded by electron-donating ones. Quantum mechanical calculations was used in order to describe the mechanism of the photocatalytic oxidation reactions of investigated dyes and interpret their reactivities within the framework of the Density Functional Theory (DFT). According to DFT based reactivity descriptors, i.e. Fukui functions and local softness, the active site moves from azo nitrogen atom linked to benzene ring to pyridone carbon atom linked to azo bond, going from dyes with electron-donating groups to dyes with electron-withdrawing groups.

  12. The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

    Science.gov (United States)

    Nobmann, Patricia; Smith, Aoife; Dunne, Julie; Henehan, Gary; Bourke, Paula

    2009-01-15

    Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

  13. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint.

  14. Investigation of Antileishmanial Activities of Acridines Derivatives against Promastigotes and Amastigotes Form of Parasites Using Quantitative Structure Activity Relationship Analysis

    Directory of Open Access Journals (Sweden)

    Samir Chtita

    2016-01-01

    Full Text Available In a search of newer and potent antileishmanial (against promastigotes and amastigotes form of parasites drug, a series of 60 variously substituted acridines derivatives were subjected to a quantitative structure activity relationship (QSAR analysis for studying, interpreting, and predicting activities and designing new compounds by using multiple linear regression and artificial neural network (ANN methods. The used descriptors were computed with Gaussian 03, ACD/ChemSketch, Marvin Sketch, and ChemOffice programs. The QSAR models developed were validated according to the principles set up by the Organisation for Economic Co-operation and Development (OECD. The principal component analysis (PCA has been used to select descriptors that show a high correlation with activities. The univariate partitioning (UP method was used to divide the dataset into training and test sets. The multiple linear regression (MLR method showed a correlation coefficient of 0.850 and 0.814 for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. Internal and external validations were used to determine the statistical quality of QSAR of the two MLR models. The artificial neural network (ANN method, considering the relevant descriptors obtained from the MLR, showed a correlation coefficient of 0.933 and 0.918 with 7-3-1 and 6-3-1 ANN models architecture for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. The applicability domain of MLR models was investigated using simple and leverage approaches to detect outliers and outsides compounds. The effects of different descriptors in the activities were described and used to study and design new compounds with higher activities compared to the existing ones.

  15. Stereodivergent Synthesis of 1,3-Syn-Polyol Natural Product for Stereochemical-Based Structure Activity Relationship Studies

    Science.gov (United States)

    Zheng, Jiamin

    The 1,3-syn-diol functionality is very common in many natural products. An important class containing this moiety are the 1,3-syn-polyol/pyranone natural products, which have been isolated from a variety of plant sources, and possess biological activities like plant growth inhibition as well as antifeedant, antifungal, antibacterial, and antitumor properties. The feature of this class is a 6-membered lactone where the lactoe oxygen is part of a 1,3-syn-diol motif. To pursue the 1,3-syn-polyol/pyranone natural products, an iterative hydration of polyene strategy was utilized to provide the 1,3- syn-diol functionality, and asymmetric synthetic strategies were explored to form the requisite stereochemistry. The versatility of the asymmetric approach was demonstrated in the synthesis of eupatorium pyranone and also in an ongoing project aimed at the synthesis of SIA7248. As an outgrowth of our work on the total syntheses of 1,3-syn -polyol natural products inspired a stereo-divergent synthesis of 1,3-syn-polyol natural products and their analogs for stereochemical-based structure-activity relationship (SSAR) studies. To identify the key structural factors important for the anticancer activity of the 1,3-syn-polyol/pyranones, a stereo-divergent 16-member library of pyranone/polyol congeners was designed, synthesized and tested with variations in both stereochemistry and numbers of polyol repeat units. Having access to stereochemical isomers of the biologically active natural products allowed us to design experiments that help illustrate their mechanisms of action.

  16. A structure-activity relationship study on antiosteoclastogenesis effect of triterpenoids from the leaves of loquat (Eriobotrya japonica).

    Science.gov (United States)

    Tan, Hui; Ashour, Ahmed; Katakura, Yoshinori; Shimizu, Kuniyoshi

    2015-04-15

    Our previous results elucidated that the leaves of Eriobotrya japonica possessed the potential to suppress ovariectomy-induced bone mineral density deterioration, and ursolic acid, the major bioactive component in these leaves, suppressed the osteoclast differentiation. The aim of this study was to discover more candidates for development of novel antiosteoclastogenesis agents from the leaves of E. japonica. Phytochemical analysis following a cell-based osteoclastic tartrate-resistant acid phosphatase (TRAP) activity assay revealed 11 more compounds with a potent antiosteoclastogenesis effect. The potency of ursane-type triterpenoids from the leaves of E. japonica prompted us to investigate the structure-activity relationships underlying their antiosteoclastogenesis. The results revealed that both the hydroxyl group at C-3 and the carboxylic group at C-17 played indispensable roles in the antiosteoclastogenesis activity of ursane-type triterpenoids. The configuration at C-3 (a beta-form of the hydroxyl group) was found to be important for this activity. While introducing a hydroxyl group at C-19 increased the inhibitory activity of ursane-type triterpenoids carrying an alpha-form hydroxyl group at C-3. The bioactivity analyses of ursolic acid and oleanolic acid demonstrated that the antiosteoclastogenesis effect of ursolic acid may be related to different positions of the C-29 and C-30 methyl groups on the E-ring, since oleanolic acid showed limited activity. The addition of a hydroxyl group at C-2 would dramatically improve the inhibition of oleanane-type triterpenoids. Collectively, these findings could provide important clues for the improvement of multi-targeted antiosteoclastogenesis agents from the leaves of E. japonica. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. Characteristics of chemical binding to alpha 2u-globulin in vitro--evaluating structure-activity relationships

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Miller, A.B.; Bowen, J.P.; Swenberg, J.A.

    1991-01-01

    alpha 2u-Globulin (alpha 2u) has been shown to accumulate in the kidneys of male rats treated with 2,2,4-trimethylpentane (TMP). 2,4,4-Trimethyl-2-pentanol (TMP-2-OH), a metabolite of TMP, is found reversibly bound to alpha 2u isolated from the kidneys of these treated rats. The objectives of the following study were to characterize the ability of [3H]TMP-2-OH to bind to alpha 2u in vitro and to determine whether other compounds that cause this protein to accumulate have the same binding characteristics. Although compounds that have been shown to cause the accumulation of alpha 2u in male rat kidneys compete in vitro with [3H]TMP-2-OH for binding to alpha 2u, they do so to varying degrees. The binding affinity (Kd) of the [3H]TMP-2-OH-alpha 2u complex was calculated to be on the order of 10(-7) M. The inhibition constant values (Ki) determined for d-limonene, 1,4-dichlorobenzene, and 2,5-dichlorophenol were all in the range 10(-4) M, whereas the Ki values for isophorone, 2,4,4- or 2,2,4-trimethyl-1-pentanol, and d-limonene oxide were determined to be in the range 10(-6) and 10(-7) M, respectively. TMP and 2,4,4- and 2,2,4-trimethylpentanoic acid did not compete for binding. This suggests that other factors, besides binding, are involved in the accumulation of alpha 2u. In this study the ability of a chemical to bind to alpha 2u was used as a measure of biological activity to assess structure-activity relationships among the chemicals tested and known to cause the accumulation of alpha 2u. The results so far suggest that binding is dependent on both hydrophobic interactions and hydrogen bonding

  18. Reactions of OH radicals with 2-methyl-1-butyl, neopentyl and 1-hexyl nitrates. Structure-activity relationship for gas-phase reactions of OH with alkyl nitrates: An update

    Science.gov (United States)

    Bedjanian, Yuri; Morin, Julien; Romanias, Manolis N.

    2018-05-01

    The kinetics of the reactions 2-methyl-1-butyl (2M1BNT), neopentyl (NPTNT) and 1-hexyl nitrates (1HXNT) with OH radicals has been studied using a low pressure flow tube reactor combined with a quadrupole mass spectrometer. The rate constants of the title reactions were determined under pseudo-first order conditions from kinetics of OH consumption in excess of nitrates. The overall rate coefficients, k2M1BNT = 1.54 × 10-14 (T/298)4.85 exp (1463/T) (T = 278-538 K), kNPTNT = 1.39 × 10-14 (T/298)4.89 exp (1189/T) (T = 278-500 K) and k1HXNT = 2.23 × 10-13 (T/298)2.83 exp (853/T) cm3molecule-1s-1 (T = 306-538 K) (with conservative 15% uncertainty), were determined at a total pressure of 1 Torr of helium. The yield of trimethylacetaldehyde ((CH3)3CCHO), resulting from the abstraction by OH of an α-hydrogen atom in neopentyl nitrate, followed by α-substituted alkyl radical decomposition, was determined as 0.31 ± 0.06 at T = 298 K. The calculated tropospheric lifetimes of 2M1BNT, NPTNT and 1HXNT indicate that reaction of these nitrates with OH represents an important sink of these compounds in the atmosphere. Based on the available kinetic data, we have updated the structure-activity relationship (SAR) for reactions of alkyl nitrates with OH at T = 298 K. Good agreement (within 20%) is obtained between experimentally measured rate constants (total and that for H-atom abstraction from α carbon) and those calculated from SAR using new substituents factors for almost all the experimental data available.

  19. Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms.

    Science.gov (United States)

    Sun, Wei; Li, Zirong; Shi, Zhengcai; Wang, Bailiang; Gao, Fuqiang; Yang, Yurun; Guo, Wanshou

    2014-05-01

    To explore the correlation between post-severe acute respiratory symptom (SARS) patients with osteonecrosis, investigate the etiology of post-SARS osteonecrosis and select the sensitive molecular symbols for early diagnosis and distinguish the high-risk population. The studied subjects were divided into two groups. Sixty-two post-SARS patients with osteonecrosis were one group, and 52 age- and sex-matched healthy people were as normal controlled group. Empty stomach blood samples from cubital veins were collected from both groups. Plasminogen activator inhibitor (PAI) by means of enzyme-linked immunosorbent assay and PAI-1 4G/5G polymorphism was detected by polymerase chain reaction and solid phase oligonucleotide assay. The blood agents of post-SARS patients changed obviously with 15.64 ± 13.85 U/ml while the control group 7.96 ± 4.27 U/ml; 4G/4G genotype for the PAI-1 polymorphism detected in post-SARS group was more than that of the control group, but had no statistical significance. The plasma PAI activity was related to homozygote 4G/4G genotype. This reveals that homozygote 4G/4G genotype may be a susceptible gene mark to Chinese osteonecrosis patients. Plasminogen activator inhibitor-1 is sensitive blood symbol for screening high-risk susceptible population; 4G/4G PAI-1 genotype may be an etiological factor in osteonecrosis.

  20. Quantitative structure-activity relationship study of antioxidative peptide by using different sets of amino acids descriptors

    Science.gov (United States)

    Li, Yao-Wang; Li, Bo; He, Jiguo; Qian, Ping

    2011-07-01

    A database consisting of 214 tripeptides which contain either His or Tyr residue was applied to study quantitative structure-activity relationships (QSAR) of antioxidative tripeptides. Partial Least-Squares Regression analysis (PLSR) was conducted using parameters individually of each amino acid descriptor, including Divided Physico-chemical Property Scores (DPPS), Hydrophobic, Electronic, Steric, and Hydrogen (HESH), Vectors of Hydrophobic, Steric, and Electronic properties (VHSE), Molecular Surface-Weighted Holistic Invariant Molecular (MS-WHIM), isotropic surface area-electronic charge index (ISA-ECI) and Z-scale, to describe antioxidative tripeptides as X-variables and antioxidant activities measured with ferric thiocyanate methods were as Y-variable. After elimination of outliers by Hotelling's T 2 method and residual analysis, six significant models were obtained describing the entire data set. According to cumulative squared multiple correlation coefficients ( R2), cumulative cross-validation coefficients ( Q2) and relative standard deviation for calibration set (RSD c), the qualities of models using DPPS, HESH, ISA-ECI, and VHSE descriptors are better ( R2 > 0.6, Q2 > 0.5, RSD c 0.44). Furthermore, the predictive ability of models using DPPS descriptor is best among the six descriptors systems (cumulative multiple correlation coefficient for predict set ( Rext2) > 0.7). It was concluded that the DPPS is better to describe the amino acid of antioxidative tripeptides. The results of DPPS descriptor reveal that the importance of the center amino acid and the N-terminal amino acid are far more than the importance of the C-terminal amino acid for antioxidative tripeptides. The hydrophobic (positively to activity) and electronic (negatively to activity) properties of the N-terminal amino acid are suggested to play the most important significance to activity, followed by the hydrogen bond (positively to activity) of the center amino acid. The N-terminal amino acid

  1. The influence of R and S configurations of a series of amphetamine derivatives on quantitative structure-activity relationship models

    Energy Technology Data Exchange (ETDEWEB)

    Fresqui, Maira A.C., E-mail: maira@iqsc.usp.br [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil); Ferreira, Marcia M.C., E-mail: marcia@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, POB 6154, 13083-970 Campinas, SP (Brazil); Trsic, Milan, E-mail: cra612@gmail.com [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil)

    2013-01-08

    Highlights: Black-Right-Pointing-Pointer The QSAR model is not dependent of ligand conformation. Black-Right-Pointing-Pointer Amphetamines were analyzed by quantum chemical, steric and hydrophobic descriptors. Black-Right-Pointing-Pointer CHELPG atomic charges on the benzene ring are one of the most important descriptors. Black-Right-Pointing-Pointer The PLS models built were extensively validated. Black-Right-Pointing-Pointer Manual docking supports the QSAR results by pi-pi stacking interactions. - Abstract: Chiral molecules need special attention in drug design. In this sense, the R and S configurations of a series of thirty-four amphetamines were evaluated by quantitative structure-activity relationship (QSAR). This class of compounds has antidepressant, anti-Parkinson and anti-Alzheimer effects against the enzyme monoamine oxidase A (MAO A). A set of thirty-eight descriptors, including electronic, steric and hydrophobic ones, were calculated. Variable selection was performed through the correlation coefficients followed by the ordered predictor selection (OPS) algorithm. Six descriptors (CHELPG atomic charges C3, C4 and C5, electrophilicity, molecular surface area and log P) were selected for both configurations and a satisfactory model was obtained by PLS regression with three latent variables with R{sup 2} = 0.73 and Q{sup 2} = 0.60, with external predictability Q{sup 2} = 0.68, and R{sup 2} = 0.76 and Q{sup 2} = 0.67 with external predictability Q{sup 2} = 0.50, for R and S configurations, respectively. To confirm the robustness of each model, leave-N-out cross validation (LNO) was carried out and the y-randomization test was used to check if these models present chance correlation. Moreover, both automated or a manual molecular docking indicate that the reaction of ligands with the enzyme occurs via pi-pi stacking interaction with Tyr407, inclined face-to-face interaction with Tyr444, while aromatic hydrogen-hydrogen interactions with Tyr197 are preferable

  2. Discovery and preliminary structure-activity relationship of the marine natural product manzamines as herpes simplex virus type-1 inhibitors.

    Science.gov (United States)

    Palem, Jayavardhana R; Mudit, Mudit; Hsia, Shao-Chung V; Sayed, Khalid A El

    2017-01-01

    Herpes simplex virus type-1 (HSV-1) is a member of alpha-herpesviridae family and is known to cause contagious human infections. The marine habitat is a rich source of structurally unique bioactive secondary metabolites. A small library of marine natural product classes 1-10 has been screened to discover a new hit entity active against HSV-1. Manzamine A showed potent activity against HSV-1 via targeting the viral gene ICP0. Manzamine A is a β-carboline alkaloid isolated from the Indo-Pacific sponge Acanthostrongylophora species. Currently, acyclovir is the drug of choice for HSV-1 infections. Compared with 50 µM acyclovir, manzamine A at 1 µM concentration produced potent repressive effects on viral replication and release of infectious viruses in SIRC cells in recent studies. The potent anti-HSV-1 activity of manzamine A prompted a preliminary structure-activity relationship study by testing targeted manzamines. These included 8-hydroxymanzamine A (11), to test the effect of the C-8 hydroxy substitution at the β-carboline moiety; manzamine E (12), to assess the importance of substitution at the azacyclooctane ring; and ircinal A (13), to determine whether the β-carboline ring is required for the activity. Manzamine A was chemically transformed to its salt forms, manzamine A monohydrochloride (14) and manzamine A monotartrate (15), to test whether improving water solubility and hydrophilicity will positively affect the activity. Compounds were tested for activity against HSV-1 using fluorescent microscopy and plaque assay. The results showed the reduced anti-HSV-1 activity of 11, suggesting that C-8 hydroxy substitution might adversely affect the activity. Similarly, manzamines 12 and 13 showed no activity against HSV-1, indicating the preference of the unsubstituted azacylcooctane and β-carboline rings to the activity. Anti-HSV-1 activity was significantly improved for the manzamine A salts 14 and 15, suggesting that improving the overall water solubility

  3. Discovery and structure-activity relationships of (2-(arylthio)benzylideneamino)guanidines as a novel series of potent apoptosis inducers.

    Science.gov (United States)

    Zhang, Han-Zhong; Crogan-Grundy, Candace; May, Chris; Drewe, John; Tseng, Ben; Cai, Sui Xiong

    2009-04-01

    1-(2-(2,5-Dimethoxyphenylthio)benzylidene)semicarbazide (2a) was discovered as a potent apoptosis inducer through our cell based HTS assay. SAR study led to the discovery of a more aqueous soluble analog (2-(2,5-dimethoxyphenylthio)-6-methoxybenzylideneamino)guanidine (5e) with EC(50) value of 60 nM in the caspase activation assay and GI(50) value of 62 nM in the growth inhibition assay in T47D cells. Compound 5e was found to be an inhibitor of tubulin polymerization and efficacious in a MX-1 breast tumor model.

  4. Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents.

    Science.gov (United States)

    Aratikatla, Eswar K; Valkute, Tushar R; Puri, Sunil K; Srivastava, Kumkum; Bhattacharya, Asish K

    2017-09-29

    Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC 50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3-57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC 50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC 50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC 50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1

  5. Effect of O-methylated and glucuronosylated flavonoids from Tamarix gallica on α-glucosidase inhibitory activity: structure-activity relationship and synergistic potential.

    Science.gov (United States)

    Ben Hmidene, Asma; Smaoui, Abderrazak; Abdelly, Chedly; Isoda, Hiroko; Shigemori, Hideyuki

    2017-03-01

    O-Methylated and glucuronosylated flavonoids were isolated from Tamarix gallica as α-glucosidase inhibitors. Structure-activity relationship of these flavonoids suggests that catechol moiety and glucuronic acid at C-3 are factors in the increase in α-glucosidase inhibitory activity. Furthermore, rhamnetin, tamarixetin, rhamnazin, KGlcA, KGlcA-Me, QGlcA, and QGlcA-Me exhibit synergistic potential when applied with a very low concentration of acarbose to α-glucosidase from rat intestine.

  6. Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.

    Science.gov (United States)

    Hu, Yi; Ma, Lifu; Wu, Min; Wong, Melissa S; Li, Bei; Corral, Sergio; Yu, Zhizhou; Nomanbhoy, Tyzoon; Alemayehu, Senaiet; Fuller, Stacy R; Rosenblum, Jonathan S; Rozenkrants, Natasha; Minimo, Lauro C; Ripka, William C; Szardenings, Anna K; Kozarich, John W; Shreder, Kevin R

    2005-10-01

    The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

  7. 2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Xin-Juan Yang

    2013-08-01

    Full Text Available The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs. In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 2–12 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.

  8. Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba: Isolation, modification, and structure-activity relationship study.

    Science.gov (United States)

    Guo, Yan-Qiong; Tang, Gui-Hua; Lou, Lan-Lan; Li, Wei; Zhang, Bei; Liu, Bo; Yin, Sheng

    2018-01-20

    The bioassay-guided phytochemical study of a traditional Chinese medicine Morus alba led to the isolation of 18 prenylated flavonoids (1-18), of which (±)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC 50 values ranging from 0.0054 to 0.40 μM, being more active than the positive control rolipram (IC 50  = 0.62 μM). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

    Science.gov (United States)

    Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

    2016-07-25

    We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

  10. Structure-activity relationship of the ionic cocrystal: 5-amino-2-naphthalene sulfonate·ammonium ions for pharmaceutical applications

    Science.gov (United States)

    Sangeetha, M.; Mathammal, R.

    2018-02-01

    The ionic cocrystals of 5-amino-2-naphthalene sulfonate · ammonium ions (ANSA-ṡNH4+) were grown under slow evaporation method and examined in detail for pharmaceutical applications. The crystal structure and intermolecular interactions were studied from the single X-ray diffraction analysis and the Hirshfeld surfaces. The 2D fingerprint plots displayed the inter-contacts possible in the ionic crystal. Computational DFT method was established to determine the structural, physical and chemical properties. The molecular geometries obtained from the X-ray studies were compared with the optimized geometrical parameters calculated using DFT/6-31 + G(d,p) method. The band gap energy calculated from the UV-Visible spectral analysis and the HOMO-LUMO energy gap are compared. The theoretical UV-Visible calculations helped in determining the type of electronic transition taking place in the title molecule. The maximum absorption bands and transitions involved in the molecule represented the drug reaction possible. Non-linear optical properties were characterized from SHG efficiency measurements experimentally and the NLO parameters are also calculated from the optimized structure. The reactive sites within the molecule are detailed from the MEP surface maps. The molecular docking studies evident the structure-activity of the ionic cocrystal for anti-cancer drug property.

  11. Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

    Science.gov (United States)

    Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

    2015-07-15

    Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Structure-activity relationship of prenyl-substituted polyphenols from Artocarpus heterophyllus as inhibitors of melanin biosynthesis in cultured melanoma cells.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2007-09-01

    A series of prenylated, flavone-based polyphenols, compounds 1-8, were isolated from the wood of Artocarpus heterophyllus. These compounds, which have previously been shown not to inhibit tyrosinase activity, were found to be active inhibitors of the in vivo melanin biosynthesis in B16 melanoma cells, with little or no cytotoxicity. To clarify the structural requirement for inhibition, some structure-activity relationships were studied, in comparison with related compounds lacking prenyl side chains. Our experiments indicate that both prenyl and OH groups, as well as the type of substitution pattern, are crucial for the inhibition of melanin production in B16 melanoma cells.

  13. Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery.

    Science.gov (United States)

    Quiliano, Miguel; Pabón, Adriana; Moles, Ernest; Bonilla-Ramirez, Leonardo; Fabing, Isabelle; Fong, Kim Y; Nieto-Aco, Diego A; Wright, David W; Pizarro, Juan C; Vettorazzi, Ariane; López de Cerain, Adela; Deharo, Eric; Fernández-Busquets, Xavier; Garavito, Giovanny; Aldana, Ignacio; Galiano, Silvia

    2018-05-25

    Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC 50 s activity in chloroquine-sensitive and multidrug-resistant strains (IC 50 s antimalarial compounds. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. PLS-based quantitative structure-activity relationship for substituted benzamides of clebopride type. Application of experimental design in drug design.

    Science.gov (United States)

    Norinder, U; Högberg, T

    1992-04-01

    The advantageous approach of using an experimentally designed training set as the basis for establishing a quantitative structure-activity relationship with good predictive capability is described. The training set was selected from a fractional factorial design scheme based on a principal component description of physico-chemical parameters of aromatic substituents. The derived model successfully predicts the activities of additional substituted benzamides of 6-methoxy-N-(4-piperidyl)salicylamide type. The major influence on activity of the 3-substituent is demonstrated.

  15. Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A role played by the lactone moiety.

    Science.gov (United States)

    Qiu, Haibo; Qian, Shan; Head, Sarah A; Liu, Jun O; Jin, Zhendong

    2016-10-01

    Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-109 was designed and synthesized to probe the importance of the lactone moiety of the molecule by replacing the lactone in ZJ-101 with a lactam. The biological evaluation showed that ZJ-109 is about 8-12 times less active against cancer cells in vitro than ZJ-101, suggesting that the lactone moiety of the molecule is important for its anticancer activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Structure-activity relationships of the unique and potent agouti-related protein (AGRP)-melanocortin chimeric Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH2 peptide template.

    Science.gov (United States)

    Wilczynski, Andrzej; Wilson, Krista R; Scott, Joseph W; Edison, Arthur S; Haskell-Luevano, Carrie

    2005-04-21

    The melanocortin receptor system consists of endogenous agonists, antagonists, G-protein coupled receptors, and auxiliary proteins that are involved in the regulation of complex physiological functions such as energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. Herein, we report the structure-activity relationship (SAR) of a new chimeric hAGRP-melanocortin agonist peptide template Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) that was characterized using amino acids previously reported in other melanocortin agonist templates. Twenty peptides were examined in this study, and six peptides were selected for (1)H NMR and computer-assisted molecular modeling structural analysis. The most notable results include the identification that modification of the chimeric template at the His position with Pro and Phe resulted in ligands that were nM mouse melanocortin-3 receptor (mMC3R) antagonists and nM mouse melanocortin-4 receptor (mMC4R) agonists. The peptides Tyr-c[beta-Asp-His-DPhe-Ala-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) and Tyr-c[beta-Asp-His-DNal(1')-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) resulted in 730- and 560-fold, respectively, mMC4R versus mMC3R selective agonists that also possessed nM agonist potency at the mMC1R and mMC5R. Structural studies identified a reverse turn occurring in the His-DPhe-Arg-Trp domain, with subtle differences observed that may account for the differences in melanocortin receptor pharmacology. Specifically, a gamma-turn secondary structure involving the DPhe(4) in the central position of the Tyr-c[beta-Asp-Phe-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) peptide may differentiate the mixed mMC3R antagonist and mMC4R agonist pharmacology.

  17. Nano(Q)SAR: Challenges, pitfalls and perspectives.

    Science.gov (United States)

    Tantra, Ratna; Oksel, Ceyda; Puzyn, Tomasz; Wang, Jian; Robinson, Kenneth N; Wang, Xue Z; Ma, Cai Y; Wilkins, Terry

    2015-01-01

    Regulation for nanomaterials is urgently needed, and the drive to adopt an intelligent testing strategy is evident. Such a strategy will not only provide economic benefits but will also reduce moral and ethical concerns arising from animal testing. For regulatory purposes, such an approach is promoted by REACH, particularly the use of quantitative structure-activity relationships [(Q)SAR] as a tool for the categorisation of compounds according to their physicochemical and toxicological properties. In addition to compounds, (Q)SAR has also been applied to nanomaterials in the form of nano(Q)SAR. Although (Q)SAR in chemicals is well established, nano(Q)SAR is still in early stages of development and its successful uptake is far from reality. This article aims to identify some of the pitfalls and challenges associated with nano-(Q)SARs in relation to the categorisation of nanomaterials. Our findings show clear gaps in the research framework that must be addressed if we are to have reliable predictions from such models. Three major barriers were identified: the need to improve quality of experimental data in which the models are developed from, the need to have practical guidelines for the development of the nano(Q)SAR models and the need to standardise and harmonise activities for the purpose of regulation. Of these three, the first, i.e. the need to improve data quality requires immediate attention, as it underpins activities associated with the latter two. It should be noted that the usefulness of data in the context of nano-(Q)SAR modelling is not only about the quantity of data but also about the quality, consistency and accessibility of those data.

  18. Inhibitors of inosine monophosphate dehydrogenase: SARs about the N-[3-Methoxy-4-(5-oxazolyl)phenyl moiety.

    Science.gov (United States)

    Iwanowicz, Edwin J; Watterson, Scott H; Guo, Junqing; Pitts, William J; Murali Dhar, T G; Shen, Zhongqi; Chen, Ping; Gu, Henry H; Fleener, Catherine A; Rouleau, Katherine A; Cheney, Daniel L; Townsend, Robert M; Hollenbaugh, Diane L

    2003-06-16

    The first reported structure-activity relationships (SARs) about the N-[3-methoxy-4-(5-oxazolyl)phenyl moiety for a series of recently disclosed inosine monophosphate dehydrogenase (IMPDH) inhibitors are described. The syntheses and in vitro inhibitory values for IMPDH II, and T-cell proliferation (for select analogues) are given.

  19. Quantitative structure-activity relationship (QSAR) models for polycyclic aromatic hydrocarbons (PAHs) dissipation in rhizosphere based on molecular structure and effect size

    International Nuclear Information System (INIS)

    Ma Bin; Chen Huaihai; Xu Minmin; Hayat, Tahir; He Yan; Xu Jianming

    2010-01-01

    Rhizoremediation is a significant form of bioremediation for polycyclic aromatic hydrocarbons (PAHs). This study examined the role of molecular structure in determining the rhizosphere effect on PAHs dissipation. Effect size in meta-analysis was employed as activity dataset for building quantitative structure-activity relationship (QSAR) models and accumulative effect sizes of 16 PAHs were used for validation of these models. Based on the genetic algorithm combined with partial least square regression, models for comprehensive dataset, Poaceae dataset, and Fabaceae dataset were built. The results showed that information indices, calculated as information content of molecules based on the calculation of equivalence classes from the molecular graph, were the most important molecular structural indices for QSAR models of rhizosphere effect on PAHs dissipation. The QSAR model, based on the molecular structure indices and effect size, has potential to be used in studying and predicting the rhizosphere effect of PAHs dissipation. - Effect size based on meta-analysis was used for building PAHs dissipation quantitative structure-activity relationship (QSAR) models.

  20. Quantitative structure-activity relationship (QSAR) models for polycyclic aromatic hydrocarbons (PAHs) dissipation in rhizosphere based on molecular structure and effect size

    Energy Technology Data Exchange (ETDEWEB)

    Ma Bin; Chen Huaihai; Xu Minmin; Hayat, Tahir [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China); He Yan, E-mail: yhe2006@zju.edu.c [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China); Xu Jianming, E-mail: jmxu@zju.edu.c [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China)

    2010-08-15

    Rhizoremediation is a significant form of bioremediation for polycyclic aromatic hydrocarbons (PAHs). This study examined the role of molecular structure in determining the rhizosphere effect on PAHs dissipation. Effect size in meta-analysis was employed as activity dataset for building quantitative structure-activity relationship (QSAR) models and accumulative effect sizes of 16 PAHs were used for validation of these models. Based on the genetic algorithm combined with partial least square regression, models for comprehensive dataset, Poaceae dataset, and Fabaceae dataset were built. The results showed that information indices, calculated as information content of molecules based on the calculation of equivalence classes from the molecular graph, were the most important molecular structural indices for QSAR models of rhizosphere effect on PAHs dissipation. The QSAR model, based on the molecular structure indices and effect size, has potential to be used in studying and predicting the rhizosphere effect of PAHs dissipation. - Effect size based on meta-analysis was used for building PAHs dissipation quantitative structure-activity relationship (QSAR) models.

  1. Quantitative structure-activity relationship analysis to elucidate the clearance mechanisms of Tc-99m labeled quinolone antibiotics

    International Nuclear Information System (INIS)

    Salahinejad, M.; Mirshojaei, S.F.

    2016-01-01

    This study aims to establish molecular modeling methods for predicting the liver and kidney uptakes of Tc-99m labeled quinolone antibiotics. Some three-dimensional quantitative-activity relationships (3D-QSAR) models were developed using comparative molecular field analysis and grid-independent descriptors procedures. As a first report on 3D-QSAR modeling, the predicted liver and kidney uptakes for quinolone antibiotics were in good agreement with the experimental values. The obtained results confirm the importance of hydrophobic interactions, size and steric hindrance of antibiotic molecules in their liver uptakes, while the electrostatic interactions and hydrogen bonding ability have impressive effects on their kidney uptakes. (author)

  2. Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.

    Science.gov (United States)

    Perucca, Paola; Savio, Monica; Cazzalini, Ornella; Mocchi, Roberto; Maccario, Cristina; Sommatis, Sabrina; Ferraro, Daniela; Pizzala, Roberto; Pretali, Luca; Fasani, Elisa; Albini, Angelo; Stivala, Lucia Anna

    2014-11-01

    The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O₂ partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Structure-Activity Relationship Study of Sesquiterpene Lactones and Their Semi-Synthetic Amino Derivatives as Potential Antitrypanosomal Products

    Directory of Open Access Journals (Sweden)

    Stefanie Zimmermann

    2014-03-01

    Full Text Available Sesquiterpene lactones (STLs are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness and mammalian cancer cells (rat bone myoblast L6 cells. It was found that the α-methylene-γ-lactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity is facilitated by 2-(hydroxymethylacrylate or 3,4-dihydroxy-2-methylenebutylate side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL amines with morpholino and dimethylamino groups showed improved in vitro activity over the native STLs. The dimethylamino derivative of cynaropicrin was prepared and tested orally in the T. b. rhodesiense acute mouse model, where it showed reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity.

  4. Quantitative structure activity relationships (QSAR) for binary mixtures at non-equitoxic ratios based on toxic ratios-effects curves.

    Science.gov (United States)

    Tian, Dayong; Lin, Zhifen; Yin, Daqiang

    2013-01-01

    The present study proposed a QSAR model to predict joint effects at non-equitoxic ratios for binary mixtures containing reactive toxicants, cyanogenic compounds and aldehydes. Toxicity of single and binary mixtures was measured by quantifying the decrease in light emission from the Photobacterium phosphoreum for 15 min. The joint effects of binary mixtures (TU sum) can thus be obtained. The results showed that the relationships between toxic ratios of the individual chemicals and their joint effects can be described by normal distribution function. Based on normal distribution equations, the joint effects of binary mixtures at non-equitoxic ratios ( [Formula: see text]) can be predicted quantitatively using the joint effects at equitoxic ratios ( [Formula: see text]). Combined with a QSAR model of [Formula: see text]in our previous work, a novel QSAR model can be proposed to predict the joint effects of mixtures at non-equitoxic ratios ( [Formula: see text]). The proposed model has been validated using additional mixtures other than the one used for the development of the model. Predicted and observed results were similar (p>0.05). This study provides an approach to the prediction of joint effects for binary mixtures at non-equitoxic ratios.

  5. Development of quantitative structure activity relationship (QSAR) model for disinfection byproduct (DBP) research: A review of methods and resources

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Baiyang, E-mail: poplar_chen@hotmail.com [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China); Zhang, Tian [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China); Bond, Tom [Department of Civil and Environmental Engineering, Imperial College, London SW7 2AZ (United Kingdom); Gan, Yiqun [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China)

    2015-12-15

    Quantitative structure–activity relationship (QSAR) models are tools for linking chemical activities with molecular structures and compositions. Due to the concern about the proliferating number of disinfection byproducts (DBPs) in water and the associated financial and technical burden, researchers have recently begun to develop QSAR models to investigate the toxicity, formation, property, and removal of DBPs. However, there are no standard procedures or best practices regarding how to develop QSAR models, which potentially limit their wide acceptance. In order to facilitate more frequent use of QSAR models in future DBP research, this article reviews the processes required for QSAR model development, summarizes recent trends in QSAR-DBP studies, and shares some important resources for QSAR development (e.g., free databases and QSAR programs). The paper follows the four steps of QSAR model development, i.e., data collection, descriptor filtration, algorithm selection, and model validation; and finishes by highlighting several research needs. Because QSAR models may have an important role in progressing our understanding of DBP issues, it is hoped that this paper will encourage their future use for this application.

  6. Development of quantitative structure activity relationship (QSAR) model for disinfection byproduct (DBP) research: A review of methods and resources

    International Nuclear Information System (INIS)

    Chen, Baiyang; Zhang, Tian; Bond, Tom; Gan, Yiqun

    2015-01-01

    Quantitative structure–activity relationship (QSAR) models are tools for linking chemical activities with molecular structures and compositions. Due to the concern about the proliferating number of disinfection byproducts (DBPs) in water and the associated financial and technical burden, researchers have recently begun to develop QSAR models to investigate the toxicity, formation, property, and removal of DBPs. However, there are no standard procedures or best practices regarding how to develop QSAR models, which potentially limit their wide acceptance. In order to facilitate more frequent use of QSAR models in future DBP research, this article reviews the processes required for QSAR model development, summarizes recent trends in QSAR-DBP studies, and shares some important resources for QSAR development (e.g., free databases and QSAR programs). The paper follows the four steps of QSAR model development, i.e., data collection, descriptor filtration, algorithm selection, and model validation; and finishes by highlighting several research needs. Because QSAR models may have an important role in progressing our understanding of DBP issues, it is hoped that this paper will encourage their future use for this application.

  7. Kinetics and structure-activity relationship of dendritic bridged hindered phenol antioxidants to protect styrene against free radical induced peroxidation

    Science.gov (United States)

    Li, Cui-Qin; Guo, Su-Yue; Wang, Jun; Shi, Wei-Guang; Zhang, Zhi-Qiu; Wang, Peng-Xiang

    2017-12-01

    A series of dendritic poly(amido-amine) (PAMAM) bridged hindered phenols antioxidants were synthesized. The active antioxidant group (3-(3,5-di- tert-butyl-4-hydroxyphenyl)propionic acid) was attached to two generations of PAMAM dendrimers, and their structure was verified by nuclear magnetic resonance (NMR) and fourier transform infrared spectra (FT-IR). The antioxidant abilities of the dendritic phenols to inhibit the oxidation of styrene were evaluated and the relationships between the length of core, the generation of dendrimers and the antioxidant activities were established. The reaction kinetics of scavenging peroxyl radicals was followed by oxygen consumption. The inhibition time ( t inh) values showed the dendritic phenols had the ability of scavenging peroxyl radicals, and that the antioxidant ability increased with the increasing length of the core and the generation. The kinetic analysis demonstrated that dendritic phenols could slow the rate of styrene peroxidation induced by AIBN, as shown by the number of trapping ROO· ( n), and this role was in accordance with that of the t inh values.

  8. Identification of residues important for the activity of aldehyde-deformylating oxygenase through investigation into the structure-activity relationship.

    Science.gov (United States)

    Wang, Qing; Bao, Luyao; Jia, Chenjun; Li, Mei; Li, Jian-Jun; Lu, Xuefeng

    2017-03-16

    Aldehyde-deformylating oxygenase (ADO) is a key enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, cADO (cyanobacterial ADO) showed extreme low activity with the k cat value below 1 min -1 , which would limit its application in biofuel production. To identify the activity related key residues of cADO is urgently required. The amino acid residues which might affect cADO activity were identified based on the crystal structures and sequence alignment of cADOs, including the residues close to the di-iron center (Tyr39, Arg62, Gln110, Tyr122, Asp143 of cADO-1593), the protein surface (Trp 178 of cADO-1593), and those involved in two important hydrogen bonds (Gln49, Asn123 of cADO-1593, and Asp49, Asn123 of cADO-sll0208) and in the oligopeptide whose conformation changed in the absence of the di-iron center (Leu146, Asn149, Phe150 of cADO-1593, and Thr146, Leu148, Tyr150 of cADO-sll0208). The variants of cADO-1593 from Synechococcus elongatus PCC7942 and cADO-sll0208 from Synechocystis sp. PCC6803 were constructed, overexpressed, purified and kinetically characterized. The k cat values of L146T, Q49H/N123H/F150Y and W178R of cADO-1593 and L148R of cADO-sll0208 were increased by more than two-fold, whereas that of R62A dropped by 91.1%. N123H, Y39F and D143A of cADO-1593, and Y150F of cADO-sll0208 reduced activities by ≤ 20%. Some important amino acids, which exerted some effects on cADO activity, were identified. Several enzyme variants exhibited greatly reduced activity, while the k cat values of several mutants are more than two-fold higher than the wild type. This study presents the report on the relationship between amino acid residues and enzyme activity of cADOs, and the information will provide a guide for enhancement of cADO activity through protein engineering.

  9. The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships.

    Science.gov (United States)

    Shaghafi, Michael B; Barrett, David G; Willard, Francis S; Overman, Larry E

    2014-02-15

    We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Structure-Activity Relationship Study of N(6)-Benzoyladenine-Type BRD4 Inhibitors and Their Effects on Cell Differentiation and TNF-α Production.

    Science.gov (United States)

    Amemiya, Seika; Yamaguchi, Takao; Sakai, Taki; Hashimoto, Yuichi; Noguchi-Yachide, Tomomi

    2016-01-01

    Bromodomains are epigenetic 'readers' of histone acetylation. The first potent bromodomain and extra-terminal domain (BET) inhibitors, (+)-JQ1 and I-BET762 (also known as GSK525762), were reported in 2010. Some BET inhibitors are already under clinical trial for the treatment of cancers, but so far, only a few chemical scaffolds are available. We have reported potent N(6)-benzoyladenine-based inhibitors of BRD4, a BET family member that serves as a key mediator of transcriptional elongation. Here we present an analysis of the structure-activity relationships of these inhibitors. Among the compounds examined, 20, 28 and 29 enhanced all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation and inhibited tumor necrosis factor (TNF)-α production by THP-1 cells.

  11. Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells.

    Science.gov (United States)

    Ninomiya, Masayuki; Nishida, Kyohei; Tanaka, Kaori; Watanabe, Kunitomo; Koketsu, Mamoru

    2013-07-01

    Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure-activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

  12. Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

    International Nuclear Information System (INIS)

    Kim, K.H.; Martin, Y.; Otis, E.; Mao, J.

    1989-01-01

    Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125 I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids

  13. Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides.

    Science.gov (United States)

    Du, Shijie; Tian, Zaimin; Yang, Dongyan; Li, Xiuyun; Li, Hong; Jia, Changqing; Che, Chuanliang; Wang, Mian; Qin, Zhaohai

    2015-05-08

    A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

  14. Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

    Directory of Open Access Journals (Sweden)

    Shijie Du

    2015-05-01

    Full Text Available A series of novel 3-(difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-ylphenyl-3-(difluoro-methyl-1-methyl-1H-pyrazole-4-carboxamide (9m exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

  15. SARS - Diagnosis

    Indian Academy of Sciences (India)

    SARS - Diagnosis. Mainly by exclusion of known causes of atypical pneumonia; * X ray Chest; * PCR on body fluids- primers defined by WHO centres available from website.-ve result does not exclude SARS. * Sequencing of amplicons; * Viral Cultures – demanding; * Antibody tests.

  16. Centrally acting serotonergic and dopaminergic agents. 1. Synthesis and structure-activity relationships of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives.

    Science.gov (United States)

    Lin, C H; Haadsma-Svensson, S R; Lahti, R A; McCall, R B; Piercey, M F; Schreur, P J; Von Voigtlander, P F; Smith, M W; Chidester, C G

    1993-04-16

    The synthesis and structure-activity relationships (SAR) of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives (3) are described. These compounds are conformationally restricted, angular tricyclic analogs of 2-aminotetralin. The synthesis was achieved in several steps from the corresponding 2-tetralones. The enantiomers of the cis analogs were obtained from either fractional recrystallizations of the diastereomeric salts of di-p-toluoyl-L-(or D)-tartaric acid or an asymmetric synthesis using chiral (R)-alpha-methylbenzylamine. All analogs were evaluated in the in vitro 5-HT1A and D2 binding assays and selected analogs were investigated further in biochemical and behavioral tests. Analogs with 9-methoxy substitution (R1 in 3) showed mixed 5-HT1A agonist and dopamine antagonist activities whereas the corresponding 9-hydroxy analogs displayed selective 5-HT1A agonist activity. The cis analogs were found to be more potent than the corresponding trans analogs and in the cis series, the (3aR)-(-)-enantiomers displayed higher potency. Nitrogen substitution (R2 in 3) with either an n-propyl or an allyl group produced similar activities whereas replacement with a bulky alpha-methylbenzyl group resulted in loss of activity. Analogs without aromatic substitution (R1 = H in 3) still showed good 5-HT1A agonist activity, although less potent than the 9-methoxy series. In this case, the trans analogs possessed equal or higher in vitro 5-HT1A affinity than the corresponding cis analogs. Analogs with either 6-methoxy or 6-hydroxy substitution (R1 in 3) were found to display dopamine antagonist properties. However, only N-allyl analogs showed this activity. In the 6-methoxy-N-allyl series, the cis analog was found to be more potent than the trans analog. Again, between the pair of cis enantiomers, the (3aR)-(-)-enantiomer showed higher potency. Incorporation of an additional methyl group into 9-methoxy cis analogs at C-2 resulted in retention of potent 5-HT1A agonist activity.

  17. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

    Science.gov (United States)

    Mladenović, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-04-24

    Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including the following: (1) definition of optimized and validated structure-based three-dimensional (3-D) quantitative structure-activity relationships (QSAR) models derived from available cocrystallized inhibitor-MAO B complexes; (2) elaboration of SAR features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61 ) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rule assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSAR training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a

  18. Quinolone-based IMPDH inhibitors: introduction of basic residues on ring D and SAR of the corresponding mono, di and benzofused analogues.

    Science.gov (United States)

    Dhar, T G Murali; Watterson, Scott H; Chen, Ping; Shen, Zhongqi; Gu, Henry H; Norris, Derek; Carlsen, Marianne; Haslow, Kristin D; Pitts, William J; Guo, Junqing; Chorba, John; Fleener, Catherine A; Rouleau, Katherine A; Townsend, Robert; Hollenbaugh, Diane; Iwanowicz, Edwin J

    2003-02-10

    The synthesis and the structure-activity relationships (SAR) of analogues derived from the introduction of basic residues on ring D of quinolone-based inhibitors of IMPDH are described. This led to the identification of compound 27 as a potent inhibitor of IMPDH with significantly improved aqueous solubility over the lead compound 1.

  19. Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species

    Directory of Open Access Journals (Sweden)

    Chiara Cheng Lim

    2009-03-01

    Full Text Available DNA damage by reactive species is associated with susceptibility to chronic human degenerative disorders. Anthocyanins are naturally occurring antioxidants, that may prevent or reverse such damage. There is considerable interest in anthocyanic food plants as good dietary sources, with the potential for reducing susceptibility to chronic disease. While structure-activity relationships have provided guidelines on molecular structure in relation to free hydroxyl- radical scavenging, this may not cover the situation in food plants where the anthocyanins are part of a complex mixture, and may be part of complex structures, including anthocyanic vacuolar inclusions (AVIs. Additionally, new analytical methods have revealed new structures in previously-studied materials. We have compared the antioxidant activities of extracts from six anthocyanin-rich edible plants (red cabbage, red lettuce, blueberries, pansies, purple sweetpotato skin, purple sweetpotato flesh and Maori potato flesh using three chemical assays (DPPH, TRAP and ORAC, and the in vitro Comet assay. Extracts from the flowering plant, lisianthus, were used for comparison. The extracts showed differential effects in the chemical assays, suggesting that closely related structures have different affinities to scavenge different reactive species. Integration of anthocyanins to an AVI led to more sustained radical scavenging activity as compared with the free anthocyanin. All but the red lettuce extract could reduce endogenous DNA damage in HT-29 colon cancer cells. However, while extracts from purple sweetpotato skin and flesh, Maori potato and pansies, protected cells against subsequent challenge by hydrogen peroxide at 0oC, red cabbage extracts were pro-oxidant, while other extracts had no effect. When the peroxide challenge was at 37oC, all of the extracts appeared pro-oxidant. Maori potato extract, consistently the weakest antioxidant in all the chemical assays, was more effective in the

  20. Polybrominated diphenyl ether (PBDE) effects in rat neuronal cultures: 14C-PBDE accumulation, biological effect, and structure-activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, P.R.; Ward, T. [Neurotoxicology Div., NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Burka, T. [National Insts. of Environmental Health Sciences, Research Triangle Park, NC (United States); Ludewig, G.; Robertson, L. [The Univ. of Iowa Coll. of Public Health, Iowa City, IA (United States); Birnbaum, L. [Experimental Toxicology Div., NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2004-09-15

    Polybrominated diphenyl ethers (PBDEs) are used as flame-retardants in many types of consumer products such as electrical equipment, plastics, and building materials. PBDEs are structurally similar to dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). PBDEs are now ubiquitous; they can be found in air, water, fish, birds, marine mammals, and humans, and in many cases, they are increasing over time. In spite of their widespread occurrence in the environment, only limited information is available on the toxicology of PBDEs. Recent studies showed that PBDE exposure caused aberrations in spontaneous behavior and reduced learning and memory in mice these effects are similar to those seen after exposure to DDT or PCBs. However, the mode of action for this group of chemicals remains unclear. Previously, we demonstrated that PCBs, which are known to cause neurotoxic effects, affected intracellular signaling pathways including [{sup 3}H]arachidonic acid ([{sup 3}H]AA) release, calcium homeostasis, and translocation of protein kinase C (PKC). Regarding PBDEs, we have reported that PBDEs altered [{sup 3}H]AA release in neuronal cultures like PCBs. These signaling pathways have been associated with learning and memory, and the development of the nervous system. The objectives of the present study were to test: (a) whether biologically relevant PBDE congeners affected PKC translocation in neuronal cultures in a similar way to those of other organohalogens; (b) compare the potency and efficacy of PBDE congeners with their 14C-accumulation; and (c) understand the structure-activity relationships among PBDE congeners.

  1. Discovery, synthesis, and structure-activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2β1γ1 activators.

    Science.gov (United States)

    Liu, Junhua; Chen, Dakai; Liu, Peng; He, Mengna; Li, Jia; Li, Jingya; Hu, Lihong

    2014-05-22

    Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype α2β1γ1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure-activity relationship study showed that the amine derivatives at the 24-position (groups I-VI) can improve the potency (EC50: 0.7-2.3 μM) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 1.2 and 0.7 μM) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Three-dimensional quantitative structure-activity relationships and docking studies of some structurally diverse flavonoids and design of new aldose reductase inhibitors

    Directory of Open Access Journals (Sweden)

    Utpal Chandra De

    2015-01-01

    Full Text Available Aldose reductase (AR plays an important role in the development of several long-term diabetic complications. Inhibition of AR activities is a strategy for controlling complications arising from chronic diabetes. Several AR inhibitors have been reported in the literature. Flavonoid type compounds are shown to have significant AR inhibition. The objective of this study was to perform a computational work to get an idea about structural insight of flavonoid type compounds for developing as well as for searching new flavonoid based AR inhibitors. The data-set comprising 68 flavones along with their pIC 50 values ranging from 0.44 to 4.59 have been collected from literature. Structure of all the flavonoids were drawn in Chembiodraw Ultra 11.0, converted into corresponding three-dimensional structure, saved as mole file and then imported to maestro project table. Imported ligands were prepared using LigPrep option of maestro 9.6 version. Three-dimensional quantitative structure-activity relationships and docking studies were performed with appropriate options of maestro 9.6 version installed in HP Z820 workstation with CentOS 6.3 (Linux. A model with partial least squares factor 5, standard deviation 0.2482, R 2 = 0.9502 and variance ratio of regression 122 has been found as the best statistical model.

  3. Structure-activity relationship study of Aib-containing amphipathic helical peptide-cyclic RGD conjugates as carriers for siRNA delivery.

    Science.gov (United States)

    Wada, Shun-Ichi; Takesada, Anna; Nagamura, Yurie; Sogabe, Eri; Ohki, Rieko; Hayashi, Junsuke; Urata, Hidehito

    2017-12-15

    The conjugation of Aib-containing amphipathic helical peptide with cyclo(-Arg-Gly-Asp-d-Phe-Cys-) (cRGDfC) at the C-terminus of the helix peptide (PI) has been reported to be useful for constructing a carrier for targeted siRNA delivery into cells. In order to explore structure-activity relationships for the development of potential carriers for siRNA delivery, we synthesized conjugates of Aib-containing amphipathic helical peptide with cRGDfC at the N-terminus (PII) and both the N- and C-termini (PIII) of the helical peptide. Furthermore, to examine the influence of PI helical chain length on siRNA delivery, truncated peptides containing 16 (PIV), 12 (PV), and 8 (PVI) amino acid residues at the N-terminus of the helical chain were synthesized. PII and PIII, as well as PI, could deliver anti-luciferase siRNA into cells to induce the knockdown of luciferase stably expressed in cells. In contrast, all of the truncated peptides were unlikely to transport siRNA into cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Linear and non-linear quantitative structure-activity relationship models on indole substitution patterns as inhibitors of HIV-1 attachment.

    Science.gov (United States)

    Nirouei, Mahyar; Ghasemi, Ghasem; Abdolmaleki, Parviz; Tavakoli, Abdolreza; Shariati, Shahab

    2012-06-01

    The antiviral drugs that inhibit human immunodeficiency virus (HIV) entry to the target cells are already in different phases of clinical trials. They prevent viral entry and have a highly specific mechanism of action with a low toxicity profile. Few QSAR studies have been performed on this group of inhibitors. This study was performed to develop a quantitative structure-activity relationship (QSAR) model of the biological activity of indole glyoxamide derivatives as inhibitors of the interaction between HIV glycoprotein gp120 and host cell CD4 receptors. Forty different indole glyoxamide derivatives were selected as a sample set and geometrically optimized using Gaussian 98W. Different combinations of multiple linear regression (MLR), genetic algorithms (GA) and artificial neural networks (ANN) were then utilized to construct the QSAR models. These models were also utilized to select the most efficient subsets of descriptors in a cross-validation procedure for non-linear log (1/EC50) prediction. The results that were obtained using GA-ANN were compared with MLR-MLR and MLR-ANN models. A high predictive ability was observed for the MLR, MLR-ANN and GA-ANN models, with root mean sum square errors (RMSE) of 0.99, 0.91 and 0.67, respectively (N = 40). In summary, machine learning methods were highly effective in designing QSAR models when compared to statistical method.

  5. Effects of synthetic and naturally occurring flavonoids on Na+, K+-ATPase: Aspects of the structure-activity relationship and action mechanism

    International Nuclear Information System (INIS)

    Hirano, T.; Oka, K.; Akiba, M.

    1989-01-01

    A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na + , K + -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na + , K + -ATPase from dog kidney cortex when present at concentrations from 40-1000 μM. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC 50 at 257-320 μM. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one much-gt 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one > 2-cyclohexyl-6-hydroxy-benzopyran-4-one > 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block [ 3 H] ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na + , K + -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme

  6. Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, Niels; Storgaard, Morten; Møller, Charlotte

    2015-01-01

    Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal...... carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD...... and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate...

  7. Structure-activity relationship studies of 1,7-diheteroarylhepta-1,4,6-trien-3-ones with two different terminal rings in prostate epithelial cell models.

    Science.gov (United States)

    Wang, Rubing; Zhang, Xiaojie; Chen, Chengsheng; Chen, Guanglin; Sarabia, Cristian; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong

    2017-06-16

    To systematically investigate the structure-activity relationships of 1,7-diheteroarylhepta-1,4,6-trien-3-ones in three human prostate cancer cell models and one human prostate non-neoplastic epithelial cell model, thirty five 1,7-diarylhepta-1,4,6-trien-3-ones with different terminal heteroaromatic rings have been designed for evaluation of their anti-proliferative potency in vitro. These target compounds have been successfully synthesized through two sequential Horner-Wadsworth-Emmons reactions starting from the appropriate aldehydes and tetraethyl (2-oxopropane-1,3-diyl)bis(phosphonate). Their anti-proliferative potency against PC-3, DU-145 and LNCaP human prostate cancer cell lines can be significantly enhanced by the manipulation of the terminal heteroaromatic rings, further demonstrating the utility of 1,7-diarylhepta-1,4,6-trien-3-one as a potential scaffold for the development of anti-prostate cancer agents. The optimal analog 40 is 82-, 67-, and 39-fold more potent than curcumin toward the three prostate cancer cell lines, respectively. The experimental data also reveal that the trienones with two different terminal aromatic rings possess greater potency toward three prostate cancer cell lines, but also have greater capability of suppressing the proliferation of PWR-1E benign human prostate epithelial cells, as compared to the corresponding counterparts with two identical terminal rings and curcumin. The terminal aromatic rings also affect the cell apoptosis perturbation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Quantitative Structure-Activity Relationships Predicting the Antioxidant Potency of 17β-Estradiol-Related Polycyclic Phenols to Inhibit Lipid Peroxidation

    Directory of Open Access Journals (Sweden)

    Katalin Prokai-Tatrai

    2013-01-01

    Full Text Available The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order to relate their molecular structure and properties with their capacity to inhibit lipid peroxidation, a marker of oxidative stress, quantitative structure-activity relationship (QSAR studies were conducted. The inhibition of Fe3+-induced lipid peroxidation in rat brain homogenate, measured through an assay detecting thiobarbituric acid reactive substances for about seventy compounds were correlated with various molecular descriptors. We found that lipophilicity (modeled by the logarithm of the n-octanol/water partition coefficient, logP was the property that influenced most profoundly the potency of these compounds to inhibit lipid peroxidation in the biological medium studied. Additionally, the important contribution of the bond dissociation enthalpy of the phenolic O-H group, a shape index, the solvent-accessible surface area and the energy required to remove an electron from the highest occupied molecular orbital were also confirmed. Several QSAR equations were validated as potentially useful exploratory tools for identifying or designing novel phenolic antioxidants incorporating the structural backbone of 17β-estradiol to assist therapy development against oxidative stress-associated neurodegeneration.

  9. Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability

    Directory of Open Access Journals (Sweden)

    Chen-Peng Chen

    2018-04-01

    Full Text Available The skin permeability (Kp defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical’s skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone.

  10. Structure-activity relationships of dimethylsphingosine (DMS) derivatives and their effects on intracellular pH and Ca2+ in the U937 monocyte cell line.

    Science.gov (United States)

    Chang, Young-Ja; Lee, Yun-Kyung; Lee, Eun-Hee; Park, Jeong-Ju; Chung, Sung-Kee; Im, Dong-Soon

    2006-08-01

    We recently reported that dimethylsphingosine (DMS), a metabolite of sphingolipids, increased intracellular pH and Ca2+ concentration in U937 human monocytes. In the present study, we found that dimethylphytosphingosine (DMPH) induced the above responses more robustly than DMS. However, phytosphingosine, monomethylphytosphingosine or trimethylsphingosine showed little or no activity. Synthetic C3 deoxy analogues of sphingosine did show similar activities, with the C16 analogue more so than C18. The following structure-activity relationships were observed between DMS derivatives and the intracellular pH and Ca2+ concentrations in U937 monocytes; 1) dimethyl modification is important for the DMS-induced increase of intracellular pH and Ca2+, 2) the addition of an OH group on C4 enhances both activities, 3) the deletion of the OH group on C3 has a negligible effect on the activities, and 4) C16 appears to be more effective than C18. We also found that W-7, a calmodulin inhibitor, blocked the DMS-induced pH increase, whereas, KN-62, ML9, and MMPX, specific inhibitors for calmodulin-dependent kinase II, myosin light chain kinase, and Ca(2+)-calmodulin-dependent phosphodiesterase, respectively, did not affect DMS-induced increases of pH in the U937 monocytes.

  11. Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid.

    Science.gov (United States)

    Martínez-Gualda, Belén; Sun, Liang; Rivero-Buceta, Eva; Flores, Aida; Quesada, Ernesto; Balzarini, Jan; Noppen, Sam; Liekens, Sandra; Schols, Dominique; Neyts, Johan; Leyssen, Pieter; Mirabelli, Carmen; Camarasa, María-José; San-Félix, Ana

    2017-03-01

    We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a "decarboxylated" analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Biochemical interpretation of quantitative structure-activity relationships (QSAR) for biodegradation of N-heterocycles: a complementary approach to predict biodegradability.

    Science.gov (United States)

    Philipp, Bodo; Hoff, Malte; Germa, Florence; Schink, Bernhard; Beimborn, Dieter; Mersch-Sundermann, Volker

    2007-02-15

    Prediction of the biodegradability of organic compounds is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. We combined quantitative structure-activity relationships (QSAR) with the systematic collection of biochemical knowledge to establish rules for the prediction of aerobic biodegradation of N-heterocycles. Validated biodegradation data of 194 N-heterocyclic compounds were analyzed using the MULTICASE-method which delivered two QSAR models based on 17 activating (OSAR 1) and on 16 inactivating molecular fragments (GSAR 2), which were statistically significantly linked to efficient or poor biodegradability, respectively. The percentages of correct classifications were over 99% for both models, and cross-validation resulted in 67.9% (GSAR 1) and 70.4% (OSAR 2) correct predictions. Biochemical interpretation of the activating and inactivating characteristics of the molecular fragments delivered plausible mechanistic interpretations and enabled us to establish the following biodegradation rules: (1) Target sites for amidohydrolases and for cytochrome P450 monooxygenases enhance biodegradation of nonaromatic N-heterocycles. (2) Target sites for molybdenum hydroxylases enhance biodegradation of aromatic N-heterocycles. (3) Target sites for hydratation by an urocanase-like mechanism enhance biodegradation of imidazoles. Our complementary approach represents a feasible strategy for generating concrete rules for the prediction of biodegradability of organic compounds.

  13. ICI 56,780 Optimization: Structure-Activity Relationship Studies of 7-(2-Phenoxyethoxy)-4(1H)-quinolones with Antimalarial Activity.

    Science.gov (United States)

    Maignan, Jordany R; Lichorowic, Cynthia L; Giarrusso, James; Blake, Lynn D; Casandra, Debora; Mutka, Tina S; LaCrue, Alexis N; Burrows, Jeremy N; Willis, Paul A; Kyle, Dennis E; Manetsch, Roman

    2016-07-28

    Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.

  14. Effects of heterocyclic-based head group modifications on the structure-activity relationship of tocopherol-based lipids for non-viral gene delivery.

    Science.gov (United States)

    Gosangi, Mallikarjun; Mujahid, Thasneem Yoosuf; Gopal, Vijaya; Patri, Srilakshmi V

    2016-07-12

    Gene therapy, a promising strategy for the delivery of therapeutic nucleic acids, is greatly dependent on the development of efficient vectors. In this study, we designed and synthesized several tocopherol-based lipids varying in the head group region. Here, we present the structure-activity relationship of stable aqueous suspensions of lipids that were synthetically prepared and formulated with 1,2-dioleoyl phosphatidyl ethanolamine (DOPE) as the co-lipid. The physicochemical properties such as the hydrodynamic size, zeta potential, stability and morphology of these formulations were investigated. Interaction with plasmid DNA was clearly demonstrated through gel binding and EtBr displacement assays. Further, the transfection potential was examined in mouse neuroblastoma Neuro-2a, hepatocarcinoma HepG2, human embryonic kidney and Chinese hamster ovarian cell lines, all of different origins. Cell-uptake assays with N-methylpiperidinium, N-methylmorpholinium, N-methylimidazolium and N,N-dimethylaminopyridinium head group containing formulations evidently depicted efficient cell uptake as observed by particulate cytoplasmic fluorescence. Trafficking of lipoplexes using an endocytic marker and rhodamine-labeled phospholipid DHPE indicated that the lipoplexes were not sequestered in the lysosomes. Importantly, lipoplexes were non-toxic and mediated good transfection efficiency as analyzed by β-Gal and GFP reporter gene expression assays which established the superior activity of lipids whose structures correlate strongly with the transfection efficiency.

  15. Effects of synthetic and naturally occurring flavonoids on Na sup + , K sup + -ATPase: Aspects of the structure-activity relationship and action mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, T.; Oka, K.; Akiba, M. (Tokyo College of Pharmacy (Japan))

    1989-01-01

    A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na{sup +}, K{sup +} -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na{sup +}, K{sup +} -ATPase from dog kidney cortex when present at concentrations from 40-1000 {mu}M. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC{sub 50} at 257-320 {mu}M. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one {much gt} 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one {gt} 2-cyclohexyl-6-hydroxy-benzopyran-4-one {gt} 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block ({sup 3}H) ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na{sup +}, K{sup +} -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme.

  16. Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin.

    Science.gov (United States)

    Liu, Tao; Ma, Ming; Ge, Hui-Ming; Yang, Chunying; Cleveland, John; Shen, Ben

    2015-11-01

    Leinamycin (LNM, 1) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4'-dideshydroxy-LNM (5) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1; 5 exhibits comparable activity as 1 with the EC50 values between 8.21 and 275 nM. This work reveals new insight into the structure-activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

    Science.gov (United States)

    Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

    2017-02-22

    Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

  18. Structure-Activity Relationships of New Natural Product-Based Diaryloxazoles with Selective Activity against Androgen Receptor-Positive Breast Cancer Cells.

    Science.gov (United States)

    Robles, Andrew J; McCowen, Shelby; Cai, Shengxin; Glassman, Michaels; Ruiz, Francisco; Cichewicz, Robert H; McHardy, Stanton F; Mooberry, Susan L

    2017-11-22

    Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC. Bioassay-guided fractionation identified two oxazole natural products with selective activity against this cell line. Conducted analog synthesis and structure-activity relationship studies provided analogs with more potent and selective activity against two LAR subtype cell line models, culminating in the discovery of compound 30 (CIDD-0067106). Lead compounds discovered have potent and selective antiproliferative activities, and mechanisms of action studies show they inhibit the activity of the mTORC1 pathway.

  19. Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability.

    Science.gov (United States)

    Chen, Chen-Peng; Chen, Chan-Cheng; Huang, Chia-Wen; Chang, Yen-Ching

    2018-04-15

    The skin permeability ( Kp ) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical's skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone.

  20. Spectral SAR Ecotoxicology of Ionic Liquids: The Daphnia magna Case

    International Nuclear Information System (INIS)

    Putz, M.V.; Lacrama, A.M.; Ostafe, V.; Lacrama, A.M.

    2007-01-01

    Aiming to provide a unified theory of ionic liquids eco toxicity, the recent spectral structure activity relationship (S-SAR) algorithm is employed for testing the two additive models of anionic-cationic interaction containing ionic liquid activity: the causal and the endpoint, |0+> and |1+> models, respectively. As a working system, the Daphnia magna eco toxicity was characterized through the formulated and applied spectral chemical-eco biological interaction principles. Specific anionic-cationic-ionic-liquid rules of interaction along the developed mechanistic hypersurface map of the main eco toxicity paths together with the so-called resonance limitation of the standard statistical correlation analysis were revealed.

  1. Three-dimensional quantitative structure-activity relationship (3D QSAR) and pharmacophore elucidation of tetrahydropyran derivatives as serotonin and norepinephrine transporter inhibitors

    Science.gov (United States)

    Kharkar, Prashant S.; Reith, Maarten E. A.; Dutta, Aloke K.

    2008-01-01

    Three-dimensional quantitative structure-activity relationship (3D QSAR) using comparative molecular field analysis (CoMFA) was performed on a series of substituted tetrahydropyran (THP) derivatives possessing serotonin (SERT) and norepinephrine (NET) transporter inhibitory activities. The study aimed to rationalize the potency of these inhibitors for SERT and NET as well as the observed selectivity differences for NET over SERT. The dataset consisted of 29 molecules, of which 23 molecules were used as the training set for deriving CoMFA models for SERT and NET uptake inhibitory activities. Superimpositions were performed using atom-based fitting and 3-point pharmacophore-based alignment. Two charge calculation methods, Gasteiger-Hückel and semiempirical PM3, were tried. Both alignment methods were analyzed in terms of their predictive abilities and produced comparable results with high internal and external predictivities. The models obtained using the 3-point pharmacophore-based alignment outperformed the models with atom-based fitting in terms of relevant statistics and interpretability of the generated contour maps. Steric fields dominated electrostatic fields in terms of contribution. The selectivity analysis (NET over SERT), though yielded models with good internal predictivity, showed very poor external test set predictions. The analysis was repeated with 24 molecules after systematically excluding so-called outliers (5 out of 29) from the model derivation process. The resulting CoMFA model using the atom-based fitting exhibited good statistics and was able to explain most of the selectivity (NET over SERT)-discriminating factors. The presence of -OH substituent on the THP ring was found to be one of the most important factors governing the NET selectivity over SERT. Thus, a 4-point NET-selective pharmacophore, after introducing this newly found H-bond donor/acceptor feature in addition to the initial 3-point pharmacophore, was proposed.

  2. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size : Structure-activity relationships of non-digestible oligosaccharides.

    Science.gov (United States)

    Akbari, Peyman; Fink-Gremmels, Johanna; Willems, Rianne H A M; Difilippo, Elisabetta; Schols, Henk A; Schoterman, Margriet H C; Garssen, Johan; Braber, Saskia

    2017-08-01

    The direct effects of galacto-oligosaccharides (GOS), including Vivinal ® GOS syrup (VGOS) and purified Vivinal ® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure-activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin. Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA. In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release. This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

  3. Dopamine D(3) receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans.

    Science.gov (United States)

    Haadsma-Svensson, S R; Cleek, K A; Dinh, D M; Duncan, J N; Haber, C L; Huff, R M; Lajiness, M E; Nichols, N F; Smith, M W; Svensson, K A; Zaya, M J; Carlsson, A; Lin, C H

    2001-12-20

    5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D(3) receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D(3) antagonists. Thus, combinations of various alkyl groups were generally inactive at the D(3) receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D(3) binding affinity, the D(2) affinity is also enhanced, resulting in a less than 4-fold preference for the D(3) receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D(3) antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH(3).Me(2)S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et(3)SiH to give the desired product 3 in good overall yield of ( approximately 65%) from the indanone 5c.

  4. Toxicity Assessment of Atrazine and Related Triazine Compounds in the Microtox Assay, and Computational Modeling for Their Structure-Activity Relationship

    Directory of Open Access Journals (Sweden)

    Jerzy Leszczynski

    2000-10-01

    Full Text Available The triazines are a group of chemically similar herbicides including atrazine, cyanazine, and propazine, primarily used to control broadleaf weeds. About 64 to 80 million lbs of atrazine alone are used each year in the United States, making it one of the two most widely used pesticides in the country. All triazines are somewhat persistent in water and mobile in soil. They are among the most frequently detected pesticides in groundwater. They are considered as possible human carcinogens (Group C based on an increase in mammary gland tumors in female laboratory animals. In this research, we performed the Microtox Assay to investigate the acute toxicity of a significant number of triazines including atrazine, atraton, ametryne, bladex, prometryne, and propazine, and some of their degradation products including atrazine desethyl, atrazine deisopropyl, and didealkyled triazine. Tests were carried out as described by Azur Environmental [1]. The procedure measured the relative acute toxicity of triazines, producing data for the calculation of triazine concentrations effecting 50% reduction in bioluminescence (EC50s. Quantitative structure-activity relationships (QSAR were examined based on the molecular properties obtained from quantum mechanical predictions performed for each compound. Toxicity tests yielded EC50 values of 39.87, 273.20, 226.80, 36.96, 81.86, 82.68, 12.74, 11.80, and 78.50 mg/L for atrazine, propazine, prometryne, atraton, atrazine desethyl, atrazine deisopropyl, didealkylated triazine, ametryne, and bladex, respectively; indicating that ametryne was the most toxic chemical while propazine was the least toxic. QSAR evaluation resulted in a coefficient of determination (r2 of 0.86, indicating a good value of toxicity prediction based on the chemical structures/properties of tested triazines.

  5. Structure-activity relationships for flavone interactions with amyloid β reveal a novel anti-aggregatory and neuroprotective effect of 2',3',4'-trihydroxyflavone (2-D08).

    Science.gov (United States)

    Marsh, Dylan T; Das, Sukanya; Ridell, Jessica; Smid, Scott D

    2017-07-15

    Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid β (Aβ). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aβ protein. In the present study we have characterised the Aβ binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Quercetin, transilitin, jaceosidin, nobiletin and 2-D08 were incubated with human Aβ 1-42 for 48h in vitro and effects on Aβ fibrillisation kinetics and morphology measured using Thioflavin T (ThT) and electron microscopy respectively, in addition to effects on neuronal PC12 cell viability. Of the flavones studied, only quercetin, transilitin and 2-D08 significantly inhibited Aβ 1-42 aggregation and toxicity in PC12 cells. Of those, 2-D08 was the most effective inhibitor. The strong anti-amyloid activity of 2-D08 indicates that extensive hydroxylation in the B ring is the most important determinant of activity against β amyloid within the flavone scaffold. The lack of efficacy of jaceosidin and nobiletin indicate that extension of B ring hydroxylation with methoxyl groups result in an incremental loss of anti-fibrillar and neuroprotective activity, highlighting the constraint to vicinal hydroxyl groups in the B ring for effective inhibition of aggregation. These findings reveal further structural insights into anti-amyloid bioactivity of flavonoids in addition to a novel and efficacious anti-aggregatory and neuroprotective effect of the semi-synthetic flavone and sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Such modified flavones may facilitate drug development targeting multiple pathways in neurodegenerative disease. Crown Copyright © 2017

  6. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    Science.gov (United States)

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. An orientation sensitive approach in biomolecule interaction quantitative structure-activity relationship modeling and its application in ion-exchange chromatography.

    Science.gov (United States)

    Kittelmann, Jörg; Lang, Katharina M H; Ottens, Marcel; Hubbuch, Jürgen

    2017-01-27

    Quantitative structure-activity relationship (QSAR) modeling for prediction of biomolecule parameters has become an established technique in chromatographic purification process design. Unfortunately available descriptor sets fail to describe the orientation of biomolecules and the effects of ionic strength in the mobile phase on the interaction with the stationary phase. The literature describes several special descriptors used for chromatographic retention modeling, all of these do not describe the screening of electrostatic potential by the mobile phase in use. In this work we introduce two new approaches of descriptor calculations, namely surface patches and plane projection, which capture an oriented binding to charged surfaces and steric hindrance of the interaction with chromatographic ligands with regard to electrostatic potential screening by mobile phase ions. We present the use of the developed descriptor sets for predictive modeling of Langmuir isotherms for proteins at different pH values between pH 5 and 10 and varying ionic strength in the range of 10-100mM. The resulting model has a high correlation of calculated descriptors and experimental results, with a coefficient of determination of 0.82 and a predictive coefficient of determination of 0.92 for unknown molecular structures and conditions. The agreement of calculated molecular interaction orientations with both, experimental results as well as molecular dynamic simulations from literature is shown. The developed descriptors provide the means for improved QSAR models of chromatographic processes, as they reflect the complex interactions of biomolecules with chromatographic phases. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

    Science.gov (United States)

    Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

    2016-09-01

    We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1-10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633-0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926-0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.

  9. Synthesis, in-vitro cytotoxicity of 1H-benzo[f]chromene derivatives and structure-activity relationships of the 1-aryl group and 9-position.

    Science.gov (United States)

    Mohamed, Hany M; Fouda, Ahmed M; Khattab, Essam S A E H; Agrody, Ahmed M El-; Afifi, Tarek H

    2017-05-01

    A series of 1H-benzo[f]chromene-2-carbonitriles was synthesized and evaluated for their cytotoxic activities against MCF-7, HCT-116, and HepG-2 cancer cells. The SAR studies reported that the substitution in the phenyl ring at 1-position of 1H-benzo[f]chromene nucleus with the specific group, H atom, or methoxy group at 9-position increases the ability of the molecule against the different cell lines.

  10. Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

    Science.gov (United States)

    Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

    2018-03-28

    In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (casein presents an excellent source to produce ACE inhibitory peptides.

  11. Comparative pharmacodynamic analysis of imidazoline compounds using rat model of ocular mydriasis with a test of quantitative structure-activity relationships.

    Science.gov (United States)

    Raczak-Gutknecht, Joanna; Nasal, Antoni; Frąckowiak, Teresa; Kornicka, Anita; Sączewski, Franciszek; Wawrzyniak, Renata; Kubik, Łukasz; Kaliszan, Roman

    2017-09-10

    Imidazol(in)e derivatives, having the chemical structure similar to clonidine, exert diverse pharmacological activities connected with their interactions with alpha2-adrenergic receptors, e.g. hypotension, bradycardia, sedation as well as antinociceptive, anxiolytic, antiarrhythmic, muscle relaxant and mydriatic effects. The mechanism of pupillary dilation observed after systemic administration of imidazol(in)es to rats, mice and cats depends on the stimulation of postsynaptic alpha2-adrenoceptors within the brain. It was proved that the central nervous system (CNS)-localized I1-imidazoline receptors are not engaged in those effects. It appeared interesting to analyze the CNS-mediated pharmacodynamics of imidazole(in)e agents in terms of their chromatographic and calculation chemistry-derived parameters. In the present study a systematic determination and comparative pharmacometric analysis of mydriatic effects in rats were performed on a series of 20 imidazol(in)e agents, composed of the well-known drugs and of the substances used in experimental pharmacology. The eye pupil dilatory activities of the compounds were assessed in anesthetized Wistar rats according to the established Koss method. Among twenty imidazol(in)e derivatives studied, 18 produced diverse dose-dependent mydriatic effects. In the quantitative structure-activity relationships (QSAR) analysis, the pharmacological data (half maximum mydriatic effect - ED 50 in μmol/kg) were considered along with the structural parameters of the agents from molecular modeling. The theoretically calculated lipophilicity parameters, CLOGP, of imidazol(in)es, as well as their lipophilicity parameters from HPLC, logk w , were also considered. The attempts to derive statistically significant QSAR equations for a full series of the agents under study were unsuccessful. However, for a subgroup of eight apparently structurally related imidazol(in)es a significant relationship between log(1/ED 50 ) and logk w values was

  12. Effect of green tea catechins and hydrolyzable tannins on benzo[a]pyrene-induced DNA adducts and structure-activity relationship.

    Science.gov (United States)

    Cao, Pengxiao; Cai, Jian; Gupta, Ramesh C

    2010-04-19

    Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible structure-activity relationship. BP (1 microM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1-200 microM) or vehicle. The purified DNA was analyzed by (32)P-postlabeling. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC(50) = 16 microM) > epicatechin gallate (24 microM) > epigallocatechin (146 microM) > epicatechin (462 microM), suggesting a correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies. Tannic acid (IC(50) = 4 microM) and pentagalloglucose (IC(50) = 26 microM) elicited as much DNA adduct inhibitory activity as the catechins or higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of these compounds was due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP, DNA was incubated with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) (0.5 microM) in the presence of test compounds (200 microM) or vehicle. Significant inhibition of DNA adduct formation was found (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by analysis of the reaction products of anti-BPDE with the catechins and pentagalloglucose by electrospray ionization mass spectrometry and liquid chromatography-mass spectrometry. In conclusion, our data demonstrate that green tea catechins and the hydrolyzable tannins are highly effective in inhibiting BP-DNA adduct formation at least, in part, due to direct interaction of adjacent hydroxyl groups in their structures and that the activity is

  13. Optimization of triazine nitriles as rhodesain inhibitors: structure-activity relationships, bioisosteric imidazopyridine nitriles, and X-ray crystal structure analysis with human cathepsin L.

    Science.gov (United States)

    Ehmke, Veronika; Winkler, Edwin; Banner, David W; Haap, Wolfgang; Schweizer, W Bernd; Rottmann, Matthias; Kaiser, Marcel; Freymond, Céline; Schirmeister, Tanja; Diederich, François

    2013-06-01

    The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 substituent led to high-affinity ligands with inhibition constants down to 2 nM for compounds bearing cyclohexyl substituents. Systematic investigations on the S3 pocket revealed its potential to achieve high activities with aromatic vectors that undergo stacking interactions with the planar peptide backbone forming part of the pocket. X-ray crystal structure analysis with the structurally related enzyme human cathepsin L confirmed the binding mode of the triazine ligand series as proposed by molecular modeling. Sub-micromolar inhibition of the proliferation of cultured parasites was achieved for ligands decorated with the best substituents identified through the optimization cycles. In cell-based assays, the introduction of a basic side chain on the inhibitors resulted in a 35-fold increase in antitrypanosomal activity. Finally, bioisosteric imidazopyridine nitriles were studied in order to prevent off-target effects with unselective nucleophiles by decreasing the inherent electrophilicity of the triazine nitrile headgroup. Using this ligand, the stabilization by intramolecular hydrogen bonding of the thioimidate intermediate, formed upon attack of the catalytic cysteine residue, compensates for the lower reactivity of the headgroup. The imidazopyridine nitrile ligand showed

  14. 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile.

    Science.gov (United States)

    Nawrozkij, Maxim B; Rotili, Dante; Tarantino, Domenico; Botta, Giorgia; Eremiychuk, Alexandre S; Musmuca, Ira; Ragno, Rino; Samuele, Alberta; Zanoli, Samantha; Armand-Ugón, Mercedes; Clotet-Codina, Imma; Novakov, Ivan A; Orlinson, Boris S; Maga, Giovanni; Esté, José A; Artico, Marino; Mai, Antonello

    2008-08-14

    A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl- S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  15. Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: histidine substitution.

    Science.gov (United States)

    Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Rowan, Karen; Yeon, Mitch; Franco, Lucia; Chu, Xin-Jie; Chen, Li; Yagaloff, Keith

    2003-01-06

    Systematic substitution of His(6) residue using non-selective hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)) as the template led to the identification of Bu-Atc(6)(2-aminotetraline-2-carboxylic acid)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which showed moderate selectivity towards hMC4R over hMC1R. Further SAR studies resulted in the discovery of Penta-5-BrAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and Penta-5-Me(2)NAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) which are potent hMC4R agonists and are inactive in hMC1R, hMC3R and hMC5R agonist assays.

  16. Inhibitors of HIV-1 maturation: Development of structure-activity relationship for C-28 amides based on C-3 benzoic acid-modified triterpenoids.

    Science.gov (United States)

    Swidorski, Jacob J; Liu, Zheng; Sit, Sing-Yuen; Chen, Jie; Chen, Yan; Sin, Ny; Venables, Brian L; Parker, Dawn D; Nowicka-Sans, Beata; Terry, Brian J; Protack, Tricia; Rahematpura, Sandhya; Hanumegowda, Umesh; Jenkins, Susan; Krystal, Mark; Dicker, Ira B; Meanwell, Nicholas A; Regueiro-Ren, Alicia

    2016-04-15

    We have recently reported on the discovery of a C-3 benzoic acid (1) as a suitable replacement for the dimethyl succinate side chain of bevirimat (2), an HIV-1 maturation inhibitor that reached Phase II clinical trials before being discontinued. Recent SAR studies aimed at improving the antiviral properties of 2 have shown that the benzoic acid moiety conferred topographical constraint to the pharmacophore and was associated with a lower shift in potency in the presence of human serum albumin. In this manuscript, we describe efforts to improve the polymorphic coverage of the C-3 benzoic acid chemotype through modifications at the C-28 position of the triterpenoid core. The dimethylaminoethyl amides 17 and 23 delivered improved potency toward bevirimat-resistant viruses while increasing C24 in rat oral PK studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Investigating the Relationship between X-Band SAR Data from COSMO-SkyMed Satellite and NDVI for LAI Detection

    Directory of Open Access Journals (Sweden)

    Antonino Maltese

    2013-03-01

    Full Text Available Monitoring spatial and temporal variability of vegetation is important to manage land and water resources, with significant impact on the sustainability of modern agriculture. Cloud cover noticeably reduces the temporal resolution of retrievals based on optical data. COSMO-SkyMed (the new Italian Synthetic Aperture RADAR-SAR opened new opportunities to develop agro-hydrological applications. Indeed, it represents a valuable source of data for operational use, due to the high spatial and temporal resolutions. Although X-band is not the most suitable to model agricultural and hydrological processes, an assessment of vegetation development can be achieved combing optical vegetation indices (VIs and SAR backscattering data. In this paper, a correlation analysis has been performed between the crossed horizontal-vertical (HV backscattering (s°HV and optical VIs (VIopt on several plots. The correlation analysis was based on incidence angle, spatial resolution and polarization mode. Results have shown that temporal changes of s°HV (Δs°HV acquired with high angles (off nadir angle; θ > 40° best correlates with variations of VIopt (ΔVI. The correlation between ΔVI and Δs°HV has been shown to be temporally robust. Based on this experimental evidence, a model to infer a VI from s° (VISAR at the time, ti + 1, once known, the VIopt at a reference time, ti, and Δs°HV between times, ti + 1 and ti, was implemented and verified. This approach has led to the development and validation of an algorithm for coupling a VIopt derived from DEIMOS-1 images and s°HV. The study was carried out over the Sele plain (Campania, Italy, which is mainly characterized by herbaceous crops. In situ measurements included leaf area index (LAI, which were collected weekly between August and September 2011 in 25 sites, simultaneously to COSMO-SkyMed (CSK and DEIMOS-1 imaging. Results confirm that VISAR obtained using the combined model is able to increase the feasibility

  18. Induction of Haustorium Development by Sphaeropsidones in Radicles of the Parasitic Weeds Striga and Orobanche. A Structure-Activity Relationship Study.

    Science.gov (United States)

    Fernández-Aparicio, Mónica; Masi, Marco; Maddau, Lucia; Cimmino, Alessio; Evidente, Marco; Rubiales, Diego; Evidente, Antonio

    2016-06-29

    Crop attack by parasitic weeds such as Striga and Orobanche occurs through developmental processes triggered by host chemodetection. Seeds of those weed species remain dormant in the soil until germination is triggered by host root exudates. The development of haustorium, a parasitic plant organ that invades the host to withdraw its nutrients, is also initiated in Orobanchaceae by host molecular cues. The induction of haustorium development by exogenous signals has previously been reported for Striga but not for Orobanche species. In this work, we demonstrate that sphaeropsidone and epi-sphaeropsidone, two phytotoxic cyclohexene oxides isolated from the fungus Diplodia cupressi, a causal agent of cypress canker, induce haustorium development in radicles of the parasitic weeds Striga hermonthica, Orobanche crenata, and Orobanche cumana. This is the first report of chemical stimulation of haustorium development in radicles of Orobanche in the absence of host. In addition, SAR studies were carried out by testing the haustorium-inducing activity of the natural cyclohexene oxides, seven already known and four new hemisynthetic derivatives, in O. cumana, O. crenata, and S. hermonthica, to find a molecular specificity model required for haustorium induction. The results suggested that the haustorium-inducing activity is due to the possibility to convert the natural sphaeropsidone and natural and hemisynthetic derivatives in the corresponding 3-methoxyquinone and that the stereochemistry at C-5 also seems to affect this activity.

  19. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...

  20. Structure-activity relationships of bumetanide derivatives: correlation between diuretic activity in dogs and inhibition of the human NKCC2A transporter.

    Science.gov (United States)

    Lykke, Kasper; Töllner, Kathrin; Römermann, Kerstin; Feit, Peter W; Erker, Thomas; MacAulay, Nanna; Löscher, Wolfgang

    2015-06-23

    The N-K-Cl cotransporters (NKCCs) mediate the coupled, electroneutral movement of Na + , K + and Cl - ions across cell membranes. There are two isoforms of this cation co-transporter, NKCC1 and NKCC2. NKCC2 is expressed primarily in the kidney and is the target of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. In this study, the effect of a series of diuretically active bumetanide derivatives was investigated on human NKCC2 variant A (hNKCC2A) expressed in Xenopus laevis oocytes. Bumetanide blocked hNKCC2A transport with an IC 50 of 4 μM. There was good correlation between the diuretic potency of bumetanide and its derivatives in dogs and their inhibition of hNKCC2A (r 2 = 0.817; P human NKCC2 splice variants, and may lead to the discovery of novel high-ceiling diuretics. © 2015 The British Pharmacological Society.

  1. Hydrogen Production by Ethanol Steam Reforming (ESR over CeO2 Supported Transition Metal (Fe, Co, Ni, Cu Catalysts: Insight into the Structure-Activity Relationship

    Directory of Open Access Journals (Sweden)

    Michalis Konsolakis

    2016-03-01

    Full Text Available The aim of the present work was to investigate steam reforming of ethanol with regard to H2 production over transition metal catalysts supported on CeO2. Various parameters concerning the effect of temperature (400–800 °C, steam-to-carbon (S/C feed ratio (0.5, 1.5, 3, 6, metal entity (Fe, Co, Ni, Cu and metal loading (15–30 wt.% on the catalytic performance, were thoroughly studied. The optimal performance was obtained for the 20 wt.% Co/CeO2 catalyst, achieving a H2 yield of up to 66% at 400 °C. In addition, the Co/CeO2 catalyst demonstrated excellent stability performance in the whole examined temperature range of 400–800 °C. In contrast, a notable stability degradation, especially at low temperatures, was observed for Ni-, Cu-, and Fe-based catalysts, ascribed mainly to carbon deposition. An extensive characterization study, involving N2 adsorption-desorption (BET, X-ray diffraction (XRD, Scanning Electron Microscopy (SEM/EDS, X-ray Photoelectron Spectroscopy (XPS, and Temperature Programmed Reduction (H2-TPR was undertaken to gain insight into the structure-activity correlation. The excellent reforming performance of Co/CeO2 catalysts could be attributed to their intrinsic reactivity towards ethanol reforming in combination to their high surface oxygen concentration, which hinders the deposition of carbonaceous species.

  2. Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

    Directory of Open Access Journals (Sweden)

    Victoria S Paulsen

    Full Text Available Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2 terminus of the peptide and the fragment arasin 1(1-23 was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23 were shown to be non-toxic to human red blood cells and arasin 1(1-23 was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23 was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC, arasin 1(1-23 was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23 has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23 involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

  3. Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives

    Directory of Open Access Journals (Sweden)

    Asunción Burguete

    2008-12-01

    Full Text Available A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E-3-(3,4,5-trimethoxy-phenyl-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

  4. Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.

    Science.gov (United States)

    Pang, Siu-Kwong

    2017-03-30

    Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Imidazole derivatives as angiotensin II AT1 receptor blockers: Benchmarks, drug-like calculations and quantitative structure-activity relationships modeling

    Science.gov (United States)

    Alloui, Mebarka; Belaidi, Salah; Othmani, Hasna; Jaidane, Nejm-Eddine; Hochlaf, Majdi

    2018-03-01

    We performed benchmark studies on the molecular geometry, electron properties and vibrational analysis of imidazole using semi-empirical, density functional theory and post Hartree-Fock methods. These studies validated the use of AM1 for the treatment of larger systems. Then, we treated the structural, physical and chemical relationships for a series of imidazole derivatives acting as angiotensin II AT1 receptor blockers using AM1. QSAR studies were done for these imidazole derivatives using a combination of various physicochemical descriptors. A multiple linear regression procedure was used to design the relationships between molecular descriptor and the activity of imidazole derivatives. Results validate the derived QSAR model.

  6. Structure-Activity Relationships Based on 3D-QSAR CoMFA/CoMSIA and Design of Aryloxypropanol-Amine Agonists with Selectivity for the Human β3-Adrenergic Receptor and Anti-Obesity and Anti-Diabetic Profiles

    Directory of Open Access Journals (Sweden)

    Marcos Lorca

    2018-05-01

    Full Text Available The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB, and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR techniques. This is the first combined comparative molecular field analysis (CoMFA and comparative molecular similarity index analysis (CoMSIA study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r2ncv = 0.993 and 0.984 and values of r2test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation (q2, r2, r2m, etc. and a final series of compounds was designed and their biological activity was predicted (best pEC50 = 8.561.

  7. The ‘SAR Matrix’ method and its extensions for applications in medicinal chemistry and chemogenomics [v1; ref status: indexed, http://f1000r.es/3gh

    Directory of Open Access Journals (Sweden)

    Disha Gupta-Ostermann

    2014-05-01

    Full Text Available We describe the ‘Structure-Activity Relationship (SAR Matrix’ (SARM methodology that is based upon a special two-step application of the matched molecular pair (MMP formalism. The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets. It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces. The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

  8. The ‘SAR Matrix’ method and its extensions for applications in medicinal chemistry and chemogenomics [v2; ref status: indexed, http://f1000r.es/3rg

    Directory of Open Access Journals (Sweden)

    Disha Gupta-Ostermann

    2014-06-01

    Full Text Available We describe the ‘Structure-Activity Relationship (SAR Matrix’ (SARM methodology that is based upon a special two-step application of the matched molecular pair (MMP formalism. The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets. It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces. The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

  9. Keynote presentation : SAR systems

    NARCIS (Netherlands)

    Halsema, D. van; Otten, M.P.G.; Maas, A.P.M.; Bolt, R.J.; Anitori, L.

    2011-01-01

    Synthetic Aperture Radar (SAR) systems are becoming increasingly important sensors in as well the military environment as in the civilian market. In this keynote presentation an overview will be given over more than 2 decades of SAR system∼ and SAR application development at TNO in the Netherlands.

  10. MS/MS fragmentation-guided search of TMG-chitooligomycins and their structure-activity relationship in specific β-N-acetylglucosaminidase inhibition.

    Science.gov (United States)

    Usuki, Hirokazu; Yamamoto, Yukihiro; Kumagai, Yuya; Nitoda, Teruhiko; Kanzaki, Hiroshi; Hatanaka, Tadashi

    2011-04-21

    The reducing tetrasaccharide TMG-chitotriomycin (1) is an inhibitor of β-N-acetylglucosaminidase (GlcNAcase), produced by the actinomycete Streptomyces anulatus NBRC13369. The inhibitor shows a unique inhibitory spectrum, that is, selectivity toward enzymes from chitin-containing organisms such as insects and fungi. Nevertheless, its structure-selectivity relationship remains to be clarified. In this study, we conducted a structure-guided search of analogues of 1 in order to obtain diverse N,N,N-trimethylglucosaminium (TMG)-containing chitooligosaccharides. In this approach, the specific fragmentation profile of 1 on ESI-MS/MS analysis was used for the selective detection of desired compounds. As a result, two new analogues, named TMG-chitomonomycin (3) and TMG-chitobiomycin (2), were obtained from a culture filtrate of 1-producing Streptomyces. Their enzyme-inhibiting activity revealed that the potency and selectivity depended on the degree of polymerization of the reducing end GlcNAc units. Furthermore, a computational modeling study inspired the inhibitory mechanism of TMG-related compounds as a mimic of the substrate in the Michaelis complex of the GH20 enzyme. This study is an example of the successful application of a MS/MS experiment for structure-guided isolation of natural products.

  11. Accepting the Invitation to Open Innovation in Malaria Drug Discovery: Synthesis, Biological Evaluation, and Investigation on the Structure-Activity Relationships of Benzo[b]thiophene-2-carboxamides as Antimalarial Agents.

    Science.gov (United States)

    Pieroni, Marco; Azzali, Elisa; Basilico, Nicoletta; Parapini, Silvia; Zolkiewski, Michal; Beato, Claudia; Annunziato, Giannamaria; Bruno, Agostino; Vacondio, Federica; Costantino, Gabriele

    2017-03-09

    Malaria eradication is a global health priority, but current therapies are not always suitable for providing a radical cure. Artemisinin has paved the way for the current malaria treatment, the so-called Artemisinin-based Combination Therapy (ACT). However, with the detection of resistance to ACT, innovative compounds active against multiple parasite species and at multiple life stages are needed. GlaxoSmithKline has recently disclosed the results of a phenotypic screening of an internal library, publishing a collection of 400 antimalarial chemotypes, termed the "Malaria Box". After analysis of the data set, we have carried out a medicinal chemistry campaign in order to define the structure-activity relationships for one of the released compounds, which embodies a benzothiophene-2-carboxamide core. Thirty-five compounds were prepared, and a description of the structural features responsible for the in vitro activity against different strains of P. falciparum, the toxicity, and the metabolic stability is herein reported.

  12. Comparison of 3D quantitative structure-activity relationship methods: Analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis

    Science.gov (United States)

    Woolfrey, John R.; Avery, Mitchell A.; Doweyko, Arthur M.

    1998-03-01

    Two three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL), were compared with respect to the analysis of a training set of 154 artemisinin analogues. Five models were created, including a complete HASL and two trimmed versions, as well as two CoMFA models (leave-one-out standard CoMFA and the guided-region selection protocol). Similar r2 and q2 values were obtained by each method, although some striking differences existed between CoMFA contour maps and the HASL output. Each of the four predictive models exhibited a similar ability to predict the activity of a test set of 23 artemisinin analogues, although some differences were noted as to which compounds were described well by either model.

  13. Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety.

    Science.gov (United States)

    Qian, Shan; Shah, Aashay K; Head, Sarah A; Liu, Jun O; Jin, Zhendong

    2016-08-01

    Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2-C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4-C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Validity and validation of expert (Q)SAR systems.

    Science.gov (United States)

    Hulzebos, E; Sijm, D; Traas, T; Posthumus, R; Maslankiewicz, L

    2005-08-01

    At a recent workshop in Setubal (Portugal) principles were drafted to assess the suitability of (quantitative) structure-activity relationships ((Q)SARs) for assessing the hazards and risks of chemicals. In the present study we applied some of the Setubal principles to test the validity of three (Q)SAR expert systems and validate the results. These principles include a mechanistic basis, the availability of a training set and validation. ECOSAR, BIOWIN and DEREK for Windows have a mechanistic or empirical basis. ECOSAR has a training set for each QSAR. For half of the structural fragments the number of chemicals in the training set is >4. Based on structural fragments and log Kow, ECOSAR uses linear regression to predict ecotoxicity. Validating ECOSAR for three 'valid' classes results in predictivity of > or = 64%. BIOWIN uses (non-)linear regressions to predict the probability of biodegradability based on fragments and molecular weight. It has a large training set and predicts non-ready biodegradability well. DEREK for Windows predictions are supported by a mechanistic rationale and literature references. The structural alerts in this program have been developed with a training set of positive and negative toxicity data. However, to support the prediction only a limited number of chemicals in the training set is presented to the user. DEREK for Windows predicts effects by 'if-then' reasoning. The program predicts best for mutagenicity and carcinogenicity. Each structural fragment in ECOSAR and DEREK for Windows needs to be evaluated and validated separately.

  15. Improving the applicability of (Q)SARs for percutaneous penetration in regulatory risk assessment.

    Science.gov (United States)

    Bouwman, T; Cronin, M T D; Bessems, J G M; van de Sandt, J J M

    2008-04-01

    The new regulatory framework REACH (Registration, Evaluation, and Authorisation of Chemicals) foresees the use of non-testing approaches, such as read-across, chemical categories, structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs). Although information on skin absorption data are not a formal requirement under REACH, data on dermal absorption are an integral part of risk assessment of substances/products to which man is predominantly exposed via the dermal route. In this study, we assess the present applicability of publicly available QSARs on skin absorption for risk assessment purposes. We explicitly did not aim to give scientific judgments on individual QSARs. A total of 33 QSARs selected from the public domain were evaluated using the OECD (Organisation for Economic Co-operation and Development) Principles for the Validation of (Q)SAR Models. Additionally, several pragmatic criteria were formulated to select QSARs that are most suitable for their use in regulatory risk assessment. Based on these criteria, four QSARs were selected. The predictivity of these QSARs was evaluated by comparing their outcomes with experimentally derived skin absorption data (for 62 compounds). The predictivity was low for three of four QSARs, whereas one model gave reasonable predictions. Several suggestions are made to increase the applicability of QSARs for skin absorption for risk assessment purposes.

  16. Structure Activity Relationship of Brevenal Hydrazide Derivatives

    Directory of Open Access Journals (Sweden)

    Allan Goodman

    2014-03-01

    Full Text Available Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and bronchoconstriction. Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial attributes when administered alone. For example, in an asthmatic sheep model, brevenal has been shown to increase tracheal mucosal velocity, an attribute which has led to its development as a potential treatment for Cystic Fibrosis. The mechanism of action of brevenal is poorly understood and the exact binding site has not been elucidated. In an attempt to further understand the mechanism of action of brevenal and potentially develop a second generation drug candidate, a series of brevenal derivatives were prepared through modification of the aldehyde moiety. These derivatives include aliphatic, aromatic and heteroaromatic hydrazide derivatives. The brevenal derivatives were tested using in vitro synaptosome binding assays to determine the ability of the compounds to displace brevetoxin and brevenal from their native receptors. A sheep inhalation model was used to determine if instillation of the brevenal derivatives resulted in bronchoconstriction. Only small modifications were tolerated, with larger moieties leading to loss of affinity for the brevenal receptor and bronchoconstriction in the sheep model.

  17. Inhibition of 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure-Activity Relationship in a Model System.

    Science.gov (United States)

    Yu, Chundi; Shao, Zeping; Liu, Bing; Zhang, Yan; Wang, Shuo

    2016-08-01

    The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure-activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect. © 2016 Institute of Food Technologists®

  18. Severe acute respiratory syndrome (SARS)

    Science.gov (United States)

    SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

  19. Understanding of the structure activity relationship of PtPd bimetallic catalysts prepared by surface organometallic chemistry and ion exchange during the reaction of iso-butane with hydrogen

    KAUST Repository

    Al-Shareef, Reem A.; Harb, Moussab; Saih, Youssef; Ould-Chikh, Samy; Roldan, Manuel A.; Anjum, Dalaver H.; Guyonnet, Elodie Bile; Candy, Jean-Pierre; Jan, Deng-Yang; Abdo, Suheil F.; Aguilar-Tapia, Antonio; Proux, Olivier; Hazemann, Jean-Louis; Basset, Jean-Marie

    2018-01-01

    Well-defined silica supported bimetallic catalysts Pt100-x Pdx were prepared by Surface Organometallic Chemistry (SOMC) and Ionic-Exchange (IE) methods. For all investigated catalysts, iso-butane reaction with hydrogen under differential conditions led to the formation of methane and propane, n-butane, and traces of iso-butylene. The total reaction rate decreased with increasing the Pd loading for both catalysts series as a result of decreasing turnover rate of both isomerization and hydrogenolysis. In the case of Pt100-x Pdx(SOMC) catalysts, the experimental results in combination with DFT calculations suggested a selective coverage of Pt (1 0 0) surface by agglomerated Pd atoms like “islands”, assuming that each metal roughly keeps its intrinsic catalytic properties with relatively small electron transfer from Pt to Pd in the case of Pt-rich sample and from Pd to Pt in the case of Pd-rich sample. For the PtPd catalysts prepared by IE, the catalytic behavior could be explained by the formation of a surface alloy between Pt and Pd in the case of Pd-rich sample and by the segregation of a small amount of Pd on the surface in the case of Pt-rich sample, as demonstrated by TEM, EXAFS and DFT. The catalytic results were explained by a structure activity relationship based on the proposed mechanism of CH bond and CC bond activation and cleavage for iso-butane hydrogenolysis, isomerization, cracking and dehydrogenation.

  20. Understanding of the structure activity relationship of PtPd bimetallic catalysts prepared by surface organometallic chemistry and ion exchange during the reaction of iso-butane with hydrogen

    KAUST Repository

    Alshareef, Reem Abdul aziz Hamed

    2018-04-25

    Well-defined silica supported bimetallic catalysts Pt100-x Pdx were prepared by Surface Organometallic Chemistry (SOMC) and Ionic-Exchange (IE) methods. For all investigated catalysts, iso-butane reaction with hydrogen under differential conditions led to the formation of methane and propane, n-butane, and traces of iso-butylene. The total reaction rate decreased with increasing the Pd loading for both catalysts series as a result of decreasing turnover rate of both isomerization and hydrogenolysis. In the case of Pt100-x Pdx(SOMC) catalysts, the experimental results in combination with DFT calculations suggested a selective coverage of Pt (1 0 0) surface by agglomerated Pd atoms like “islands”, assuming that each metal roughly keeps its intrinsic catalytic properties with relatively small electron transfer from Pt to Pd in the case of Pt-rich sample and from Pd to Pt in the case of Pd-rich sample. For the PtPd catalysts prepared by IE, the catalytic behavior could be explained by the formation of a surface alloy between Pt and Pd in the case of Pd-rich sample and by the segregation of a small amount of Pd on the surface in the case of Pt-rich sample, as demonstrated by TEM, EXAFS and DFT. The catalytic results were explained by a structure activity relationship based on the proposed mechanism of CH bond and CC bond activation and cleavage for iso-butane hydrogenolysis, isomerization, cracking and dehydrogenation.

  1. Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.

    Science.gov (United States)

    Shrestha, Aarajana; Jin Oh, Hye; Kim, Mi Jin; Pun, Nirmala Tilija; Magar, Til Bahadur Thapa; Bist, Ganesh; Choi, Hongseok; Park, Pil-Hoon; Lee, Eung-Seok

    2017-06-16

    As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Kinetic Study of the Aroxyl-Radical-Scavenging Activity of Five Fatty Acid Esters and Six Carotenoids in Toluene Solution: Structure-Activity Relationship for the Hydrogen Abstraction Reaction.

    Science.gov (United States)

    Mukai, Kazuo; Yoshimoto, Maya; Ishikura, Masaharu; Nagaoka, Shin-Ichi

    2017-08-17

    A kinetic study of the reaction between an aroxyl radical (ArO • ) and fatty acid esters (LHs 1-5, ethyl stearate 1, ethyl oleate 2, ethyl linoleate 3, ethyl linolenate 4, and ethyl arachidonate 5) has been undertaken. The second-order rate constants (k s ) for the reaction of ArO • with LHs 1-5 in toluene at 25.0 °C have been determined spectrophotometrically. The k s values obtained increased in the order of LH 1 LHs 1-5. The k s value for LH 5 was 2.93 × 10 -3 M -1 s -1 . From the result, it has been clarified that the reaction of ArO • with LHs 1-5 was explained by an allylic hydrogen abstraction reaction. A similar kinetic study was performed for the reaction of ArO • with six carotenoids (Car-Hs 1-6, astaxanthin 1, β-carotene 2, lycopene 3, capsanthin 4, zeaxanthin 5, and lutein 6). The k s values obtained increased in the order of Car-H 1 LHs 1-5. The results of detailed analyses of the k s values for the above reaction indicated that the reaction was also explained by an allylic hydrogen abstraction reaction. Furthermore, the structure-activity relationship for the reaction was discussed by taking the result of density functional theory calculation reported by Martinez and Barbosa into account.

  3. Influence of lipophilicity in O-acyl and O-alkyl derivatives of juglone and lawsone: a structure-activity relationship study in the search for natural herbicide models.

    Science.gov (United States)

    Durán, Alexandra G; Chinchilla, Nuria; Molinillo, José Mg; Macías, Francisco A

    2018-03-01

    Naphthoquinones are known for their broad range of biological activities. Given the increasing demands of consumers in relation to food quality and growing concerns about the impact of synthetic herbicides, it is necessary to search for new agrochemicals. Natural products and allelopathy provide new alternatives for the development of pesticides with lower toxicity and greater environmental compatibility. A structure-activity relationship to evaluate the effect of bioavailability was performed. A total of 44 O-acyl and O-alkyl derivatives of juglone and lawsone with different linear chain lengths were prepared. These compounds were tested on etiolated wheat coleoptiles, standard target species (STS) and four weeds, Echinochloa crus-galli L., Lolium rigidum Gaud., Lolium perenne L. and Avena fatua L. The results showed a strong influence of lipophilicity and, in most cases, the data fitted a logP-dependent quadratic mathematical model. The effects produced were mostly stunting and necrosis caused by growth inhibition. The potential structure and activity behaviour is described. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara

    2015-10-15

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR\\'s ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  5. Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

    Science.gov (United States)

    Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-07-20

    The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

  6. Identification of new 2,5-diketopiperazine derivatives as simultaneous effective inhibitors of αβ-tubulin and BCRP proteins: Molecular docking, Structure-Activity Relationships and virtual consensus docking studies

    Science.gov (United States)

    Fani, Najmeh; Sattarinezhad, Elham; Bordbar, Abdol-Khalegh

    2017-06-01

    In the first part of this paper, docking method was employed in order to study the binding mechanism of breast cancer resistance protein (BCRP) with a group of previously synthesized TPS-A derivatives which known as potent inhibitors of this protein to get insight into drug binding site of BCRP and to explore structure-activity relationship of these compounds. Molecular docking results showed that most of these compounds bind in the binding site of BCRP at the interface between the membrane and outer environment. In the second part, a group of designed TPS-A derivatives which showed good binding energies in the binding site of αβ-tubulin in the previous study were chosen to study their binding energies in the binding site of BCRP to investigate their simultaneous inhibitory effect on both αβ-tubulin and BCRP. The results showed that all of these compounds bind to the binding site of BCRP with relatively suitable binding energies and therefore could be potential inhibitors of both αβ-tubulin and BCRP proteins. Finally, virtual consensus docking method was utilized with the aim of design of new 2,5-diketopiperazine derivatives with significant inhibitory effect on both αβ-tubulin and BCRP proteins. For this purpose binding energies of a library of 2,5-diketopiperazine derivatives in the binding sites of αβ-tubulin and BCRP was investigated by using AutoDock and AutoDock vina tools. Molecular docking results revealed that a group of 36 compounds among them exhibit strong anti-tubulin and anti-BCRP activity.

  7. Discovery, characterization and structure-activity relationships of an inhibitor of inward rectifier potassium (Kir channels with preference for Kir2.3, Kir3.X and Kir7.1

    Directory of Open Access Journals (Sweden)

    Jerod S Denton

    2011-11-01

    Full Text Available The inward rectifier family of potassium (Kir channels is comprised of at least 16 family members exhibiting broad and often overlapping cellular, tissue or organ distributions. The discovery of disease-causing mutations in humans and experiments on knockout mice has underscored the importance of Kir channels in physiology and in some cases raised questions about their potential as drug targets. However, the paucity of potent and selective small-molecule modulators targeting specific family members has with few exceptions mired efforts to understand their physiology and assess their therapeutic potential. A growing body of evidence suggests that GIRK (G protein-regulated inward rectifier K channels of the Kir3.X subfamily may represent novel targets for the treatment of atrial fibrillation. In an effort to expand the molecular pharmacology of GIRK, we performed a thallium (Tl+ flux-based high-throughput screen (HTS of a Kir1.1 inhibitor library for modulators of GIRK. One compound, termed VU573, exhibited 10-fold selectivity for GIRK over Kir1.1 (IC50 = 1.9 M and 19 M, respectively and was therefore selected for further study. In electrophysiological experiments performed on Xenopus laevis oocytes and mammalian cells, VU573 inhibited Kir3.1/3.2 (neuronal GIRK and Kir3.1/3.4 (cardiac GIRK channels with equal potency and preferentially inhibited GIRK, Kir2.3 and Kir7.1 over Kir1.1 and Kir2.1. Tl+ flux assays were established for Kir2.3 and the M125R pore mutant of Kir7.1 to support medicinal chemistry efforts to develop more potent and selective analogs for these channels. The structure-activity relationships of VU573 revealed few analogs with improved potency, however two compounds retained most of their activity toward GIRK and Kir2.3 and lost activity toward Kir7.1. We anticipate that the VU573 series will be useful for exploring the physiology and structure-function relationships of these Kir channels.

  8. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara; Rockwood, Alyn; Ghanem, Bernard

    2015-01-01

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR's ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  9. Public (Q)SAR Services, Integrated Modeling Environments, and Model Repositories on the Web: State of the Art and Perspectives for Future Development.

    Science.gov (United States)

    Tetko, Igor V; Maran, Uko; Tropsha, Alexander

    2017-03-01

    Thousands of (Quantitative) Structure-Activity Relationships (Q)SAR models have been described in peer-reviewed publications; however, this way of sharing seldom makes models available for the use by the research community outside of the developer's laboratory. Conversely, on-line models allow broad dissemination and application representing the most effective way of sharing the scientific knowledge. Approaches for sharing and providing on-line access to models range from web services created by individual users and laboratories to integrated modeling environments and model repositories. This emerging transition from the descriptive and informative, but "static", and for the most part, non-executable print format to interactive, transparent and functional delivery of "living" models is expected to have a transformative effect on modern experimental research in areas of scientific and regulatory use of (Q)SAR models. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity: in silico bioinformatic step-by-step guide using quantitative structure-activity relationships.

    Science.gov (United States)

    Hattotuwagama, Channa K; Doytchinova, Irini A; Flower, Darren R

    2007-01-01

    Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method

  11. Cardiac glycoside activities link Na(+)/K(+) ATPase ion-transport to breast cancer cell migration via correlative SAR.

    Science.gov (United States)

    Magpusao, Anniefer N; Omolloh, George; Johnson, Joshua; Gascón, José; Peczuh, Mark W; Fenteany, Gabriel

    2015-02-20

    The cardiac glycosides ouabain and digitoxin, established Na(+)/K(+) ATPase inhibitors, were found to inhibit MDA-MB-231 breast cancer cell migration through an unbiased chemical genetics screen for cell motility. The Na(+)/K(+) ATPase acts both as an ion-transporter and as a receptor for cardiac glycosides. To delineate which function is related to breast cancer cell migration, structure-activity relationship (SAR) profiles of cardiac glycosides were established at the cellular (cell migration inhibition), molecular (Na(+)/K(+) ATPase inhibition), and atomic (computational docking) levels. The SAR of cardiac glycosides and their analogs revealed a similar profile, a decrease in potency when the parent cardiac glycoside structure was modified, for each activity investigated. Since assays were done at the cellular, molecular, and atomic levels, correlation of SAR profiles across these multiple assays established links between cellular activity and specific protein-small molecule interactions. The observed antimigratory effects in breast cancer cells are directly related to the inhibition of Na(+)/K(+) transport. Specifically, the orientation of cardiac glycosides at the putative cation permeation path formed by transmembrane helices αM1-M6 correlates with the Na(+) pump activity and cell migration. Other Na(+)/K(+) ATPase inhibitors that are structurally distinct from cardiac glycosides also exhibit antimigratory activity, corroborating the conclusion that the antiport function of Na(+)/K(+) ATPase and not the receptor function is important for supporting the motility of MDA-MB-231 breast cancer cells. Correlative SAR can establish new relationships between specific biochemical functions and higher-level cellular processes, particularly for proteins with multiple functions and small molecules with unknown or various modes of action.

  12. SAR studies directed toward the pyridine moiety of the sap-feeding insecticide sulfoxaflor (Isoclast™ active).

    Science.gov (United States)

    Loso, Michael R; Benko, Zoltan; Buysse, Ann; Johnson, Timothy C; Nugent, Benjamin M; Rogers, Richard B; Sparks, Thomas C; Wang, Nick X; Watson, Gerald B; Zhu, Yuanming

    2016-02-01

    Sap-feeding insect pests constitute a major insect pest complex that includes a range of aphids, whiteflies, planthoppers and other insect species. Sulfoxaflor (Isoclast™ active), a new sulfoximine class insecticide, targets sap-feeding insect pests including those resistant to many other classes of insecticides. A structure activity relationship (SAR) investigation of the sulfoximine insecticides revealed the importance of a 3-pyridyl ring and a methyl substituent on the methylene bridge linking the pyridine and the sulfoximine moiety to achieving strong Myzus persicae activity. A more in depth QSAR investigation of pyridine ring substituents revealed a strong correlation with the calculated logoctanol/water partition coefficient (SlogP). Model development resulted in a highly predictive model for a set of 18 sulfoximines including sulfoxaflor. The model is consistent with and helps explain the highly optimized pyridine substitution pattern for sulfoxaflor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Quantitative relationship between SAR and temperature rise inside eyeball in a realistic human heat model for 1.5 GHz-microwave exposure; 1.5GHz maikuroha wo abita tobu real model ni okeru gankyunai no hikyushuritsu to josho ondo tono teiryo kankei

    Energy Technology Data Exchange (ETDEWEB)

    Takai, K.; Fujiwara, O. [Nagoya Institute of Technology, Nagoya (Japan)

    1997-12-20

    For investigating biological effects of a localized SAR (specific absorption rate) deposited in a human body for electromagnetic wave exposure, it is indispensable to graps a temperature-rise inside a human brain including the control center for the body temperature. This paper numerically analyzes a temperature-rise inside an eyeball of our developed realistic head model for 1.5 GHz microwave exposure, using the FD-TD (finite-difference time-domain) method. The computed results are validated in comparison with the data obtained by Taflove and his colleague. In order to examine a quantitative relationship between the localized SAR and temperature-rise, we also obtained a tissue amount over which the localized SAR should be averaged so as to well reflect the temperature-rise distribution inside the eyeball. 15 refs., 9 figs., 3 tabs.

  14. Crop Classification by Polarimetric SAR

    DEFF Research Database (Denmark)

    Skriver, Henning; Svendsen, Morten Thougaard; Nielsen, Flemming

    1999-01-01

    Polarimetric SAR-data of agricultural fields have been acquired by the Danish polarimetric L- and C-band SAR (EMISAR) during a number of missions at the Danish agricultural test site Foulum during 1995. The data are used to study the classification potential of polarimetric SAR data using...

  15. Bats and SARS

    Centers for Disease Control (CDC) Podcasts

    Bats are a natural reservoir for emerging viruses, among them henipaviruses and rabies virus variants. Dr. Nina Marano, Chief, Geographic Medicine and Health Promotion Branch, Division of Global Migration and Quarantine, CDC, explains connection between horseshoe bats and SARS coronavirus transmission.

  16. Bats and SARS

    Centers for Disease Control (CDC) Podcasts

    2006-11-08

    Bats are a natural reservoir for emerging viruses, among them henipaviruses and rabies virus variants. Dr. Nina Marano, Chief, Geographic Medicine and Health Promotion Branch, Division of Global Migration and Quarantine, CDC, explains connection between horseshoe bats and SARS coronavirus transmission.  Created: 11/8/2006 by Emerging Infectious Diseases.   Date Released: 11/17/2006.

  17. Data Analytics for SAR

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, David Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Calef, Matthew Thomas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-02

    We assess the ability of variants of anomalous change detection (ACD) to identify human activity associated with large outdoor music festivals as they are seen from synthetic aperture radar (SAR) imagery collected by the Sentinel-1 satellite constellation. We found that, with appropriate feature vectors, ACD using random-forest machine learning was most effective at identifying changes associated with the human activity.

  18. Bistatic SAR: Proof of Concept.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Doren, Neall E.; Bacon, Terry A.; Wahl, Daniel E.; Eichel, Paul H.; Jakowatz, Charles V,; Delaplain, Gilbert G.; Dubbert, Dale F.; Tise, Bertice L.; White, Kyle R.

    2014-10-01

    Typical synthetic aperture RADAR (SAR) imaging employs a co-located RADAR transmitter and receiver. Bistatic SAR imaging separates the transmitter and receiver locations. A bistatic SAR configuration allows for the transmitter and receiver(s) to be in a variety of geometric alignments. Sandia National Laboratories (SNL) / New Mexico proposed the deployment of a ground-based RADAR receiver. This RADAR receiver was coupled with the capability of digitizing and recording the signal collected. SNL proposed the possibility of creating an image of targets the illuminating SAR observes. This document describes the developed hardware, software, bistatic SAR configuration, and its deployment to test the concept of a ground-based bistatic SAR. In the proof-of-concept experiments herein, the RADAR transmitter will be a commercial SAR satellite and the RADAR receiver will be deployed at ground level, observing and capturing RADAR ground/targets illuminated by the satellite system.

  19. Combining pharmacophore fingerprints and PLS-discriminant analysis for virtual screening and SAR elucidation

    DEFF Research Database (Denmark)

    Askjær, Sune; Langgård, Morten

    2008-01-01

    The criterion of success for the initial stages of a ligand-based drug-discovery project is dual. First, a set of suitable lead compounds has to be identified. Second, a level of a preliminary structure-activity relationship (SAR) of the identified ligands has to be established in order to guide ...... by the protein-binding site known from X-ray complexes. The result of this analysis assists in explaining the efficiency of 2D pharmacophore fingerprints as descriptors in virtual screening....... the lead optimization toward a final drug candidate. This paper presents a combined approach to solving these two problems of ligand-based virtual screening and elucidation of SAR based on interplay between pharmacophore fingerprints and interpretation of PLS-discriminant analysis (PLS-DA) models....... The virtual screening capability of the PLS-DA method is compared to group fusion maximum similarity searching in a test using four graph-based pharmacophore fingerprints over a range of 10 diverse targets. The PLS-DA method was generally found to do better than the Smax method. The GpiDAPH3 and PCH...

  20. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    Science.gov (United States)

    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Common SAR Derived from Linear and Non-linear QSAR Studies on AChE Inhibitors used in the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Pulikkal, Babitha Pallikkara; Marunnan, Sahila Mohammed; Bandaru, Srinivas; Yadav, Mukesh; Nayarisseri, Anuraj; Sureshkumar, Sivanpillai

    2017-11-14

    Deficits in cholinergic neurotransmission due to the degeneration of cholinergic neurons in the brain are believed to be one of the major causes of the memory impairments associated with AD. Targeting acetyl cholinesterase (AChE) surfaced as a potential therapeutic target in the treatment of Alzheimer's disease. The present study is pursued to develop quantitative structure activity relationship (QSAR) models to determine chemical descriptors responsible for AChE activity. Two different sets of AChE inhibitors, dataset-I (30 compounds) and dataset-II (20 compounds) were investigated through MLR aided linear and SVM aided non-linear QSAR models. The obtained QSAR models were found statistically fit, stable and predictive on validation scales. These QSAR models were further investigated for their common structure-activity relationship in terms of overlapping molecular descriptors selection. Atomic mass weighted 3D Morse descriptors (MATS5m) and Radial Distribution Function (RDF045m) descriptors were found in common SAR for both the datasets. Electronegativity weighted (MATS5e, HATSe, and Mor17e) descriptors have also been identified in regulative roles towards endpoint values of dataset-I and dataset-II. The common SAR identified in these linear and non-linear QSAR models could be utilized to design novel inhibitors of AChE with improved biological activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Bistatic sAR data processing algorithms

    CERN Document Server

    Qiu, Xiaolan; Hu, Donghui

    2013-01-01

    Synthetic Aperture Radar (SAR) is critical for remote sensing. It works day and night, in good weather or bad. Bistatic SAR is a new kind of SAR system, where the transmitter and receiver are placed on two separate platforms. Bistatic SAR is one of the most important trends in SAR development, as the technology renders SAR more flexible and safer when used in military environments. Imaging is one of the most difficult and important aspects of bistatic SAR data processing. Although traditional SAR signal processing is fully developed, bistatic SAR has a more complex system structure, so sign

  3. The experience of SARS-related stigma at Amoy Gardens.

    Science.gov (United States)

    Lee, Sing; Chan, Lydia Y Y; Chau, Annie M Y; Kwok, Kathleen P S; Kleinman, Arthur

    2005-11-01

    Severe Acute Respiratory Syndrome (SARS) possesses characteristics that render it particularly prone to stigmatization. SARS-related stigma, despite its salience for public health and stigma research, has had little examination. This study combines survey and case study methods to examine subjective stigma among residents of Amoy Gardens (AG), the first officially recognized site of community outbreak of SARS in Hong Kong. A total of 903 residents of AG completed a self-report questionnaire derived from two focus groups conducted toward the end of the 3-month outbreak. Case studies of two residents who lived in Block E, the heart of the SARS epidemic at AG, complement the survey data. Findings show that stigma affected most residents and took various forms of being shunned, insulted, marginalized, and rejected in the domains of work, interpersonal relationships, use of services and schooling. Stigma was also associated with psychosomatic distress. Residents' strategies for diminishing stigma varied with gender, age, education, occupation, and proximity to perceived risk factors for SARS such as residential location, previous SARS infection and the presence of ex-SARS household members. Residents attributed stigma to government mismanagement, contagiousness of the mysterious SARS virus, and alarmist media reporting. Stigma clearly decreased, but never completely disappeared, after the outbreak. The findings confirm and add to existing knowledge on the varied origins, correlates, and impacts of stigma. They also highlight the synergistic roles of inconsistent health policy responses and risk miscommunication by the media in rapidly amplifying stigma toward an unfamiliar illness. While recognizing the intrinsically stigmatizing nature of public health measures to control SARS, we recommend that a consistent inter-sectoral approach is needed to minimize stigma and to make an effective health response to future outbreaks.

  4. Follow-up: Prospective compound design using the ‘SAR Matrix’ method and matrix-derived conditional probabilities of activity [v1; ref status: indexed, http://f1000r.es/56v

    Directory of Open Access Journals (Sweden)

    Disha Gupta-Ostermann

    2015-03-01

    Full Text Available In a previous Method Article, we have presented the ‘Structure-Activity Relationship (SAR Matrix’ (SARM approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a “chemical space envelope” around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach.

  5. Follow-up: Prospective compound design using the ‘SAR Matrix’ method and matrix-derived conditional probabilities of activity [v2; ref status: indexed, http://f1000r.es/59v

    Directory of Open Access Journals (Sweden)

    Disha Gupta-Ostermann

    2015-04-01

    Full Text Available In a previous Method Article, we have presented the ‘Structure-Activity Relationship (SAR Matrix’ (SARM approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a “chemical space envelope” around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach.

  6. Synthesis and SAR studies of novel 2-(6-aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists.

    Science.gov (United States)

    Napier, Susan E; Letourneau, Jeffrey J; Ansari, Nasrin; Auld, Douglas S; Baker, James; Best, Stuart; Campbell-Wan, Leigh; Chan, Ray; Craighead, Mark; Desai, Hema; Ho, Koc-Kan; MacSweeney, Cliona; Milne, Rachel; Richard Morphy, J; Neagu, Irina; Ohlmeyer, Michael H J; Pick, Jack; Presland, Jeremy; Riviello, Chris; Zanetakos, Heather A; Zhao, Jiuqiao; Webb, Maria L

    2011-06-15

    Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) antagonists are described. 2-(6-Aminomethylaryl-2-aryl-4-oxo-quinazolin-3(4H)-yl)acetamide have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and OT. Optimised compound 16 shows a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

    Science.gov (United States)

    Zhang, Xuqing; Li, Xiaojie; Allan, George F; Sbriscia, Tifanie; Linton, Olivia; Lundeen, Scott G; Sui, Zhihua

    2007-08-09

    A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure-activity relationships (SAR) were investigated at the R1 to R6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the R1 and R2 positions and a small group at the R5 and R6 position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.

  8. PHARUS : PHased ARray Universal SAR

    NARCIS (Netherlands)

    Paquay, M.H.A.; Vermeulen, B.C.B.; Koomen, P.J.; Hoogeboom, P.; Snoeij, P.; Pouwels, H.

    1996-01-01

    In the Netherlands, a polarimetric C-band aircraft SAR (Synthetic Aperture Radar) has been developed. The project is called PHARUS, an acronm for PHased ARray Universal SAR. This instrument serves remote sensing applications. The antenna system contains 48 active modules (expandable to 96). A module

  9. How infectious is SARS virus

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. How infectious is SARS virus. Influenza: 1 patient infects ten people. SARS: 1 patient infects 2-4 people. Incubation period 10 days. Are there `silent´ cases ? Is quarantine enough ? How will it behave if and when it returns ?

  10. Bistatic SAR: Imagery & Image Products.

    Energy Technology Data Exchange (ETDEWEB)

    Yocky, David A.; Wahl, Daniel E.; Jakowatz, Charles V,

    2014-10-01

    While typical SAR imaging employs a co-located (monostatic) RADAR transmitter and receiver, bistatic SAR imaging separates the transmitter and receiver locations. The transmitter and receiver geometry determines if the scattered signal is back scatter, forward scatter, or side scatter. The monostatic SAR image is backscatter. Therefore, depending on the transmitter/receiver collection geometry, the captured imagery may be quite different that that sensed at the monostatic SAR. This document presents imagery and image products formed from captured signals during the validation stage of the bistatic SAR research. Image quality and image characteristics are discussed first. Then image products such as two-color multi-view (2CMV) and coherent change detection (CCD) are presented.

  11. An econometric analysis of SARS and Avian flu on international tourist arrivals to Asia

    NARCIS (Netherlands)

    M.J. McAleer (Michael); B-W. Huang (Bing-Wen); H-I. Kuo (Hsiao-I); C-C. Chen (Chi-Chung); C-L. Chang (Chia-Lin)

    2008-01-01

    textabstractThis paper compares the impacts of SARS and human deaths arising from Avian Flu on international tourist arrivals to Asia. The effects of SARS and human deaths from Avian Flu will be compared directly according to human deaths. The nature of the short run and long run relationship is

  12. (Q)SAR tools for priority setting: A case study with printed paper and board food contact material substances.

    Science.gov (United States)

    Van Bossuyt, Melissa; Van Hoeck, Els; Raitano, Giuseppa; Manganelli, Serena; Braeken, Els; Ates, Gamze; Vanhaecke, Tamara; Van Miert, Sabine; Benfenati, Emilio; Mertens, Birgit; Rogiers, Vera

    2017-04-01

    Over the last years, more stringent safety requirements for an increasing number of chemicals across many regulatory fields (e.g. industrial chemicals, pharmaceuticals, food, cosmetics, …) have triggered the need for an efficient screening strategy to prioritize the substances of highest concern. In this context, alternative methods such as in silico (i.e. computational) techniques gain more and more importance. In the current study, a new prioritization strategy for identifying potentially mutagenic substances was developed based on the combination of multiple (quantitative) structure-activity relationship ((Q)SAR) tools. Non-evaluated substances used in printed paper and board food contact materials (FCM) were selected for a case study. By applying our strategy, 106 out of the 1723 substances were assigned 'high priority' as they were predicted mutagenic by 4 different (Q)SAR models. Information provided within the models allowed to identify 53 substances for which Ames mutagenicity prediction already has in vitro Ames test results. For further prioritization, additional support could be obtained by applying local i.e. specific models, as demonstrated here for aromatic azo compounds, typically found in printed paper and board FCM. The strategy developed here can easily be applied to other groups of chemicals facing the same need for priority ranking. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Mapping ground surface deformation using temporarily coherent point SAR interferometry: Application to Los Angeles Basin

    Science.gov (United States)

    Zhang, L.; Lu, Zhong; Ding, X.; Jung, H.-S.; Feng, G.; Lee, C.-W.

    2012-01-01

    Multi-temporal interferometric synthetic aperture radar (InSAR) is an effective tool to detect long-term seismotectonic motions by reducing the atmospheric artifacts, thereby providing more precise deformation signal. The commonly used approaches such as persistent scatterer InSAR (PSInSAR) and small baseline subset (SBAS) algorithms need to resolve the phase ambiguities in interferogram stacks either by searching a predefined solution space or by sparse phase unwrapping methods; however the efficiency and the success of phase unwrapping cannot be guaranteed. We present here an alternative approach – temporarily coherent point (TCP) InSAR (TCPInSAR) – to estimate the long term deformation rate without the need of phase unwrapping. The proposed approach has a series of innovations including TCP identification, TCP network and TCP least squares estimator. We apply the proposed method to the Los Angeles Basin in southern California where structurally active faults are believed capable of generating damaging earthquakes. The analysis is based on 55 interferograms from 32 ERS-1/2 images acquired during Oct. 1995 and Dec. 2000. To evaluate the performance of TCPInSAR on a small set of observations, a test with half of interferometric pairs is also performed. The retrieved TCPInSAR measurements have been validated by a comparison with GPS observations from Southern California Integrated GPS Network. Our result presents a similar deformation pattern as shown in past InSAR studies but with a smaller average standard deviation (4.6 mm) compared with GPS observations, indicating that TCPInSAR is a promising alternative for efficiently mapping ground deformation even from a relatively smaller set of interferograms.

  14. SAR calculation using FDTD simulations

    OpenAIRE

    Ferro, Francisco Nabais; Pinto, Guilherme Taveira; Pinho, Pedro

    2009-01-01

    The main intend of this work, is to determinate the Specific Absorption Rate (SAR) on human head tissues exposed to radiation caused by sources of 900 and 1800MHz, since those are the typical frequencies for mobile communications systems nowadays. In order to determinate the SAR, has been used the FDTD (Finite Difference Time Domain), which is a numeric method in time domain, obtained from the Maxwell equations in differential mode. In order to do this, a computational model from the human he...

  15. Evaluation and structure-activity relationship analysis of a new series of 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines as potential antibacterial agents

    Science.gov (United States)

    Beyzaei, Hamid; Aryan, Reza; Moghaddam-Manesh, Mohammadreza; Ghasemi, Behzad; Karimi, Pouya; Samareh Delarami, Hojat; Sanchooli, Mahmood

    2017-09-01

    The synthesis of pyrazolo[3,4-d]pyrimidine derivatives is important due to their presence in various biologically active compounds such as anticancer, antimicrobial, antiparasitic, anti-inflammatory and antidiabetic agents. In this project, a new and efficient approach for the synthesis of some novel 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines from reaction of 5-amino-pyrazole-4-carbonitrile with various hydrazides in ethanolic sodium ethoxide medium was reported. Antimicrobial activities of all synthesized derivatives were evaluated against eight Gram-positive and five Gram-negative pathogenic bacteria. The moderate to good inhibitory effects were observed based on inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. In order to determine the reasonable relationship between antibacterial activities and physiochemical properties of the derivatives, computational studies were carried out in terms of geometry optimization, short-range van der Waals forces, dipole moments, atomic charges and frontier orbital energies. It was found that both short-range forces and covalent bonds are important in the observed inhibitory effects of the molecules. The results suggested that pyrazolo[3,4-d]pyrimidine derivatives prefer a soft nucleophilic attack on bio-macromolecular targets. Furthermore, our models proposed that the antibacterial activities of these derivatives can be improved by substituting large electron donating groups on the 6-phenyl rings.

  16. Synthesis and Structure-Activity Relationships of N-Dihydrocoptisine-8-ylidene Aromatic Amines and N-Dihydrocoptisine-8-ylidene Aliphatic Amides as Antiulcerative Colitis Agents Targeting XBP1.

    Science.gov (United States)

    Xie, Meng; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Zhang, Zhi-Hui; Li, Zhi-Hong; Wang, Wen-Jie; Qin, Hai-Lin

    2016-04-22

    In this study, natural quaternary coptisine was used as a lead compound to design and synthesize structurally stable and actively potent coptisine analogues. Of the synthesized library, 13 N-dihydrocoptisine-8-ylidene amines/amides were found not only to be noncytotoxic toward intestinal epithelial cells (IECs), but they were also able to activate the transcription of X-box-binding protein 1 (XBP1) targets to varying extents in vitro. Antiulcerative colitis (UC) activity levels were assessed at the in vitro molecular level as well as in vivo in animals using multiple biomarkers as indices. In an in vitro XBP1 transcriptional activity assay, four compounds demonstrated good dose-effect relationships with EC50 values of 0.0708-0.0132 μM. Moreover, two compounds were confirmed to be more potent in vivo than a positive control, demonstrating a curative effect for UC in experimental animals. Thus, the findings of this study suggest that these coptisine analogues are promising candidates for the development of anti-UC drugs.

  17. The Danish (Q)SAR Database Update Project

    DEFF Research Database (Denmark)

    Nikolov, Nikolai Georgiev; Dybdahl, Marianne; Abildgaard Rosenberg, Sine

    2013-01-01

    The Danish (Q)SAR Database is a collection of predictions from quantitative structure–activity relationship ((Q)SAR) models for over 70 environmental and human health-related endpoints (covering biodegradation, metabolism, allergy, irritation, endocrine disruption, teratogenicity, mutagenicity......, carcinogenicity and others), each of them available for 185,000 organic substances. The database has been available online since 2005 (http://qsar.food.dtu.dk). A major update project for the Danish (Q)SAR database is under way, with a new online release planned in the beginning of 2015. The updated version...... will contain more than 600,000 discrete organic structures and new, more precise predictions for all endpoints, derived by consensus algorithms from a number of state-of-the-art individual predictions. Copyright © 2013 Published by Elsevier Ireland Ltd....

  18. Wave directional spectrum from SAR imagery

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

    Gaussian smoothed SAR image spectra have been evaluated from 512 x 512 pixel subscenes of image mode ERS-1 SAR scenes off Goa, Visakhapatnam, Paradeep and Portugal. The two recently acquired scenes off Portugal showed the signature of swell...

  19. Novel Polarimetric SAR Interferometry Algorithms, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Polarimetric radar interferometry (PolInSAR) is a new SAR imaging mode that is rapidly becoming an important technique for bare earth topographic mapping, tree...

  20. STRUCTURE – ANTIOXIDANT ACTIVITIES RELATIONSHIP ANALYSIS OF ISOEUGENOL, EUGENOL, VANILIN AND THEIR DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Nur Aini

    2010-06-01

    Full Text Available Structure Activity Relationship (SAR technique between the theoretical parameters and antioxidant activities of isoeugenol, eugenol, vanillin and their derivatives as Mannich reaction products, have been analyzed. Antioxidant activities were examined by oxidation reaction of oleic acid at 60 °C with b-carotene methods, whereas theoretical parameters of the activities were determined by calculating Bonding Dissociation Enthalpy (BDE and net charge of oxygen atom(-OH using AM1 semi empiric methods. The result from both test showed in the following orders: BHT > Mannich product of isoeugenol > isoeugenol > Mannich product of eugenol > eugenol > Mannich product of vanillin > vanillin. The antioxidant activities increase with small the BDE value and high the net charge. Electron donating groups will increase the antioxidants activity with lowering the BDE value and increasing the net charge, while electron-withdrawing groups will decrease antioxidants activity.   Keywords: SAR, antioxidants, Bonding Dissociation Entalphy, eugenol.

  1. Thapsigargin, origin, chemistry, structure-activity relationships and prodrug development

    DEFF Research Database (Denmark)

    Doan, Thi Quynh Nhu; Christensen, Søren Brøgger

    2015-01-01

    Thapsigargin was originally isolated from the roots of the Mediterranean umbelliferous plant Thapsia garganica in order to characterize the skin irritant principle. The biological activity was related to the subnanomolar affinity for the sarco-endoplasmic reticulum calcium ATPase. Prolonged......) targeted against prostate cancer. Conjugation to a peptide, which only is a substrate for prostate specific membrane antigen enabled development of a prodrug (G202), which is targeted towards a number of cancer diseases including hepatocellular carcinoma. G202 has under the name of mipsagargin in clinical...

  2. Quantitative structure-activity relationships of salicylamide neuroleptic agents.

    Science.gov (United States)

    Gupta, S P; Saha, R N; Singh, P

    1990-05-01

    The in vitro antidopamine activity of substituted N-[(1-alkyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides was found to be well correlated with the hydrophobic and electronic nature of substituents at the 3-position, and with the steric nature of groups replacing the hydrogen atom of the salicyl hydroxy group. In contrast, only the hydrophobic and steric characteristics were found to be important in the in vivo activity of these neuroleptics. This difference suggests that different mechanisms are probably involved in their in vitro and in vivo actions, and that the relevant receptors are slightly different in structure. The in vitro results suggest that electron donation by the 3-substituent strengthens the formation of a hydrogen bond between the carbonyl group of the amide moiety and a hydrogen of the receptor.

  3. Aromatic-Aromatic Interactions in Biological System: Structure Activity Relationships

    International Nuclear Information System (INIS)

    Rajagopal, Appavu; Deepa, Mohan; Govindaraju, Munisamy

    2016-01-01

    While, intramolecular hydrogen bonds have attracted the greatest attention in studies of peptide conformations, the recognition that several other weakly polar interactions may be important determinants of folded structure has been growing. Burley and Petsko provided a comprehensive overview of the importance of weakly polar interactions, in shaping protein structures. The interactions between aromatic rings, which are spatially approximate, have attracted special attention. A survey of the proximal aromatic residue pairs in proteins, allowed Burley and Petsko to suggest that, “phenyl ring centroids are separated by a preferential distance of between 4.5 and 7 Å, and dihedral angles approximately 90° are most common”

  4. Preliminary structure-activity relationship studies on some novel s ...

    African Journals Online (AJOL)

    yl)-1, 3, 4-oxadiazole-2-thiol were synthesized through reaction with different saturated and unsaturated ... inhibitor, while compound 5b with n-propyl substitution is a strong antibacterial agent. ... sulfonyl chloride (30 mmol) in 30 mL distilled.

  5. Structure-activity relationship of immunostimulatory effects of phthalates

    Directory of Open Access Journals (Sweden)

    Nielsen Gunnar D

    2008-10-01

    Full Text Available Abstract Background Some chemicals, including some phthalate plasticizers, have been shown to have an adjuvant effect in mice. However, an adjuvant effect, defined as an inherent ability to stimulate the humoral immune response, was only observed after exposure to a limited number of the phthalates. An adjuvant effect may be due to the structure or physicochemical characteristics of the molecule. The scope of this study was to investigate which molecular characteristics that determine the observed adjuvant effect of the most widely used phthalate plasticizer, the di-(2-ethylhexyl phthalate (DEHP, which is documented as having a strong adjuvant effect. To do so, a series of nine lipophilic compounds with structural and physicochemical relations to DEHP were investigated. Results Adjuvant effect of phthalates and related compounds were restricted to the IgG1 antibody formation. No effect was seen on IgE. It appears that lipophilicity plays a crucial role, but lipophilicity does not per se cause an adjuvant effect. In addition to lipophilicity, a phthalate must also possess specific stereochemical characteristics in order for it to have adjuvant effect. Conclusion The adjuvant effect of phthalates are highly influenced by both stereochemical and physico-chemical properties. This knowledge may be used in the rational development of plasticizers without adjuvant effect as well as in the design of new immunological adjuvants.

  6. Aromatic-Aromatic Interactions in Biological System: Structure Activity Relationships

    Energy Technology Data Exchange (ETDEWEB)

    Rajagopal, Appavu; Deepa, Mohan [Molecular Biophysics Unit, Indian Institute of Sciences-Bangalore, Karnataka (India); Govindaraju, Munisamy [Bio-Spatial Technology Research Unit, Department of Environmental Biotechnology, School of Environmental Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu (India)

    2016-02-26

    While, intramolecular hydrogen bonds have attracted the greatest attention in studies of peptide conformations, the recognition that several other weakly polar interactions may be important determinants of folded structure has been growing. Burley and Petsko provided a comprehensive overview of the importance of weakly polar interactions, in shaping protein structures. The interactions between aromatic rings, which are spatially approximate, have attracted special attention. A survey of the proximal aromatic residue pairs in proteins, allowed Burley and Petsko to suggest that, “phenyl ring centroids are separated by a preferential distance of between 4.5 and 7 Å, and dihedral angles approximately 90° are most common”.

  7. SAR matrices: automated extraction of information-rich SAR tables from large compound data sets.

    Science.gov (United States)

    Wassermann, Anne Mai; Haebel, Peter; Weskamp, Nils; Bajorath, Jürgen

    2012-07-23

    We introduce the SAR matrix data structure that is designed to elucidate SAR patterns produced by groups of structurally related active compounds, which are extracted from large data sets. SAR matrices are systematically generated and sorted on the basis of SAR information content. Matrix generation is computationally efficient and enables processing of large compound sets. The matrix format is reminiscent of SAR tables, and SAR patterns revealed by different categories of matrices are easily interpretable. The structural organization underlying matrix formation is more flexible than standard R-group decomposition schemes. Hence, the resulting matrices capture SAR information in a comprehensive manner.

  8. Distributing Correlation Coefficients of Linear Structure-Activity/Property Models

    Directory of Open Access Journals (Sweden)

    Sorana D. BOLBOACA

    2011-12-01

    Full Text Available Quantitative structure-activity/property relationships are mathematical relationships linking chemical structure and activity/property in a quantitative manner. These in silico approaches are frequently used to reduce animal testing and risk-assessment, as well as to increase time- and cost-effectiveness in characterization and identification of active compounds. The aim of our study was to investigate the pattern of correlation coefficients distribution associated to simple linear relationships linking the compounds structure with their activities. A set of the most common ordnance compounds found at naval facilities with a limited data set with a range of toxicities on aquatic ecosystem and a set of seven properties was studied. Statistically significant models were selected and investigated. The probability density function of the correlation coefficients was investigated using a series of possible continuous distribution laws. Almost 48% of the correlation coefficients proved fit Beta distribution, 40% fit Generalized Pareto distribution, and 12% fit Pert distribution.

  9. Convolutional Neural Networks for SAR Image Segmentation

    DEFF Research Database (Denmark)

    Malmgren-Hansen, David; Nobel-Jørgensen, Morten

    2015-01-01

    Segmentation of Synthetic Aperture Radar (SAR) images has several uses, but it is a difficult task due to a number of properties related to SAR images. In this article we show how Convolutional Neural Networks (CNNs) can easily be trained for SAR image segmentation with good results. Besides...

  10. Imaging in severe acute respiratory syndrome (SARS)

    International Nuclear Information System (INIS)

    Antonio, G.E.; Wong, K.T.; Chu, W.C.W.; Hui, D.S.C.; Cheng, F.W.T.; Yuen, E.H.Y.; Chung, S.S.C.; Fok, T.F.; Sung, J.J.Y.; Ahuja, A.T.

    2003-01-01

    Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus, and has become pandemic within a short period of time. Imaging plays an important role in the diagnosis, management and follow-up of patients with SARS. The current status of imaging in SARS is presented in this review

  11. Precision Rectification of Airborne SAR Image

    DEFF Research Database (Denmark)

    Dall, Jørgen; Liao, M.; Zhang, Zhe

    1997-01-01

    A simple and direct procedure for the rectification of a certain class of airborne SAR data is presented. The relief displacements of SAR data are effectively removed by means of a digital elevation model and the image is transformed to the ground coordinate system. SAR data from the Danish EMISAR...

  12. Polarimetric scattering and SAR information retrieval

    CERN Document Server

    Jin, Ya-Qiu

    2013-01-01

    Taking an innovative look at Synthetic Aperture Radar (SAR), this practical reference fully covers new developments in SAR and its various methodologies and enables readers to interpret SAR imagery An essential reference on polarimetric Synthetic Aperture Radar (SAR), this book uses scattering theory and radiative transfer theory as a basis for its treatment of topics. It is organized to include theoretical scattering models and SAR data analysis techniques, and presents cutting-edge research on theoretical modelling of terrain surface. The book includes quantitative app

  13. Dillapiole as antileishmanial agent: discovery, cytotoxic activity and preliminary SAR studies of dillapiole analogues.

    Science.gov (United States)

    Parise-Filho, Roberto; Pasqualoto, Kerly Fernanda Mesquita; Magri, Fátima Maria Motter; Ferreira, Adilson Kleber; da Silva, Bárbara Athayde Vaz Galvão; Damião, Mariana Celestina Frojuello Costa Bernstorff; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Auada, Aline Vivian Vatti; Polli, Michelle Carneiro; Brandt, Carlos Alberto

    2012-12-01

    In this paper, the isolation of dillapiole (1) from Piper aduncum was reported as well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole (2), isodillapiole (3)], via reduction and isomerization reactions. Also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structure-activity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC(50)  = 69.3 µM) and Leishmania brasiliensis (IC(50)  = 59.4 µM) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC(50)  = 99.9 µM for L. amazonensis and IC(50)  = 90.5 µM for L. braziliensis) and 3 (IC(50)  = 122.9 µM for L. amazonensis and IC(50)  = 109.8 µM for L. brasiliensis) were less active than dillapiole (1). Regarding the molecular properties, the conformational arrangement of the side chain, electronic features, and the hydrophilic/hydrophobic balance seem to be relevant for explaining the antileishmanial activity of dillapiole and its analogues. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Stalking SARS: CDC at Work

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about the SARS outbreak and how CDC worked to solve the mystery.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  15. SARS – virus jumps species

    Indian Academy of Sciences (India)

    SARS – virus jumps species. Coronavirus reshuffles genes; Rotteir et al, Rotterdam showed the virus to jump from cats to mouse cells after single gene mutation ? Human disease due to virus jumping from wild or domestic animals; Present favourite animal - the cat; - edible or domestic.

  16. Urban Aerodynamic Roughness Length Mapping Using Multitemporal SAR Data

    Directory of Open Access Journals (Sweden)

    Fengli Zhang

    2017-01-01

    Full Text Available Aerodynamic roughness is very important to urban meteorological and climate studies. Radar remote sensing is considered to be an effective means for aerodynamic roughness retrieval because radar backscattering is sensitive to the surface roughness and geometric structure of a given target. In this paper, a methodology for aerodynamic roughness length estimation using SAR data in urban areas is introduced. The scale and orientation characteristics of backscattering of various targets in urban areas were firstly extracted and analyzed, which showed great potential of SAR data for urban roughness elements characterization. Then the ground truth aerodynamic roughness was calculated from wind gradient data acquired by the meteorological tower using fitting and iterative method. And then the optimal dimension of the upwind sector for the aerodynamic roughness calculation was determined through a correlation analysis between backscattering extracted from SAR data at various upwind sector areas and the aerodynamic roughness calculated from the meteorological tower data. Finally a quantitative relationship was set up to retrieve the aerodynamic roughness length from SAR data. Experiments based on ALOS PALSAR and COSMO-SkyMed data from 2006 to 2011 prove that the proposed methodology can provide accurate roughness length estimations for the spatial and temporal analysis of urban surface.

  17. Classification of sea-ice types in SAR imagery

    International Nuclear Information System (INIS)

    Baraldi, A.; Parmiggiani, F.

    2001-01-01

    It is presented a supervised three-stage classification (labeling) scheme applied to SAR images of polar regions for detecting different sea-ice types. The three-stage labeling procedure consists of: 1) a speckle noise filtering stage, based on a sequence of contour detection, segmentation and filtering steps, which removes SAR speckle noise (and texture information as well) without losing spatial details; 2) a second stage providing Bayesian, maximum-α-posteriori, hierarchical (coarse-to-fine), adaptive (data-driven) and contextual labeling of piecewise constant intensity images featuring little useful texture information; and 3) an output stage providing a many-to-one relationship between second stage output categories (types or clusters) and desired output classes. Modules 1) and 2), which demonstrated their validity in several applications in the existing literature, are briefly recalled in the current paper. The proposed labeling scheme features some interesting functional properties when applied to sea-ice SAR images: it is easy to use, i.e., it requires minor user interaction, is robust to changes in input conditions and performs better than a non-contextual (per-pixel) classifier. Application results are presented and discussed for a pair of SAR images extracted, respectively, from an ERS-1 scene acquired on November 1992 over the Bellingshausen Sea (Antarctica) and from an ERS-2 scene of the East Greenland Sea acquired on March 1997 when a field experiment by the research vessel Jan Ma yen was conducted in the same area

  18. Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues.

    Science.gov (United States)

    Vallone, Alessandra; D'Alessandro, Sarah; Brogi, Simone; Brindisi, Margherita; Chemi, Giulia; Alfano, Gloria; Lamponi, Stefania; Lee, Soon Goo; Jez, Joseph M; Koolen, Karin J M; Dechering, Koen J; Saponara, Simona; Fusi, Fabio; Gorelli, Beatrice; Taramelli, Donatella; Parapini, Silvia; Caldelari, Reto; Campiani, Giuseppe; Gemma, Sandra; Butini, Stefania

    2018-04-25

    Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba 2+ current through Ca v 1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  19. SARS and Population Health Technology

    OpenAIRE

    Eysenbach, Gunther

    2003-01-01

    The recent global outbreak of SARS (severe acute respiratory syndrome) provides an opportunity to study the use and impact of public health informatics and population health technology to detect and fight a global epidemic. Population health technology is the umbrella term for technology applications that have a population focus and the potential to improve public health. This includes the Internet, but also other technologies such as wireless devices, mobile phones, smart appliances, or smar...

  20. SARS-related perceptions in Hong Kong.

    Science.gov (United States)

    Lau, Joseph T F; Yang, Xilin; Pang, Ellie; Tsui, H Y; Wong, Eric; Wing, Yun Kwok

    2005-03-01

    To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and approximately equals 70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and approximately equals 40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.

  1. SARS-related Perceptions in Hong Kong

    OpenAIRE

    Lau, Joseph T.F.; Yang, Xilin; Pang, Ellie; Tsui, H.Y.; Wong, Eric; Wing, Yun Kwok

    2005-01-01

    To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means o...

  2. SAR system development for UAV multicopter platforms

    OpenAIRE

    Escartin Martínez, Antonio

    2015-01-01

    SAR system development for UAV multicopter platforms This thesis describes the optimization of a synthetic aperture radar (SAR) at X-band and its integration into an unmanned aerial vehicle (UAV) of type octocopter. For such optimization the SAR system functionality was extended from singlepol to fulpol and it has been optimized at hardware level in order to improve its quality against noise figure. After its integration into the octocopter platform, its features has been used in order to ...

  3. Sentinel-3 SAR Altimetry Toolbox

    Science.gov (United States)

    Benveniste, Jerome; Lucas, Bruno; DInardo, Salvatore

    2015-04-01

    The prime objective of the SEOM (Scientific Exploitation of Operational Missions) element is to federate, support and expand the large international research community that the ERS, ENVISAT and the Envelope programmes have build up over the last 20 years for the future European operational Earth Observation missions, the Sentinels. Sentinel-3 builds directly on a proven heritage of ERS-2 and Envisat, and CryoSat-2, with a dual-frequency (Ku and C band) advanced Synthetic Aperture Radar Altimeter (SRAL) that provides measurements at a resolution of ~300m in SAR mode along track. Sentinel-3 will provide exact measurements of sea-surface height along with accurate topography measurements over sea ice, ice sheets, rivers and lakes. The first of the two Sentinels is expected to be launched in early 2015. The current universal altimetry toolbox is BRAT (Basic Radar Altimetry Toolbox) which can read all previous and current altimetry mission's data, but it does not have the capabilities to read the upcoming Sentinel-3 L1 and L2 products. ESA will endeavour to develop and supply this capability to support the users of the future Sentinel-3 SAR Altimetry Mission. BRAT is a collection of tools and tutorial documents designed to facilitate the processing of radar altimetry data. This project started in 2005 from the joint efforts of ESA (European Space Agency) and CNES (Centre National d'Etudes Spatiales), and it is freely available at http://earth.esa.int/brat. The tools enable users to interact with the most common altimetry data formats, the BratGUI is the front-end for the powerful command line tools that are part of the BRAT suite. BRAT can also be used in conjunction with Matlab/IDL (via reading routines) or in C/C++/Fortran via a programming API, allowing the user to obtain desired data, bypassing the data-formatting hassle. BRAT can be used simply to visualise data quickly, or to translate the data into other formats such as netCDF, ASCII text files, KML (Google Earth

  4. N-Substituted 5-Chloro-6-phenylpyridazin-3(2H-ones: Synthesis, Insecticidal Activity Against Plutella xylostella (L. and SAR Study

    Directory of Open Access Journals (Sweden)

    Song Yang

    2012-08-01

    Full Text Available A series of N-substituted 5-chloro-6-phenylpyridazin-3(2H-one derivatives were synthesized based on our previous work; all compounds were characterized by spectral data and tested for in vitro insecticidal activity against Plutella xylostella. The results showed that the synthesized pyridazin-3(2H-one compounds possessed good insecticidal activities, especially the compounds 4b, 4d, and 4h which showed > 90% activity at 100 mg/L. The structure-activity relationships (SAR for these compounds were also discussed.

  5. Geometric calibration of ERS satellite SAR images

    DEFF Research Database (Denmark)

    Mohr, Johan Jacob; Madsen, Søren Nørvang

    2001-01-01

    Geometric calibration of the European Remote Sensing (ERS) Satellite synthetic aperture radar (SAR) slant range images is important in relation to mapping areas without ground reference points and also in relation to automated processing. The relevant SAR system parameters are discussed...

  6. PHARUS: A C-band Airborne SAR

    NARCIS (Netherlands)

    Hoogeboom, P.; Koomen, P.J.; Pouwels, H.; Snoeij, P.

    1990-01-01

    In The Netherlands a plan to design aircraft and build a polarimetric C-band SAR system of a novel design, called PHARUS (PHased Array Universal SAR) is carried out by three institutes. These institutes are the Physics and Electronics Laboratory TNO in The Hague (prime contractor and project

  7. SARS – Koch´Postulates proved.

    Indian Academy of Sciences (India)

    SARS – Koch´Postulates proved. Novel coronavirus identified from fluids of patients. Virus cultured in Vero cell line. Sera of patients have antibodies to virus. Cultured virus produces disease in Macaque monkeys. -produces specific immune response; -isolated virus is SARS CoV; -pathology similar to human.

  8. Deep learning for SAR image formation

    Science.gov (United States)

    Mason, Eric; Yonel, Bariscan; Yazici, Birsen

    2017-04-01

    The recent success of deep learning has lead to growing interest in applying these methods to signal processing problems. This paper explores the applications of deep learning to synthetic aperture radar (SAR) image formation. We review deep learning from a perspective relevant to SAR image formation. Our objective is to address SAR image formation in the presence of uncertainties in the SAR forward model. We present a recurrent auto-encoder network architecture based on the iterative shrinkage thresholding algorithm (ISTA) that incorporates SAR modeling. We then present an off-line training method using stochastic gradient descent and discuss the challenges and key steps of learning. Lastly, we show experimentally that our method can be used to form focused images in the presence of phase uncertainties. We demonstrate that the resulting algorithm has faster convergence and decreased reconstruction error than that of ISTA.

  9. SARS: systematic review of treatment effects.

    Directory of Open Access Journals (Sweden)

    Lauren J Stockman

    2006-09-01

    Full Text Available BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r, type I interferon (IFN, intravenous immunoglobulin (IVIG, and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage

  10. SARS and population health technology.

    Science.gov (United States)

    Eysenbach, Gunther

    2003-01-01

    The recent global outbreak of SARS (severe acute respiratory syndrome) provides an opportunity to study the use and impact of public health informatics and population health technology to detect and fight a global epidemic. Population health technology is the umbrella term for technology applications that have a population focus and the potential to improve public health. This includes the Internet, but also other technologies such as wireless devices, mobile phones, smart appliances, or smart homes. In the context of an outbreak or bioterrorism attack, such technologies may help to gather intelligence and detect diseases early, and communicate and exchange information electronically worldwide. Some of the technologies brought forward during the SARS epidemic may have been primarily motivated by marketing efforts, or were more directed towards reassuring people that "something is being done," ie, fighting an "epidemic of fear." To understand "fear epidemiology" is important because early warning systems monitoring data from a large number of people may not be able to discriminate between a biological epidemic and an epidemic of fear. The need for critical evaluation of all of these technologies is stressed.

  11. A Spectral-SAR Model for the Anionic-Cationic Interaction in Ionic Liquids: Application to Vibrio fischeri Ecotoxicity

    Directory of Open Access Journals (Sweden)

    Vasile Ostafe

    2007-08-01

    Full Text Available Within the recently launched the spectral-structure activity relationship (S-SARanalysis, the vectorial anionic-cationic model of a generic ionic liquid is proposed, alongwith the associated algebraic correlation factor in terms of the measured and predictedactivity norms. The reliability of the present scheme is tested by assessing the Hanschfactors, i.e. lipophylicity, polarizability and total energy, to predict the ecotoxicityendpoints of wide types of ionic liquids with ammonium, pyridinium, phosphonium,choline and imidazolium cations on the aquatic bacteria Vibrio fischeri. The results, whileconfirming the cationic dominant influence when only lipophylicity is considered,demonstrate that the anionic effect dominates all other more specific interactions. It wasalso proved that the S-SAR vectorial model predicts considerably higher activity for theionic liquids than for its anionic and cationic subsystems separately, in all consideredcases. Moreover, through applying the least norm-correlation path principle, the completetoxicological hierarchies are presented, unfolding the ecological rules of combined cationicand anionic influences in ionic liquid toxicity.

  12. SAR and LIDAR fusion: experiments and applications

    Science.gov (United States)

    Edwards, Matthew C.; Zaugg, Evan C.; Bradley, Joshua P.; Bowden, Ryan D.

    2013-05-01

    In recent years ARTEMIS, Inc. has developed a series of compact, versatile Synthetic Aperture Radar (SAR) systems which have been operated on a variety of small manned and unmanned aircraft. The multi-frequency-band SlimSAR has demonstrated a variety of capabilities including maritime and littoral target detection, ground moving target indication, polarimetry, interferometry, change detection, and foliage penetration. ARTEMIS also continues to build upon the radar's capabilities through fusion with other sensors, such as electro-optical and infrared camera gimbals and light detection and ranging (LIDAR) devices. In this paper we focus on experiments and applications employing SAR and LIDAR fusion. LIDAR is similar to radar in that it transmits a signal which, after being reflected or scattered by a target area, is recorded by the sensor. The differences are that a LIDAR uses a laser as a transmitter and optical sensors as a receiver, and the wavelengths used exhibit a very different scattering phenomenology than the microwaves used in radar, making SAR and LIDAR good complementary technologies. LIDAR is used in many applications including agriculture, archeology, geo-science, and surveying. Some typical data products include digital elevation maps of a target area and features and shapes extracted from the data. A set of experiments conducted to demonstrate the fusion of SAR and LIDAR data include a LIDAR DEM used in accurately processing the SAR data of a high relief area (mountainous, urban). Also, feature extraction is used in improving geolocation accuracy of the SAR and LIDAR data.

  13. Structural classification of marshes with Polarimetric SAR highlighting the temporal mapping of marshes exposed to oil

    Science.gov (United States)

    Ramsey, Elijah W.; Rangoonwala, Amina; Jones, Cathleen E.

    2015-01-01

    Empirical relationships between field-derived Leaf Area Index (LAI) and Leaf Angle Distribution (LAD) and polarimetric synthetic aperture radar (PolSAR) based biophysical indicators were created and applied to map S. alterniflora marsh canopy structure. PolSAR and field data were collected near concurrently in the summers of 2010, 2011, and 2012 in coastal marshes, and PolSAR data alone were acquired in 2009. Regression analyses showed that LAI correspondence with the PolSAR biophysical indicator variables equaled or exceeded those of vegetation water content (VWC) correspondences. In the final six regressor model, the ratio HV/VV explained 49% of the total 77% explained LAI variance, and the HH-VV coherence and phase information accounted for the remainder. HV/HH dominated the two regressor LAD relationship, and spatial heterogeneity and backscatter mechanism followed by coherence information dominated the final three regressor model that explained 74% of the LAD variance. Regression results applied to 2009 through 2012 PolSAR images showed substantial changes in marsh LAI and LAD. Although the direct cause was not substantiated, following a release of freshwater in response to the 2010 Deepwater Horizon oil spill, the fairly uniform interior marsh structure of 2009 was more vertical and dense shortly after the oil spill cessation. After 2010, marsh structure generally progressed back toward the 2009 uniformity; however, the trend was more disjointed in oil impact marshes.             

  14. Structural Classification of Marshes with Polarimetric SAR Highlighting the Temporal Mapping of Marshes Exposed to Oil

    Directory of Open Access Journals (Sweden)

    Elijah Ramsey

    2015-09-01

    Full Text Available Empirical relationships between field-derived Leaf Area Index (LAI and Leaf Angle Distribution (LAD and polarimetric synthetic aperture radar (PolSAR based biophysical indicators were created and applied to map S. alterniflora marsh canopy structure. PolSAR and field data were collected near concurrently in the summers of 2010, 2011, and 2012 in coastal marshes, and PolSAR data alone were acquired in 2009. Regression analyses showed that LAI correspondence with the PolSAR biophysical indicator variables equaled or exceeded those of vegetation water content (VWC correspondences. In the final six regressor model, the ratio HV/VV explained 49% of the total 77% explained LAI variance, and the HH-VV coherence and phase information accounted for the remainder. HV/HH dominated the two regressor LAD relationship, and spatial heterogeneity and backscatter mechanism followed by coherence information dominated the final three regressor model that explained 74% of the LAD variance. Regression results applied to 2009 through 2012 PolSAR images showed substantial changes in marsh LAI and LAD. Although the direct cause was not substantiated, following a release of freshwater in response to the 2010 Deepwater Horizon oil spill, the fairly uniform interior marsh structure of 2009 was more vertical and dense shortly after the oil spill cessation. After 2010, marsh structure generally progressed back toward the 2009 uniformity; however, the trend was more disjointed in oil impact marshes.

  15. Wave directional spectrum from SAR imagery

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Sarma, Y.V.B.; Menon, H.B.; Vethamony, P.

    < 2m and the zero-crossing period during the satellite overpass is small (< 6s, �O�O < 60m). We therefore utilized the visit of one of the authors (Sarma) to the Southampton Oceanographic Centre, U.K., to procure two ERS-1 digital image mode SAR...-dimensional FFT as well as a computer program for downloading SAR data from CCT. Finally we owe a debt of gratitude to J C da Silva, Southampton Oceanographic Centre, U K for sharing some of his SAR data with us. References Allan T. D. (Ed) (1983...

  16. Evaluation and SAR analysis of the cytotoxicity of tanshinones in colon cancer cells.

    Science.gov (United States)

    Wang, Lin; Liu, An; Zhang, Fei-Long; Yeung, John H K; Li, Xu-Qin; Cho, Chi-Hin

    2014-03-01

    This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action. Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM). Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53(+/+) colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells. The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  17. Probing the Hypothesis of SAR Continuity Restoration by the Removal of Activity Cliffs Generators in QSAR.

    Science.gov (United States)

    Cruz-Monteagudo, Maykel; Medina-Franco, José L; Perera-Sardiña, Yunier; Borges, Fernanda; Tejera, Eduardo; Paz-Y-Miño, Cesar; Pérez-Castillo, Yunierkis; Sánchez-Rodríguez, Aminael; Contreras-Posada, Zuleidys; Cordeiro, M Natália D S

    2016-01-01

    In this work we report the first attempt to study the effect of activity cliffs over the generalization ability of machine learning (ML) based QSAR classifiers, using as study case a previously reported diverse and noisy dataset focused on drug induced liver injury (DILI) and more than 40 ML classification algorithms. Here, the hypothesis of structure-activity relationship (SAR) continuity restoration by activity cliffs removal is tested as a potential solution to overcome such limitation. Previously, a parallelism was established between activity cliffs generators (ACGs) and instances that should be misclassified (ISMs), a related concept from the field of machine learning. Based on this concept we comparatively studied the classification performance of multiple machine learning classifiers as well as the consensus classifier derived from predictive classifiers obtained from training sets including or excluding ACGs. The influence of the removal of ACGs from the training set over the virtual screening performance was also studied for the respective consensus classifiers algorithms. In general terms, the removal of the ACGs from the training process slightly decreased the overall accuracy of the ML classifiers and multi-classifiers, improving their sensitivity (the weakest feature of ML classifiers trained with ACGs) but decreasing their specificity. Although these results do not support a positive effect of the removal of ACGs over the classification performance of ML classifiers, the "balancing effect" of ACG removal demonstrated to positively influence the virtual screening performance of multi-classifiers based on valid base ML classifiers. Specially, the early recognition ability was significantly favored after ACGs removal. The results presented and discussed in this work represent the first step towards the application of a remedial solution to the activity cliffs problem in QSAR studies.

  18. New cholinesterase inhibitors for Alzheimer's disease: Structure Activity Studies (SARs) and molecular docking of isoquinolone and azepanone derivatives.

    Science.gov (United States)

    Bacalhau, Patrícia; San Juan, Amor A; Marques, Carolina S; Peixoto, Daniela; Goth, Albertino; Guarda, Cátia; Silva, Mara; Arantes, Sílvia; Caldeira, A Teresa; Martins, Rosário; Burke, Anthony J

    2016-08-01

    A library of isoquinolinone and azepanone derivatives were screened for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. The strategy adopted included (a) in vitro biological assays, against eel AChE (EeAChE) and equine serum BuChE (EqBuChE) in order to determine the compounds IC50 and their dose-response activity, consolidated by (b) molecular docking studies to evaluate the docking poses and interatomic interactions in the case of the hit compounds, validated by STD-NMR studies. Compound (1f) was identified as one of these hits with an IC50 of 89.5μM for EeAChE and 153.8μM for EqBuChE, (2a) was identified as a second hit with an IC50 of 108.4μM (EeAChE) and 277.8μM (EqBuChE). In order to gain insights into the binding mode and principle active site interactions of these molecules, (R)-(1f) along with 3 other analogues (also as the R-enantiomer) were docked into both RhAChE and hBuChE models. Galantamine was used as the benchmark. The docking study was validated by performing an STD-NMR study of (1f) with EeAChE using galantamine as the benchmark. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. AUTOMATIC INTERPRETATION OF HIGH RESOLUTION SAR IMAGES: FIRST RESULTS OF SAR IMAGE SIMULATION FOR SINGLE BUILDINGS

    Directory of Open Access Journals (Sweden)

    J. Tao

    2012-09-01

    Full Text Available Due to the all-weather data acquisition capabilities, high resolution space borne Synthetic Aperture Radar (SAR plays an important role in remote sensing applications like change detection. However, because of the complex geometric mapping of buildings in urban areas, SAR images are often hard to interpret. SAR simulation techniques ease the visual interpretation of SAR images, while fully automatic interpretation is still a challenge. This paper presents a method for supporting the interpretation of high resolution SAR images with simulated radar images using a LiDAR digital surface model (DSM. Line features are extracted from the simulated and real SAR images and used for matching. A single building model is generated from the DSM and used for building recognition in the SAR image. An application for the concept is presented for the city centre of Munich where the comparison of the simulation to the TerraSAR-X data shows a good similarity. Based on the result of simulation and matching, special features (e.g. like double bounce lines, shadow areas etc. can be automatically indicated in SAR image.

  20. Combined DEM Extration Method from StereoSAR and InSAR

    Science.gov (United States)

    Zhao, Z.; Zhang, J. X.; Duan, M. Y.; Huang, G. M.; Yang, S. C.

    2015-06-01

    A pair of SAR images acquired from different positions can be used to generate digital elevation model (DEM). Two techniques exploiting this characteristic have been introduced: stereo SAR and interferometric SAR. They permit to recover the third dimension (topography) and, at the same time, to identify the absolute position (geolocation) of pixels included in the imaged area, thus allowing the generation of DEMs. In this paper, StereoSAR and InSAR combined adjustment model are constructed, and unify DEM extraction from InSAR and StereoSAR into the same coordinate system, and then improve three dimensional positioning accuracy of the target. We assume that there are four images 1, 2, 3 and 4. One pair of SAR images 1,2 meet the required conditions for InSAR technology, while the other pair of SAR images 3,4 can form stereo image pairs. The phase model is based on InSAR rigorous imaging geometric model. The master image 1 and the slave image 2 will be used in InSAR processing, but the slave image 2 is only used in the course of establishment, and the pixels of the slave image 2 are relevant to the corresponding pixels of the master image 1 through image coregistration coefficient, and it calculates the corresponding phase. It doesn't require the slave image in the construction of the phase model. In Range-Doppler (RD) model, the range equation and Doppler equation are a function of target geolocation, while in the phase equation, the phase is also a function of target geolocation. We exploit combined adjustment model to deviation of target geolocation, thus the problem of target solution is changed to solve three unkonwns through seven equations. The model was tested for DEM extraction under spaceborne InSAR and StereoSAR data and compared with InSAR and StereoSAR methods respectively. The results showed that the model delivered a better performance on experimental imagery and can be used for DEM extraction applications.

  1. Monitoring informal settlements using SAR polarimetry

    CSIR Research Space (South Africa)

    Kleynhans, W

    2012-10-01

    Full Text Available for settlement mapping and detection has remained largely unexplored in Southern Africa. The objective of this study is to investigate the possible role that SAR polarimetry could play in the monitoring of informal settlements....

  2. Work session on the SAR. Pt. 2

    International Nuclear Information System (INIS)

    Burkart, K.

    1980-01-01

    The present paper contains the tables of the contribution of K. Burkart 'Work Session on the SAR' to the IAEA Interregional Training Course held in Sept/Oct. 1980 at the Kernforschungszentrum Karlsruhe. (RW)

  3. Image based SAR product simulation for analysis

    Science.gov (United States)

    Domik, G.; Leberl, F.

    1987-01-01

    SAR product simulation serves to predict SAR image gray values for various flight paths. Input typically consists of a digital elevation model and backscatter curves. A new method is described of product simulation that employs also a real SAR input image for image simulation. This can be denoted as 'image-based simulation'. Different methods to perform this SAR prediction are presented and advantages and disadvantages discussed. Ascending and descending orbit images from NASA's SIR-B experiment were used for verification of the concept: input images from ascending orbits were converted into images from a descending orbit; the results are compared to the available real imagery to verify that the prediction technique produces meaningful image data.

  4. Attribute Learning for SAR Image Classification

    Directory of Open Access Journals (Sweden)

    Chu He

    2017-04-01

    Full Text Available This paper presents a classification approach based on attribute learning for high spatial resolution Synthetic Aperture Radar (SAR images. To explore the representative and discriminative attributes of SAR images, first, an iterative unsupervised algorithm is designed to cluster in the low-level feature space, where the maximum edge response and the ratio of mean-to-variance are included; a cross-validation step is applied to prevent overfitting. Second, the most discriminative clustering centers are sorted out to construct an attribute dictionary. By resorting to the attribute dictionary, a representation vector describing certain categories in the SAR image can be generated, which in turn is used to perform the classifying task. The experiments conducted on TerraSAR-X images indicate that those learned attributes have strong visual semantics, which are characterized by bright and dark spots, stripes, or their combinations. The classification method based on these learned attributes achieves better results.

  5. SARS Patients and Their Close Contacts

    Science.gov (United States)

    ... Outreach Workers VIII. Infection Control for Laboratory and Pathology Procedures IX. Occupational Health Issues Appendix I1 Appendix ... SARS was recognized as a global threat in March 2003, after first appearing in Southern China in ...

  6. Multiple Input - Multiple Output (MIMO) SAR

    Data.gov (United States)

    National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

  7. SAR Ambiguity Study for the Cassini Radar

    Science.gov (United States)

    Hensley, Scott; Im, Eastwood; Johnson, William T. K.

    1993-01-01

    The Cassini Radar's synthetic aperture radar (SAR) ambiguity analysis is unique with respect to other spaceborne SAR ambiguity analyses owing to the non-orbiting spacecraft trajectory, asymmetric antenna pattern, and burst mode of data collection. By properly varying the pointing, burst mode timing, and radar parameters along the trajectory this study shows that the signal-to-ambiguity ratio of better than 15 dB can be achieved for all images obtained by the Cassini Radar.

  8. Estimating Elevation Angles From SAR Crosstalk

    Science.gov (United States)

    Freeman, Anthony

    1994-01-01

    Scheme for processing polarimetric synthetic-aperture-radar (SAR) image data yields estimates of elevation angles along radar beam to target resolution cells. By use of estimated elevation angles, measured distances along radar beam to targets (slant ranges), and measured altitude of aircraft carrying SAR equipment, one can estimate height of target terrain in each resolution cell. Monopulselike scheme yields low-resolution topographical data.

  9. SARS: Key factors in crisis management.

    Science.gov (United States)

    Tseng, Hsin-Chao; Chen, Thai-Form; Chou, Shieu-Ming

    2005-03-01

    This study was conducted at a single hospital selected in Taipei during the SARS (Severe Acute Respiratory Syndrome) outbreak from March to July, 2003 in Taiwan. During this period of time, 104 SARS patients were admitted to the hospital. There were no negative reports related to the selected hospital despite its being located right in the center of an area struck by the epidemic. The purpose of this study was to identify the key factors enabling the hospital to survive SARS unscathed. Data were collected from in-depth interviews with the nursing directors and nursing managers of the SARS units, along with a review of relevant hospital documents. The five key elements identified as survival factors during this SARS crisis are as follows: 1. good control of timing for crisis management, 2. careful decision-making, 3. thorough implementation, 4. effective communication, and 5. trust between management and employees. The results of this study reconfirmed the selected hospital as a model for good crisis management during the SARS epidemic.

  10. Trichothecenes: structure-toxic activity relationships.

    Science.gov (United States)

    Wu, Qinghua; Dohnal, Vlastimil; Kuca, Kamil; Yuan, Zonghui

    2013-07-01

    Trichothecenes comprise a large family of structurally related toxins mainly produced by fungi belonging to the genus Fusarium. Among trichothecenes, type A and type B are of the most concern due to their broad and highly toxic nature. In order to address structure-activity relationships (SAR) of trichothecenes, relationships between structural features and biological effects of trichothecene mycotoxins in mammalian systems are summarized in this paper. The double bond between C-9-C-10 and the 12,13-epoxide ring are essential structural features for trichothecene toxicity. Removal of these groups results in a complete loss of toxicity. A hydroxyl group at C-3 enhances trichothecene toxicity, while this activity decreases gradually when C-3 is substituted with either hydrogen or an acetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower toxicity than an acetoxy group at the same position. The toxicity for type B trichothecenes decreases if the substituent at C-4 is changed from acetoxy to hydroxyl or hydrogen at C-4 position. The presence of hydroxyl and hydrogen groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy group attached to this carbon. Trichothecenes toxicity increases when a macrocyclic ring exists between the C-4 and C-15. At C-8 position, an oxygenated substitution at C-8 is essential for trichothecene toxicity, indicating a decrease in the toxicity if substituent change from isovaleryloxy through hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8 reduces the toxicity, whereas epoxidation at C-9-C-10 of some macrocyclic trichothecenes increases the activity. Conjugated trichothecenes could release their toxic precursors after hydrolysis in animals, and present an additional potential risk. The SAR study of trichothecenes should provide some crucial information for a better understanding of trichothecene chemical and biological properties in food contamination.

  11. Safety assessment of widely used fermented virgin coconut oil (Cocos nucifera) in Malaysia: Chronic toxicity studies and SAR analysis of the active components.

    Science.gov (United States)

    Ibrahim, Ahmad H; Khan, Md Shamsuddin Sultan; Al-Rawi, Sawsan S; Ahamed, Mohamed B Khadeer; Majid, Aman Shah Bin Abdul; Al-Suede, Fouad Saleih R; Ji, Dan; Majid, Amin Malik Shah Abdul

    2016-11-01

    Fermented Virgin Coconut Oil (FVCO) is widely used in the Southeast Asia as food and traditional medicine. The objective of the present study is the evaluation of chronic safety of the commercialized FVCO of Malaysia and other Southeast Asian countries. A single dose of 5000 mg/kg of FVCO was administered orally in rats (each group, n = 5) for the acute toxicity study and 175, 550 and 2000 mg/kg for sub-chronic and chronic studies (each group, n = 10), respectively. The behavior, mortality, and body weight of the rats were assessed to determine the toxic effects of FVCO. The haematology, biochemistry and histopathology of the treated rats were evaluated. The treated rats were safe with the dose of 5000 mg/kg in acute, sub-chronic and chronic indication. Abnormal clinical signs and morphology (gross necroscopy), changes of organ weight, anomalous haematology and biochemistry indexes were not found in comparison with the control (p > 0.05). In general, food and water intake were higher in the treated rats related to control. It was concluded that the presence of the antioxidant active compounds of FVCO might be the reason of safety. The structure activity relationship (SAR) provides a comprehensive mechanism to determine the safety that is the presence of the electron donating phenolic groups, carbonyl groups, and carboxylic acid in the ortho and meta position of the aromatic rings. The SAR showed the antioxidant properties of myristic acid and lauric acid determined by GC-MS analysis. This result suggests the safety of FVCO for chronic use, nutritional activity that FVCO formulation complies the requirements of regulatory agencies. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

    NARCIS (Netherlands)

    ter Meulen, Jan; Bakker, Alexander B. H.; van den Brink, Edward N.; Weverling, Gerrit J.; Martina, Byron E. E.; Haagmans, Bart L.; Kuiken, Thijs; de Kruif, John; Preiser, Wolfgang; Spaan, Willy; Gelderblom, Hans R.; Goudsmit, Jaap; Osterhaus, Albert D. M. E.

    2004-01-01

    SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal

  13. Use of SAR data for proliferation monitoring

    International Nuclear Information System (INIS)

    Lafitte, M.; Robin, J.P.

    2013-01-01

    Synthetic Aperture Radar (SAR) is an active and coherent system. SAR images are complex data which contain both amplitude and phase information. The analysis of single SAR data required a very good experience and a good understanding of SAR geometry regarding layover, shadowing, texture and speckle. Image analyst can depicts and describes most of the facilities related to nuclear proliferation and weapons of mass destruction (WMD). The Amplitude Change Detection (ACD) technique consists of a combination of two or three SAR amplitude data acquired with similar orbit and frequency parameters on different dates. That technique provides a very good overview of the changes and particularly regarding vehicles activity and constructions ongoing within the area of interest over the monitoring period. One of the particularities of the SAR systems is to be coherent. The phase of a single image is not exploitable. Thus when two or more SAR data have been acquired with identical orbit and frequency parameters, the phases shift are indicators of changes such as structural changes, terrain subsidence or motion. The Multi-Temporal Coherence (MTC) product merged the two type of information previously detailed: the ACD and coherence analysis. It consists of the combination of two amplitude images and the corresponding coherence computed image. The MTC image may highlights changes between two states of a target which on the ACD analysis appeared unchanged. EUSC uses the difference interferometry techniques in order to estimate volumes that have changed between two acquisition dates. The paper is followed by the slides of the presentation. (A.C.)

  14. Biological and structure-activity evaluation of chalcone derivatives against bacteria and fungi

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Wender A.; Andrade, Carlos Kleber Z.; Napolitano, Hamilton B., E-mail: wender@unb.br, E-mail: ckleber@unb.br [Universidade de Brasilia (LaQMOS/UnB), DF (Brazil). Inst. de Quimica; Vencato, Ivo; Castro, Miriam R.C. de; Camargo, Ademir J. [Universidade Estadual de Goias (UEG), Anapolis, GO (Brazil). Ciencias Exatas e Tecnologicas; Lariucci, Carlito [Universidade Estadual de Goias (UEG), Goiania, GO (Brazil). Inst. de Fisica

    2013-01-15

    The present work describes the antibacterial and antifungal activities of several chalcones obtained by a straight Claisen-Schmidt aldol condensation determined by the minimal inhibitory concentration against different microorganisms (Gram-positive and Gram-negative bacteria and fungi). Solid state crystal structures of seven chalcones were determined by X-ray diffraction (XRD) analysis. Chemometric studies were carried out in order to identify a potential structure activity relationship. (author)

  15. TerraSAR-X InSAR multipass analysis on Venice, Italy)

    Science.gov (United States)

    Nitti, D. O.; Nutricato, R.; Bovenga, F.; Refice, A.; Chiaradia, M. T.; Guerriero, L.

    2009-09-01

    The TerraSAR-X (copyright) mission, launched in 2007, carries a new X-band Synthetic Aperture Radar (SAR) sensor optimally suited for SAR interferometry (InSAR), thus allowing very promising application of InSAR techniques for the risk assessment on areas with hydrogeological instability and especially for multi-temporal analysis, such as Persistent Scatterer Interferometry (PSI) techniques, originally developed at Politecnico di Milano. The SPINUA (Stable Point INterferometry over Unurbanised Areas) technique is a PSI processing methodology which has originally been developed with the aim of detection and monitoring of coherent PS targets in non or scarcely-urbanized areas. The main goal of the present work is to describe successful applications of the SPINUA PSI technique in processing X-band data. Venice has been selected as test site since it is in favorable settings for PSI investigations (urban area containing many potential coherent targets such as buildings) and in view of the availability of a long temporal series of TerraSAR-X stripmap acquisitions (27 scenes in all). The Venice Lagoon is affected by land sinking phenomena, whose origins are both natural and man-induced. The subsidence of Venice has been intensively studied for decades by determining land displacements through traditional monitoring techniques (leveling and GPS) and, recently, by processing stacks of ERS/ENVISAT SAR data. The present work is focused on an independent assessment of application of PSI techniques to TerraSAR-X stripmap data for monitoring the stability of the Venice area. Thanks to its orbital repeat cycle of only 11 days, less than a third of ERS/ENVISAT C-band missions, the maximum displacement rate that can be unambiguously detected along the Line-of-Sight (LOS) with TerraSAR-X SAR data through PSI techniques is expected to be about twice the corresponding value of ESA C-band missions, being directly proportional to the sensor wavelength and inversely proportional to the

  16. Accelerated Scientific InSAR Processing, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Neva Ridge Technologies proposes to develop a suite of software tools for the analysis of SAR and InSAR data, focused on having a robust and adopted capability well...

  17. Simultaneous Observation Data of GB-SAR/PiSAR to Detect Flooding in an Urban Area

    Directory of Open Access Journals (Sweden)

    Manabu Watanabe

    2010-01-01

    Full Text Available We analyzed simultaneous observation data with ground-based synthetic aperture radar (GB-SAR and airborne SAR (PiSAR over a flood test site at which a simple house was constructed in a field. The PiSAR σ∘ under flood condition was 0.9 to 3.4 dB higher than that under nonflood condition. GB-SAR gives high spatial resolution as we could identify a single scattering component and a double bounce component from the house. GB-SAR showed that the σ∘ difference between the flooding and nonflooding conditions came from the double bounce scattering. We also confirm that the entropy is a sensitive parameter in the eigenvalue decomposition parameters, if the scattering process is dominated by the double bounce scattering. We conclude that σ∘ and entropy are a good parameter to be used to detect flooding, not only in agricultural and forest regions, but also in urban areas. We also conclude that GB-SAR is a powerful tool to supplement satellite and airborne observation, which has a relatively low spatial resolution.

  18. Simultaneous Observation Data of GB-SAR/PiSAR to Detect Flooding in an Urban Area

    Directory of Open Access Journals (Sweden)

    Shimada Masanobu

    2010-01-01

    Full Text Available Abstract We analyzed simultaneous observation data with ground-based synthetic aperture radar (GB-SAR and airborne SAR (PiSAR over a flood test site at which a simple house was constructed in a field. The PiSAR under flood condition was 0.9 to 3.4 dB higher than that under nonflood condition. GB-SAR gives high spatial resolution as we could identify a single scattering component and a double bounce component from the house. GB-SAR showed that the difference between the flooding and nonflooding conditions came from the double bounce scattering. We also confirm that the entropy is a sensitive parameter in the eigenvalue decomposition parameters, if the scattering process is dominated by the double bounce scattering. We conclude that and entropy are a good parameter to be used to detect flooding, not only in agricultural and forest regions, but also in urban areas. We also conclude that GB-SAR is a powerful tool to supplement satellite and airborne observation, which has a relatively low spatial resolution.

  19. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...... a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under...... the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

  20. Infrastructure monitoring with spaceborne SAR sensors

    CERN Document Server

    ANGHEL, ANDREI; CACOVEANU, REMUS

    2017-01-01

    This book presents a novel non-intrusive infrastructure monitoring technique based on the detection and tracking of scattering centers in spaceborne SAR images. The methodology essentially consists of refocusing each available SAR image on an imposed 3D point cloud associated to the envisaged infrastructure element and identifying the reliable scatterers to be monitored by means of four dimensional (4D) tomography. The methodology described in this book provides a new perspective on infrastructure monitoring with spaceborne SAR images, is based on a standalone processing chain, and brings innovative technical aspects relative to conventional approaches. The book is intended primarily for professionals and researchers working in the area of critical infrastructure monitoring by radar remote sensing.

  1. PRF Ambiguity Detrmination for Radarsat ScanSAR System

    Science.gov (United States)

    Jin, Michael Y.

    1998-01-01

    PRF ambiguity is a potential problem for a spaceborne SAR operated at high frequencies. For a strip mode SAR, there were several approaches to solve this problem. This paper, however, addresses PRF ambiguity determination algorithms suitable for a burst mode SAR system such as the Radarsat ScanSAR. The candidate algorithms include the wavelength diversity algorithm, range look cross correlation algorithm, and multi-PRF algorithm.

  2. SARS Risk Perception, Knowledge, Precautions, and Information Sources, the Netherlands

    Science.gov (United States)

    Aro, Arja R.; Oenema, Anke; de Zwart, Onno; Richardus, Jan Hendrik; Bishop, George D.

    2004-01-01

    Severe acute respiratory syndrome (SARS)–related risk perceptions, knowledge, precautionary actions, and information sources were studied in the Netherlands during the 2003 SARS outbreak. Although respondents were highly aware of the SARS outbreak, the outbreak did not result in unnecessary precautionary actions or fears. PMID:15496256

  3. Science data collection with polarimetric SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Woelders, Kim; Madsen, Søren Nørvang

    1996-01-01

    Discusses examples on the use of polarimetric SAR in a number of Earth science studies. The studies are presently being conducted by the Danish Center for Remote Sensing. A few studies of the European Space Agency's EMAC programme are also discussed. The Earth science objectives are presented......, and the potential of polarimetric SAR is discussed and illustrated with data collected by the Danish airborne EMISAR system during a number of experiments in 1994 and 1995. The presentation will include samples of data acquired for the different studies...

  4. Satellite sar detection of hurricane helene (2006)

    DEFF Research Database (Denmark)

    Ju, Lian; Cheng, Yongcun; Xu, Qing

    2013-01-01

    In this paper, the wind structure of hurricane Helene (2006) over the Atlantic Ocean is investigated from a C-band RADARSAT-1 synthetic aperture radar (SAR) image acquired on 20 September 2006. First, the characteristics, e.g., the center, scale and area of the hurricane eye (HE) are determined. ...... observations from the stepped frequency microwave radiometer (SFMR) on NOAA P3 aircraft. All the results show the capability of hurricane monitoring by satellite SAR. Copyright © 2013 by the International Society of Offshore and Polar Engineers (ISOPE)....

  5. The planned Alaska SAR Facility - An overview

    Science.gov (United States)

    Carsey, Frank; Weeks, Wilford

    1987-01-01

    The Alaska SAR Facility (ASF) is described in an overview fashion. The facility consists of three major components, a Receiving Ground System, a SAR Processing System and an Analysis and Archiving System; the ASF Program also has a Science Working Team and the requisite management and operations systems. The ASF is now an approved and fully funded activity; detailed requirements and science background are presented for the facility to be implemented for data from the European ERS-1, the Japanese ERS-1 and Radarsat.

  6. Geologic mapping in Greenland with polarimetric SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Madsen, Søren Nørvang; Brooks, C. K.

    1995-01-01

    The application of synthetic aperture radar (SAR) for geologic mapping in Greenland is investigated by the Danish Center for Remote Sensing (DCRS) in co-operation with the Danish Lithosphere Centre (DLC). In 1994 a pilot project was conducted in East Greenland. The Danish airborne SAR, EMISAR...... mapping is complicated by an extreme topography leading to massive shadowing, foreshortening and layover. An artifact characterised by high cross-polarisation is observed behind many sharp mountain ridges. A multi-reflection hypothesis has been investigated without finding the ultimate proof...

  7. SARS knowledge, perceptions, and behaviors: a comparison between Finns and the Dutch during the SARS outbreak in 2003

    NARCIS (Netherlands)

    Vartti, A.M.; Oenema, A.; Schreck, M.; Uutela, A.; Zwart, de O.; Brug, J.; Aro, A.R.

    2009-01-01

    BACKGROUND: The SARS outbreak served to test both local and international outbreak management and risk communication practices. PURPOSE: The study compares SARS knowledge, perceptions, behaviors, and information between Finns and the Dutch during the SARS outbreak in 2003. METHOD: The participants

  8. Design and realization of an active SAR calibrator for TerraSAR-X

    Science.gov (United States)

    Dummer, Georg; Lenz, Rainer; Lutz, Benjamin; Kühl, Markus; Müller-Glaser, Klaus D.; Wiesbeck, Werner

    2005-10-01

    TerraSAR-X is a new earth observing satellite which will be launched in spring 2006. It carries a high resolution X-band SAR sensor. For high image data quality, accurate ground calibration targets are necessary. This paper describes a novel system concept for an active and highly integrated, digitally controlled SAR system calibrator. A total of 16 active transponder and receiver systems and 17 receiver only systems will be fabricated for a calibration campaign. The calibration units serve for absolute radiometric calibration of the SAR image data. Additionally, they are equipped with an extra receiver path for two dimensional satellite antenna pattern recognition. The calibrator is controlled by a dedicated digital Electronic Control Unit (ECU). The different voltages needed by the calibrator and the ECU are provided by the third main unit called Power Management Unit (PMU).

  9. SAR Image Classification Based on Its Texture Features

    Institute of Scientific and Technical Information of China (English)

    LI Pingxiang; FANG Shenghui

    2003-01-01

    SAR images not only have the characteristics of all-ay, all-eather, but also provide object information which is different from visible and infrared sensors. However, SAR images have some faults, such as more speckles and fewer bands. The authors conducted the experiments of texture statistics analysis on SAR image features in order to improve the accuracy of SAR image interpretation.It is found that the texture analysis is an effective method for improving the accuracy of the SAR image interpretation.

  10. Diazo Reagents with Small Steric Footprints for Simultaneous Arming/SAR Studies of Alcohol-Containing Natural Products via O–H Insertion

    Science.gov (United States)

    Chamni, Supakarn; He, Qing-Li; Dang, Yongjun; Bhat, Shridhar; Liu, Jun O.; Romo, Daniel

    2011-01-01

    Natural products are essential tools for basic cellular studies leading to the identification of medically relevant protein targets and the discovery of potential therapeutic leads. The development of methods that enable mild and selective derivatization of natural products continues to be of significant interest for mining their information-rich content. Herein, we describe novel diazo reagents for simultaneous arming and structure-activity relationship (SAR) studies of alcohol-containing natural products with a small steric footprint, namely an α-trifluoroethyl (HTFB) substituted reagent. The Rh(II)-catalyzed O–H insertion reaction of several natural products, including the potent translation inhibitor lactimidomycin, was investigated and useful reactivity and both chemo- and site (chemosite) selectivities were observed. Differential binding to the known protein targets of both FK506 and fumagillol was demonstrated, validating the advantage of the smaller steric footprint of trifluoroethyl derivatives. A p-azidophenyl diazo reagent is also described that will prove useful for photoaffinity labeling of low affinity small molecule protein receptors. PMID:21894934

  11. Case studies to test: A framework for using structural, reactivity, metabolic and physicochemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments.

    Science.gov (United States)

    Blackburn, Karen; Bjerke, Donald; Daston, George; Felter, Susan; Mahony, Catherine; Naciff, Jorge; Robison, Steven; Wu, Shengde

    2011-06-01

    A process for evaluating analogs for use in SAR (Structure-Activity Relationship) assessments was previously published (Wu et al. 2010). Subsequently, this process has been updated to include a decision tree for estrogen binding (from US EPA) and flags for developmental and reproductive toxicity (DART). This paper presents the results of blinded case studies designed to test this updated framework. The results of these case studies support the conclusion that the process outlined by Wu et al. (2010) can be successfully applied to develop surrogate values for risk assessment. The read across results generated by the process were shown to be protective when compared to the actual toxicity data. Successful application of the approach requires significant expertise as well as discipline to not overstep the boundaries of the defined analogs and the rating system. The end result of this rigor can be the inability to read across all endpoints for all chemicals resulting in data gaps that cannot be filled using read across, however, this reflects the current state of the science and is preferable to making non-protective decisions. Future work will be targeted towards expanding read across capabilities. Two examples of a broader category approach are also shown. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Discovery, SAR, and Radiolabeling of Halogenated Benzimidazole Carboxamide Antagonists as Useful Tools for (alpha)4(beta)1 Integrin Expressed on T- and B-cell Lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, R D; Natarajan, A; Lau, E Y; Andrei, M; Solano, D M; Lightstone, F C; DeNardo, S J; Lam, K S; Kurth, M J

    2010-02-08

    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin is an attractive yet poorly understood target for selective diagnosis and treatment of T- and B-cell lymphomas. This report focuses on the rapid microwave preparation of medicinally pertinent benzimidazole heterocycles, structure-activity relationships (SAR) of novel halobenzimidazole carboxamide antagonists 3-6, and preliminary biological evaluation of radioiodinated agents 7, 8, and 18. The I-125 derivative 18 had good tumor uptake (12 {+-} 1% ID/g at 24 h; 4.5 {+-} 1% ID/g at 48 h) and tumor:kidney ratio ({approx}4:1 at 24 h; 2.5:1 at 48 h) in xenograft murine models of B-cell lymphoma. Molecular homology models of {alpha}{sub 4}{beta}{sub 1} integrin have predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. These high affinity ({approx} pM binding) halogenated ligands are attractive tools for medicinal and biological use; the fluoro and iodo derivatives are potential radiodiagnostic ({sup 18}F) or radiotherapeutic ({sup 131}I) agents, whereas the chloro and bromo analogues could provide structural insight into integrin-ligand interactions through photoaffinity cross-linking/mass spectroscopy experiments, as well as co-crystallization X-ray studies.

  13. CFAR Edge Detector for Polarimetric SAR Images

    DEFF Research Database (Denmark)

    Schou, Jesper; Skriver, Henning; Nielsen, Allan Aasbjerg

    2003-01-01

    Finding the edges between different regions in an image is one of the fundamental steps of image analysis, and several edge detectors suitable for the special statistics of synthetic aperture radar (SAR) intensity images have previously been developed. In this paper, a new edge detector for polar...

  14. Discovery and SAR of hydantoin TACE inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wensheng; Guo, Zhuyan; Orth, Peter; Madison, Vincent; Chen, Lei; Dai, Chaoyang; Feltz, Robert J.; Girijavallabhan, Vinay M.; Kim, Seong Heon; Kozlowski, Joseph A.; Lavey, Brian J.; Li, Dansu; Lundell, Daniel; Niu, Xiaoda; Piwinski, John J.; Popovici-Muller, Janeta; Rizvi, Razia; Rosner, Kristin E.; Shankar, Bandarpalle B.; Shih, Neng-Yang; Siddiqui, M.A.; Sun, J.; Tong, L.; Umland, S.; Wong, M.K.; Yang, D.Y.; Zhou, G. (Merck)

    2010-09-03

    We disclose inhibitors of TNF-{alpha} converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.

  15. Relevant Scatterers Characterization in SAR Images

    Science.gov (United States)

    Chaabouni, Houda; Datcu, Mihai

    2006-11-01

    Recognizing scenes in a single look meter resolution Synthetic Aperture Radar (SAR) images, requires the capability to identify relevant signal signatures in condition of variable image acquisition geometry, arbitrary objects poses and configurations. Among the methods to detect relevant scatterers in SAR images, we can mention the internal coherence. The SAR spectrum splitted in azimuth generates a series of images which preserve high coherence only for particular object scattering. The detection of relevant scatterers can be done by correlation study or Independent Component Analysis (ICA) methods. The present article deals with the state of the art for SAR internal correlation analysis and proposes further extensions using elements of inference based on information theory applied to complex valued signals. The set of azimuth looks images is analyzed using mutual information measures and an equivalent channel capacity is derived. The localization of the "target" requires analysis in a small image window, thus resulting in imprecise estimation of the second order statistics of the signal. For a better precision, a Hausdorff measure is introduced. The method is applied to detect and characterize relevant objects in urban areas.

  16. Digital demodulator for wide bandwidth SAR

    DEFF Research Database (Denmark)

    Jørgensen, Jørn Hjelm

    2000-01-01

    A novel approach to the design of efficient digital quadrature demodulators for wide bandwidth SAR systems is described. Efficiency is obtained by setting the intermediate frequency to 1/4 the ADC sampling frequency. One channel is made filter-free by synchronizing the local oscillator...

  17. Offshore wind mapping Mediterranean area using SAR

    DEFF Research Database (Denmark)

    Calaudi, Rosamaria; Arena, Felice; Badger, Merete

    2013-01-01

    Satellite observations of the ocean surface, for example from Synthetic Aperture Radars (SAR), provide information about the spatial wind variability over large areas. This is of special interest in the Mediterranean Sea, where spatial wind information is only provided by sparse buoys, often with...

  18. Peptide Mimicrying Between SARS Coronavirus Spike Protein and Human Proteins Reacts with SARS Patient Serum

    Directory of Open Access Journals (Sweden)

    K.-Y. Hwa

    2008-01-01

    Full Text Available Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV. The spike (S protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927–937 and D08 (residues 942–951 were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490–502 stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.

  19. The Seamless SAR Archive (SSARA) Project and Other SAR Activities at UNAVCO

    Science.gov (United States)

    Baker, S.; Crosby, C. J.; Meertens, C. M.; Fielding, E. J.; Bryson, G.; Buechler, B.; Nicoll, J.; Baru, C.

    2014-12-01

    The seamless synthetic aperture radar archive (SSARA) implements a seamless distributed access system for SAR data and derived data products (i.e. interferograms). SSARA provides a unified application programming interface (API) for SAR data search and results at the Alaska Satellite Facility and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives. Interest from the international community has prompted an effort to incorporate ESA's Virtual Archive 4 Geohazard Supersites and Natural Laboratories (GSNL) collections and other archives into the federated query service. SSARA also provides Digital Elevation Model access for topographic correction via a simple web service through OpenTopography and tropospheric correction products through JPL's OSCAR service. Additionally, UNAVCO provides data storage capabilities for WInSAR PIs with approved TerraSAR-X and ALOS-2 proposals which allows easier distribution to US collaborators on associated proposals and facilitates data access through the SSARA web services. Further work is underway to incorporate federated data discovery for GSNL across SAR, GPS, and seismic datasets provided by web services from SSARA, GSAC, and COOPEUS.

  20. Spaceborne Differential SAR Interferometry: Data Analysis Tools for Deformation Measurement

    Directory of Open Access Journals (Sweden)

    Michele Crosetto

    2011-02-01

    Full Text Available This paper is focused on spaceborne Differential Interferometric SAR (DInSAR for land deformation measurement and monitoring. In the last two decades several DInSAR data analysis procedures have been proposed. The objective of this paper is to describe the DInSAR data processing and analysis tools developed at the Institute of Geomatics in almost ten years of research activities. Four main DInSAR analysis procedures are described, which range from the standard DInSAR analysis based on a single interferogram to more advanced Persistent Scatterer Interferometry (PSI approaches. These different procedures guarantee a sufficient flexibility in DInSAR data processing. In order to provide a technical insight into these analysis procedures, a whole section discusses their main data processing and analysis steps, especially those needed in PSI analyses. A specific section is devoted to the core of our PSI analysis tools: the so-called 2+1D phase unwrapping procedure, which couples a 2D phase unwrapping, performed interferogram-wise, with a kind of 1D phase unwrapping along time, performed pixel-wise. In the last part of the paper, some examples of DInSAR results are discussed, which were derived by standard DInSAR or PSI analyses. Most of these results were derived from X-band SAR data coming from the TerraSAR-X and CosmoSkyMed sensors.

  1. SAR Raw Data Generation for Complex Airport Scenes

    Directory of Open Access Journals (Sweden)

    Jia Li

    2014-10-01

    Full Text Available The method of generating the SAR raw data of complex airport scenes is studied in this paper. A formulation of the SAR raw signal model of airport scenes is given. Via generating the echoes from the background, aircrafts and buildings, respectively, the SAR raw data of the unified SAR imaging geometry is obtained from their vector additions. The multipath scattering and the shadowing between the background and different ground covers of standing airplanes and buildings are analyzed. Based on the scattering characteristics, coupling scattering models and SAR raw data models of different targets are given, respectively. A procedure is given to generate the SAR raw data of airport scenes. The SAR images from the simulated raw data demonstrate the validity of the proposed method.

  2. ANALYSIS OF MULTIPATH PIXELS IN SAR IMAGES

    Directory of Open Access Journals (Sweden)

    J. W. Zhao

    2016-06-01

    Full Text Available As the received radar signal is the sum of signal contributions overlaid in one single pixel regardless of the travel path, the multipath effect should be seriously tackled as the multiple bounce returns are added to direct scatter echoes which leads to ghost scatters. Most of the existing solution towards the multipath is to recover the signal propagation path. To facilitate the signal propagation simulation process, plenty of aspects such as sensor parameters, the geometry of the objects (shape, location, orientation, mutual position between adjacent buildings and the physical parameters of the surface (roughness, correlation length, permittivitywhich determine the strength of radar signal backscattered to the SAR sensor should be given in previous. However, it's not practical to obtain the highly detailed object model in unfamiliar area by field survey as it's a laborious work and time-consuming. In this paper, SAR imaging simulation based on RaySAR is conducted at first aiming at basic understanding of multipath effects and for further comparison. Besides of the pre-imaging simulation, the product of the after-imaging, which refers to radar images is also taken into consideration. Both Cosmo-SkyMed ascending and descending SAR images of Lupu Bridge in Shanghai are used for the experiment. As a result, the reflectivity map and signal distribution map of different bounce level are simulated and validated by 3D real model. The statistic indexes such as the phase stability, mean amplitude, amplitude dispersion, coherence and mean-sigma ratio in case of layover are analyzed with combination of the RaySAR output.

  3. New challenges for a SAR toolbox

    International Nuclear Information System (INIS)

    Loreaux, P.; Quin, G.

    2013-01-01

    High resolution multi-frequency synthetic aperture radar (SAR) imagery, available since early 2008, brings all weather capability and day/night operability in support of safeguards verification. Today, a combined approach of high resolution optical and radar imagery in monitoring exercise would enable looking at any area of interest on daily basis. One of the challenges is the co-registration of SAR images acquired with different acquisition mode and also with different optical images. We show in this paper the on-going research work to find a general co-register method and an automatic tool to detect changes. Before having an operational co-register tool, a method to find automatically tie points between SAR images acquired with different acquisition mode and with optical images has to be developed. Concerning an automatic change detection method we can conclude that the study of the Harmonic mean, Geometric mean and Arithmetic mean, enables several applications like change detection for SAR imagery. Thus, we developed the MAGMA (Method for Arithmetic and Geometric Means Analysis) change detection method. As shown in this paper, the MAGMA method improves the Maximum Likelihood techniques like GLRT, using Information-Theory concepts to detect changes between SAR amplitude images. The major improvement consists in a lower false detection rate, especially in low amplitude areas. The second improvement consists in a better location of the changes in clearly delimited areas, which enables precise interpretations. Results presented here reveal the potential of high resolution radar imagery for a baseline description of some sites, change detection based on repeat pass imagery acquisitions and site specific constraints in coherent change detection due to cover conditions. (A.C.)

  4. A Ligand Structure-Activity Study of DNA-Based Catalytic Asymmetric Hydration and Diels-Alder Reactions

    NARCIS (Netherlands)

    Rosati, F.; Roelfes, J.G.

    A structure-activity relationship study of the first generation ligands for the DNA-based asymmetric hydration of enones and Diels-Alder reaction in water is reported. The design of the ligand was optimized resulting in a maximum ee of 83% in the hydration reaction and 75% in the Diels-Alder

  5. Characterizing and estimating noise in InSAR and InSAR time series with MODIS

    Science.gov (United States)

    Barnhart, William D.; Lohman, Rowena B.

    2013-01-01

    InSAR time series analysis is increasingly used to image subcentimeter displacement rates of the ground surface. The precision of InSAR observations is often affected by several noise sources, including spatially correlated noise from the turbulent atmosphere. Under ideal scenarios, InSAR time series techniques can substantially mitigate these effects; however, in practice the temporal distribution of InSAR acquisitions over much of the world exhibit seasonal biases, long temporal gaps, and insufficient acquisitions to confidently obtain the precisions desired for tectonic research. Here, we introduce a technique for constraining the magnitude of errors expected from atmospheric phase delays on the ground displacement rates inferred from an InSAR time series using independent observations of precipitable water vapor from MODIS. We implement a Monte Carlo error estimation technique based on multiple (100+) MODIS-based time series that sample date ranges close to the acquisitions times of the available SAR imagery. This stochastic approach allows evaluation of the significance of signals present in the final time series product, in particular their correlation with topography and seasonality. We find that topographically correlated noise in individual interferograms is not spatially stationary, even over short-spatial scales (<10 km). Overall, MODIS-inferred displacements and velocities exhibit errors of similar magnitude to the variability within an InSAR time series. We examine the MODIS-based confidence bounds in regions with a range of inferred displacement rates, and find we are capable of resolving velocities as low as 1.5 mm/yr with uncertainties increasing to ∼6 mm/yr in regions with higher topographic relief.

  6. FDTD calculation of whole-body average SAR in adult and child models for frequencies from 30 MHz to 3 GHz

    International Nuclear Information System (INIS)

    Wang Jianqing; Fujiwara, Osamu; Kodera, Sachiko; Watanabe, Soichi

    2006-01-01

    Due to the difficulty of the specific absorption rate (SAR) measurement in an actual human body for electromagnetic radio-frequency (RF) exposure, in various compliance assessment procedures the incident electric field or power density is being used as a reference level, which should never yield a larger whole-body average SAR than the basic safety limit. The relationship between the reference level and the whole-body average SAR, however, was established mainly based on numerical calculations for highly simplified human modelling dozens of years ago. Its validity is being questioned by the latest calculation results. In verifying the validity of the reference level with respect to the basic SAR limit for RF exposure, it is essential to have a high accuracy of human modelling and numerical code. In this study, we made a detailed error analysis in the whole-body average SAR calculation for the finite-difference time-domain (FDTD) method in conjunction with the perfectly matched layer (PML) absorbing boundaries. We derived a basic rule for the PML employment based on a dielectric sphere and the Mie theory solution. We then attempted to clarify to what extent the whole-body average SAR may reach using an anatomically based Japanese adult model and a scaled child model. The results show that the whole-body average SAR under the ICNIRP reference level exceeds the basic safety limit nearly 30% for the child model both in the resonance frequency and 2 GHz band

  7. FDTD calculation of whole-body average SAR in adult and child models for frequencies from 30 MHz to 3 GHz

    Energy Technology Data Exchange (ETDEWEB)

    Wang Jianqing [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Fujiwara, Osamu [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Kodera, Sachiko [Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Watanabe, Soichi [National Institute of Information and Communications Technology, Nukui-kitamachi, Koganei, Tokyo 184-8795 (Japan)

    2006-09-07

    Due to the difficulty of the specific absorption rate (SAR) measurement in an actual human body for electromagnetic radio-frequency (RF) exposure, in various compliance assessment procedures the incident electric field or power density is being used as a reference level, which should never yield a larger whole-body average SAR than the basic safety limit. The relationship between the reference level and the whole-body average SAR, however, was established mainly based on numerical calculations for highly simplified human modelling dozens of years ago. Its validity is being questioned by the latest calculation results. In verifying the validity of the reference level with respect to the basic SAR limit for RF exposure, it is essential to have a high accuracy of human modelling and numerical code. In this study, we made a detailed error analysis in the whole-body average SAR calculation for the finite-difference time-domain (FDTD) method in conjunction with the perfectly matched layer (PML) absorbing boundaries. We derived a basic rule for the PML employment based on a dielectric sphere and the Mie theory solution. We then attempted to clarify to what extent the whole-body average SAR may reach using an anatomically based Japanese adult model and a scaled child model. The results show that the whole-body average SAR under the ICNIRP reference level exceeds the basic safety limit nearly 30% for the child model both in the resonance frequency and 2 GHz band.

  8. Low cost realization of space-borne synthectic aperture radar - MicroSAR

    Science.gov (United States)

    Carter, D.; Hall, C.

    Spaceborne Earth Observation data has been used for decades in the areas of meteorology and optical imaging. The systems and satellites have, in the main, been owned and operated by a few government institutions and agencies. More recently industrial organizations in North America have joined the list. Few of these, however, include Synthetic Aperture Radar (SAR)., although the additional utility in terms of all weather, 24 hour measurement capability over the Earth's surface is well recognized. Three major factors explain this:1) Relationships between the SAR measurements of radar backscatter and images to the specific information needs have not been seen as sufficiently well understood or robust2) Availability of suitable sources, at the relevant performance and data quality have been inadequate to provide service assurance that is necessary to sustain commercial businesses3) Costs associated with building, launching and operating spaceborne SAR have not been low enough as to achieve an acceptable return of investment. A significant amount of research and development has been undertaken throughout the World to establish reliable and robust algorithms for information extraction from SAR data. Much of this work has been carried out utilizing airborne systems over localized and carefully controlled regions. In addition, an increasing number of pilot services have been offered by geo-information providers. This has allowed customer confidence to grow. With the status of spaceborne SAR being effectively in the development phase, commercial funding has been scarce, and there has been need to rely on government and institutional budgets. Today the increasing maturity of the technology of SAR and its applications is beginning to attract the commercial sector. This is the funding necessary to realize sufficient assets to be able to provide a robust supply of SAR data to the geo-information providers and subsequently a reliable service to customers. Reducing the costs

  9. Tracking morphological changes and slope instability using spaceborne and ground-based SAR data

    Science.gov (United States)

    Di Traglia, Federico; Nolesini, Teresa; Ciampalini, Andrea; Solari, Lorenzo; Frodella, William; Bellotti, Fernando; Fumagalli, Alfio; De Rosa, Giuseppe; Casagli, Nicola

    2018-01-01

    Stromboli (Aeolian Archipelago, Italy) is an active volcano that is frequently affected by moderate to large mass wasting, which has occasionally triggered tsunamis. With the aim of understanding the relationship between the geomorphologic evolution and slope instability of Stromboli, remote sensing information from space-born Synthetic Aperture Radar (SAR) change detection and interferometry (InSAR) () and Ground Based InSAR (GBInSAR) was compared with field observations and morphological analyses. Ground reflectivity and SqueeSAR™ (an InSAR algorithm for surface deformation monitoring) displacement measurements from X-band COSMO-SkyMed satellites (CSK) were analysed together with displacement measurements from a permanent-sited, Ku-band GBInSAR system. Remote sensing results were compared with a preliminary morphological analysis of the Sciara del Fuoco (SdF) steep volcanic flank, which was carried out using a high-resolution Digital Elevation Model (DEM). Finally, field observations, supported by infrared thermographic surveys (IRT), allowed the interpretation and validation of remote sensing data. The analysis of the entire dataset (collected between January 2010 and December 2014) covers a period characterized by a low intensity of Strombolian activity. This period was punctuated by the occurrence of lava overflows, occurring from the crater terrace evolving downslope toward SdF, and flank eruptions, such as the 2014 event. The amplitude of the CSK images collected between February 22nd, 2010, and December 18th, 2014, highlights that during periods characterized by low-intensity Strombolian activity, the production of materials ejected from the crater terrace towards the SdF is generally low, and erosion is the prevailing process mainly affecting the central sector of the SdF. CSK-SqueeSAR™ and GBInSAR data allowed the identification of low displacements in the SdF, except for high displacement rates (up to 1.5 mm/h) that were measured following both lava

  10. Spaceborne Polarimetric SAR Interferometry: Performance Analysis and Mission Concepts

    Directory of Open Access Journals (Sweden)

    Shane R. Cloude

    2005-12-01

    Full Text Available We investigate multichannel imaging radar systems employing coherent combinations of polarimetry and interferometry (Pol-InSAR. Such systems are well suited for the extraction of bio- and geophysical parameters by evaluating the combined scattering from surfaces and volumes. This combination leads to several important differences between the design of Pol-InSAR sensors and conventional single polarisation SAR interferometers. We first highlight these differences and then investigate the Pol-InSAR performance of two proposed spaceborne SAR systems (ALOS/PalSAR and TerraSAR-L operating in repeat-pass mode. For this, we introduce the novel concept of a phase tube which enables (1 a quantitative assessment of the Pol-InSAR performance, (2 a comparison between different sensor configurations, and (3 an optimization of the instrument settings for different Pol-InSAR applications. The phase tube may hence serve as an interface between system engineers and application-oriented scientists. The performance analysis reveals major limitations for even moderate levels of temporal decorrelation. Such deteriorations may be avoided in single-pass sensor configurations and we demonstrate the potential benefits from the use of future bi- and multistatic SAR interferometers.

  11. Federated query services provided by the Seamless SAR Archive project

    Science.gov (United States)

    Baker, S.; Bryson, G.; Buechler, B.; Meertens, C. M.; Crosby, C. J.; Fielding, E. J.; Nicoll, J.; Youn, C.; Baru, C.

    2013-12-01

    The NASA Advancing Collaborative Connections for Earth System Science (ACCESS) seamless synthetic aperture radar (SAR) archive (SSARA) project is a 2-year collaboration between UNAVCO, the Alaska Satellite Facility (ASF), the Jet Propulsion Laboratory (JPL), and OpenTopography at the San Diego Supercomputer Center (SDSC) to design and implement a seamless distributed access system for SAR data and derived data products (i.e. interferograms). A major milestone for the first year of the SSARA project was a unified application programming interface (API) for SAR data search and results at ASF and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives (http://www.unavco.org/ws/brokered/ssara/sar/search). A command line client that utilizes this new service is provided as an open source utility for the community on GitHub (https://github.com/bakerunavco/SSARA). Further API development and enhancements added more InSAR specific keywords and quality control parameters (Doppler centroid, faraday rotation, InSAR stack size, and perpendicular baselines). To facilitate InSAR processing, the federated query service incorporated URLs for DEM (from OpenTopography) and tropospheric corrections (from the JPL OSCAR service) in addition to the URLs for SAR data. This federated query service will provide relevant QC metadata for selecting pairs of SAR data for InSAR processing and all the URLs necessary for interferogram generation. Interest from the international community has prompted an effort to incorporate other SAR data archives (the ESA Virtual Archive 4 and the DLR TerraSAR-X_SSC Geohazard Supersites and Natural Laboratories collections) into the federated query service which provide data for researchers outside the US and North America.

  12. Pasture Monitoring Using SAR with COSMO-SkyMed, ENVISAT ASAR, and ALOS PALSAR in Otway, Australia

    Directory of Open Access Journals (Sweden)

    Xiaojing Li

    2013-07-01

    Full Text Available Because of all-weather working ability, sensitivity to biomass and moisture, and high spatial resolution, Synthetic aperture radar (SAR satellite images can perfectly complement optical images for pasture monitoring. This paper aims to examine the potential of the integration of COnstellation of small Satellites for the Mediterranean basin Observasion (COSMO-SkyMed, Environmental Satellite Advanced Synthetic Aperture Radar (ENVISAT ASAR, and Advanced Land Observing Satellite Phased Array type L-band Synthetic Aperture Radar (ALOS PALSAR radar signals at horizontally emitted and received polarization (HH for pasture monitoring at the paddock scale in order to guide farmers for better management. The pasture site is selected, in Otway, Victoria, Australia. The biomass, water content of grass, and soil moisture over this site were analyzed with these three bands of SAR images, through linear relationship between SAR backscattering coefficient, and vegetation indices Normalized Differential Vegetation Index (NDVI, Normalized Difference Water Index (NDWI, Enhanced Vegetation Index (EVI, together with soil moisture index (MI. NDVI, NDWI, and MI are considered as proxy of pasture biomass, plant water content, and soil moisture, respectively, and computed from optical images and climate data. SAR backscattering coefficient and vegetation indices are computed within a grass zone, defined by classification with MODIS data. The grass condition and grazing activities for specific paddocks are detectable, based on SAR backscatter, with all three wavelengths datasets. Both temporal and spatial analysis results show that the X-band SAR has the highest correlation to the vegetation indices. However, its accuracy can be affected by wet weather due to its sensitivity to the water on leaves. The C-band HH backscattering coefficient showed moderate reliability to evaluate biomass and water content of grass, with limited influence from rainfall in the dry season

  13. The estimation of 3D SAR distributions in the human head from mobile phone compliance testing data for epidemiological studies

    International Nuclear Information System (INIS)

    Wake, Kanako; Watanabe, Soichi; Taki, Masao; Varsier, Nadege; Wiart, Joe; Mann, Simon; Deltour, Isabelle; Cardis, Elisabeth

    2009-01-01

    A worldwide epidemiological study called 'INTERPHONE' has been conducted to estimate the hypothetical relationship between brain tumors and mobile phone use. In this study, we proposed a method to estimate 3D distribution of the specific absorption rate (SAR) in the human head due to mobile phone use to provide the exposure gradient for epidemiological studies. 3D SAR distributions due to exposure to an electromagnetic field from mobile phones are estimated from mobile phone compliance testing data for actual devices. The data for compliance testing are measured only on the surface in the region near the device and in a small 3D region around the maximum on the surface in a homogeneous phantom with a specific shape. The method includes an interpolation/extrapolation and a head shape conversion. With the interpolation/extrapolation, SAR distributions in the whole head are estimated from the limited measured data. 3D SAR distributions in the numerical head models, where the tumor location is identified in the epidemiological studies, are obtained from measured SAR data with the head shape conversion by projection. Validation of the proposed method was performed experimentally and numerically. It was confirmed that the proposed method provided good estimation of 3D SAR distribution in the head, especially in the brain, which is the tissue of major interest in epidemiological studies. We conclude that it is possible to estimate 3D SAR distributions in a realistic head model from the data obtained by compliance testing measurements to provide a measure for the exposure gradient in specific locations of the brain for the purpose of exposure assessment in epidemiological studies. The proposed method has been used in several studies in the INTERPHONE.

  14. Estimating the Doppler centroid of SAR data

    DEFF Research Database (Denmark)

    Madsen, Søren Nørvang

    1989-01-01

    attractive properties. An evaluation based on an existing SEASAT processor is reported. The time-domain algorithms are shown to be extremely efficient with respect to requirements on calculations and memory, and hence they are well suited to real-time systems where the Doppler estimation is based on raw SAR......After reviewing frequency-domain techniques for estimating the Doppler centroid of synthetic-aperture radar (SAR) data, the author describes a time-domain method and highlights its advantages. In particular, a nonlinear time-domain algorithm called the sign-Doppler estimator (SDE) is shown to have...... data. For offline processors where the Doppler estimation is performed on processed data, which removes the problem of partial coverage of bright targets, the ΔE estimator and the CDE (correlation Doppler estimator) algorithm give similar performance. However, for nonhomogeneous scenes it is found...

  15. PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

    Directory of Open Access Journals (Sweden)

    Kazi Abdus Salam

    2014-04-01

    Full Text Available The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3 is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1 on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1 against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.

  16. SAR Target Recognition via Supervised Discriminative Dictionary Learning and Sparse Representation of the SAR-HOG Feature

    Directory of Open Access Journals (Sweden)

    Shengli Song

    2016-08-01

    Full Text Available Automatic target recognition (ATR in synthetic aperture radar (SAR images plays an important role in both national defense and civil applications. Although many methods have been proposed, SAR ATR is still very challenging due to the complex application environment. Feature extraction and classification are key points in SAR ATR. In this paper, we first design a novel feature, which is a histogram of oriented gradients (HOG-like feature for SAR ATR (called SAR-HOG. Then, we propose a supervised discriminative dictionary learning (SDDL method to learn a discriminative dictionary for SAR ATR and propose a strategy to simplify the optimization problem. Finally, we propose a SAR ATR classifier based on SDDL and sparse representation (called SDDLSR, in which both the reconstruction error and the classification error are considered. Extensive experiments are performed on the MSTAR database under standard operating conditions and extended operating conditions. The experimental results show that SAR-HOG can reliably capture the structures of targets in SAR images, and SDDL can further capture subtle differences among the different classes. By virtue of the SAR-HOG feature and SDDLSR, the proposed method achieves the state-of-the-art performance on MSTAR database. Especially for the extended operating conditions (EOC scenario “Training 17 ∘ —Testing 45 ∘ ”, the proposed method improves remarkably with respect to the previous works.

  17. SAR Product Improvements and Enhancements - SARprises

    Science.gov (United States)

    2013-09-30

    paper on current fields at Orkney, Scotland, was accepted for publication in IEEE - TGARS and is currently in press (available on IEEE Xplore as Early...Sea surface velocity vector retrieval using dual-beam interferometry: First demonstration, IEEE TGARS, 43, 2494- 2502, 2005. [2] Chapron, B., F...Bight by airborne along-track interferometric SAR, Proc. IGARSS 2002, 1822-1824, IEEE , 2002. [4] Bjerklie, D.M., S.L. Dingman, C.J. Vorosmarty, C.H

  18. The Radiometric Measurement Quantity for SAR Images

    OpenAIRE

    Döring, Björn J.; Schwerdt, Marco

    2013-01-01

    A Synthetic Aperture Radar (SAR) system measures among other quantities the terrain radar reflectivity. After image calibration, the pixel intensities are commonly expressed in terms of radar cross sections (for point targets) or as backscatter coefficients (for distributed targets), which are directly related. This paper argues that pixel intensities are not generally proportional to radar cross section or derived physical quantities. The paper further proposes to replace the inaccurate term...

  19. Atmospheric Phase Delay in Sentinel SAR Interferometry

    Science.gov (United States)

    Krishnakumar, V.; Monserrat, O.; Crosetto, M.; Crippa, B.

    2018-04-01

    The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR) Interferometry (InSAR) has been a widely used geodetic technique for observing the Earth's surface, especially for mapping the Earth's topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth's atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere) are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC) of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR). To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET) and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC) images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate height and deformation

  20. ATMOSPHERIC PHASE DELAY IN SENTINEL SAR INTERFEROMETRY

    Directory of Open Access Journals (Sweden)

    V. Krishnakumar

    2018-04-01

    Full Text Available The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR Interferometry (InSAR has been a widely used geodetic technique for observing the Earth’s surface, especially for mapping the Earth’s topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth’s atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR. To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate

  1. Multiplier-free filters for wideband SAR

    DEFF Research Database (Denmark)

    Dall, Jørgen; Christensen, Erik Lintz

    2001-01-01

    This paper derives a set of parameters to be optimized when designing filters for digital demodulation and range prefiltering in SAR systems. Aiming at an implementation in field programmable gate arrays (FPGAs), an approach for the design of multiplier-free filters is outlined. Design results...... are presented in terms of filter complexity and performance. One filter has been coded in VHDL and preliminary results indicate that the filter can meet a 2 GHz input sample rate....

  2. Locating and defining underground goaf caused by coal mining from space-borne SAR interferometry

    Science.gov (United States)

    Yang, Zefa; Li, Zhiwei; Zhu, Jianjun; Yi, Huiwei; Feng, Guangcai; Hu, Jun; Wu, Lixin; Preusse, Alex; Wang, Yunjia; Papst, Markus

    2018-01-01

    It is crucial to locate underground goafs (i.e., mined-out areas) resulting from coal mining and define their spatial dimensions for effectively controlling the induced damages and geohazards. Traditional geophysical techniques for locating and defining underground goafs, however, are ground-based, labour-consuming and costly. This paper presents a novel space-based method for locating and defining the underground goaf caused by coal extraction using Interferometric Synthetic Aperture Radar (InSAR) techniques. As the coal mining-induced goaf is often a cuboid-shaped void and eight critical geometric parameters (i.e., length, width, height, inclined angle, azimuth angle, mining depth, and two central geodetic coordinates) are capable of locating and defining this underground space, the proposed method reduces to determine the eight geometric parameters from InSAR observations. Therefore, it first applies the Probability Integral Method (PIM), a widely used model for mining-induced deformation prediction, to construct a functional relationship between the eight geometric parameters and the InSAR-derived surface deformation. Next, the method estimates these geometric parameters from the InSAR-derived deformation observations using a hybrid simulated annealing and genetic algorithm. Finally, the proposed method was tested with both simulated and two real data sets. The results demonstrate that the estimated geometric parameters of the goafs are accurate and compatible overall, with averaged relative errors of approximately 2.1% and 8.1% being observed for the simulated and the real data experiments, respectively. Owing to the advantages of the InSAR observations, the proposed method provides a non-contact, convenient and practical method for economically locating and defining underground goafs in a large spatial area from space.

  3. Feature-Based Nonlocal Polarimetric SAR Filtering

    Directory of Open Access Journals (Sweden)

    Xiaoli Xing

    2017-10-01

    Full Text Available Polarimetric synthetic aperture radar (PolSAR images are inherently contaminated by multiplicative speckle noise, which complicates the image interpretation and image analyses. To reduce the speckle effect, several adaptive speckle filters have been developed based on the weighted average of the similarity measures commonly depending on the model or probability distribution, which are often affected by the distribution parameters and modeling texture components. In this paper, a novel filtering method introduces the coefficient of variance ( CV and Pauli basis (PB to measure the similarity, and the two features are combined with the framework of the nonlocal mean filtering. The CV is used to describe the complexity of various scenes and distinguish the scene heterogeneity; moreover, the Pauli basis is able to express the polarimetric information in PolSAR image processing. This proposed filtering combines the CV and Pauli basis to improve the estimation accuracy of the similarity weights. Then, the similarity of the features is deduced according to the test statistic. Subsequently, the filtering is proceeded by using the nonlocal weighted estimation. The performance of the proposed filter is tested with the simulated images and real PolSAR images, which are acquired by AIRSAR system and ESAR system. The qualitative and quantitative experiments indicate the validity of the proposed method by comparing with the widely-used despeckling methods.

  4. Polarimetric SAR image classification based on discriminative dictionary learning model

    Science.gov (United States)

    Sang, Cheng Wei; Sun, Hong

    2018-03-01

    Polarimetric SAR (PolSAR) image classification is one of the important applications of PolSAR remote sensing. It is a difficult high-dimension nonlinear mapping problem, the sparse representations based on learning overcomplete dictionary have shown great potential to solve such problem. The overcomplete dictionary plays an important role in PolSAR image classification, however for PolSAR image complex scenes, features shared by different classes will weaken the discrimination of learned dictionary, so as to degrade classification performance. In this paper, we propose a novel overcomplete dictionary learning model to enhance the discrimination of dictionary. The learned overcomplete dictionary by the proposed model is more discriminative and very suitable for PolSAR classification.

  5. Low-SAR metamaterial-inspired printed monopole antenna

    Science.gov (United States)

    Hossain, M. I.; Faruque, M. R. I.; Islam, M. T.; Ali, M. T.

    2017-01-01

    In this paper, a low-SAR metamaterial-embedded planar monopole antenna is introduced for a wireless communication system. A printed monopole antenna is designed for modern mobile, which operates in GSM, UMTS, LTE, WLAN, and Bluetooth frequency bands. A metamaterial structure is designed to use in the mobile handset with a multi-band printed monopole antenna. The finite integration technique of the CST microwave studio is used in this study. The measurement of antenna performances is taken in an anechoic chamber, and the SAR values are measured using COMOSAR system. The results indicate that metamaterial structure leads to reduce SAR without affecting antenna performance significantly. According to the measured results, the metamaterial attachment leads to reduce 87.7% peak SAR, 68.2% 1-g SAR, and 46.78% 10-g SAR compared to antenna without metamaterial.

  6. MRI screening on bone ischemia of hip and knee in recovered SARS patients

    International Nuclear Information System (INIS)

    Cheng Xiaoguang; Qu Hui; Liu Wei; Sun Jing; Cheng Kebin; Feng Suchen; Li Xiaosong

    2004-01-01

    Objective: To screen ischemia in the hip and knee joints of recovered SARS patients with MRI, and to investigate the prevalence rate of bone ischemia in those patients and its relationship with the use of steroid. Methods: Hip and knee MRI examinations were performed in 76 recovered SARS patients. There were 17 males and 59 females. Eight patients were treated without steroid, while 68 patients with steroid. Dose and duration of steroid usage were available in 30 out of 68 patients. The MRI images were read by senior radiologists to determine whether bone ischemia and/or osteonecrosis was present. Appropriate statistic analysis was performed to determine the significance of difference between groups. Results: (1) The MRI appearance of osteonecrosis in femoral head and condyle and bone infarct in bone marrow found in SARS patients was identical to those caused by other conditions (including steroid usage in other diseases). (2) No one of 8 SARS without steroid developed osteonecrosis, while 25 out of 68 steroid users had osteonecrosis found by MRI screening, and the difference in prevalence of osteonecrosis between these 2 groups was significant. In 25 patients with osteonecrosis, 20 of them involved more than one joints. Osteonecrosis involved 32 femoral heads, 26 femoral condyles, and 6 in femoral and tibial shafts. Thirteen patients with osteonecrosis had greater total steroid dose, greater daily dose, and longer duration than those (17 patients) without osteonecrosis, however, the differences between the two groups were not statistically significant. Sixty-four patients out of 76 complained pain in joints, 50 of them had multiple joint pains. The pain was reported in hips in 40 cases, followed by knees in 36, low backs in 10, shoulders in 7, and wrists in 4, respectively. The differences in frequency of pain between steroid users and non-steroid users, as well as between osteonecrosis and non-osteonecrosis were not significant. Conclusion: MRI is recommended for

  7. AN UNSUPERVISED CHANGE DETECTION BASED ON TEST STATISTIC AND KI FROM MULTI-TEMPORAL AND FULL POLARIMETRIC SAR IMAGES

    Directory of Open Access Journals (Sweden)

    J. Q. Zhao

    2016-06-01

    Full Text Available Accurate and timely change detection of Earth’s surface features is extremely important for understanding relationships and interactions between people and natural phenomena. Many traditional methods of change detection only use a part of polarization information and the supervised threshold selection. Those methods are insufficiency and time-costing. In this paper, we present a novel unsupervised change-detection method based on quad-polarimetric SAR data and automatic threshold selection to solve the problem of change detection. First, speckle noise is removed for the two registered SAR images. Second, the similarity measure is calculated by the test statistic, and automatic threshold selection of KI is introduced to obtain the change map. The efficiency of the proposed method is demonstrated by the quad-pol SAR images acquired by Radarsat-2 over Wuhan of China.

  8. Surface Deformation Observed by InSAR due to Fluid Injection: a Test Study in the Central U.S.

    Science.gov (United States)

    Deng, F.; Dixon, T. H.

    2017-12-01

    The central and eastern U.S. has undergone a dramatic increase in seismicity over the past few years. Many of these recent earthquakes were likely induced by human activities, with underground fluid injection for oil and gas extraction being one of the main contributors. Surface deformation caused by fluid injection has been captured by GPS and InSAR observations in several areas. For example, surface uplift of up to 10 cm due to CO2 injection between 2007 and 2011 was measured by InSAR at an enhanced oil recovery site in west Texas. We are using Texas and Oklahoma as test areas to analyze the potential relationship between surface deformation, underground fluid injection and induced earthquakes. C-band SAR data from ENVISAT and Sentinel-1, and L-band SAR data from ALOS and ALOS-2 are used to form decade-long time series. Based on the surface deformation derived from the time series InSAR data, subsurface volume change and volumetric strain in an elastic half space are estimated. Seismic data provided by the USGS are used to analyze the spatial and temporal distribution pattern of earthquakes, and the potential link between surface deformation and induced earthquakes. The trigger mechanism will be combined with forward modeling to predict seismicity and assess related hazard for future study.

  9. Tropical forest plantation biomass estimation using RADARSAT-SAR and TM data of south china

    Science.gov (United States)

    Wang, Chenli; Niu, Zheng; Gu, Xiaoping; Guo, Zhixing; Cong, Pifu

    2005-10-01

    Forest biomass is one of the most important parameters for global carbon stock model yet can only be estimated with great uncertainties. Remote sensing, especially SAR data can offers the possibility of providing relatively accurate forest biomass estimations at a lower cost than inventory in study tropical forest. The goal of this research was to compare the sensitivity of forest biomass to Landsat TM and RADARSAT-SAR data and to assess the efficiency of NDVI, EVI and other vegetation indices in study forest biomass based on the field survey date and GIS in south china. Based on vegetation indices and factor analysis, multiple regression and neural networks were developed for biomass estimation for each species of the plantation. For each species, the better relationships between the biomass predicted and that measured from field survey was obtained with a neural network developed for the species. The relationship between predicted and measured biomass derived from vegetation indices differed between species. This study concludes that single band and many vegetation indices are weakly correlated with selected forest biomass. RADARSAT-SAR Backscatter coefficient has a relatively good logarithmic correlation with forest biomass, but neither TM spectral bands nor vegetation indices alone are sufficient to establish an efficient model for biomass estimation due to the saturation of bands and vegetation indices, multiple regression models that consist of spectral and environment variables improve biomass estimation performance. Comparing with TM, a relatively well estimation result can be achieved by RADARSAT-SAR, but all had limitations in tropical forest biomass estimation. The estimation results obtained are not accurate enough for forest management purposes at the forest stand level. However, the approximate volume estimates derived by the method can be useful in areas where no other forest information is available. Therefore, this paper provides a better

  10. Monitoring Building Deformation with InSAR: Experiments and Validation

    Science.gov (United States)

    Yang, Kui; Yan, Li; Huang, Guoman; Chen, Chu; Wu, Zhengpeng

    2016-01-01

    Synthetic Aperture Radar Interferometry (InSAR) techniques are increasingly applied for monitoring land subsidence. The advantages of InSAR include high accuracy and the ability to cover large areas; nevertheless, research validating the use of InSAR on building deformation is limited. In this paper, we test the monitoring capability of the InSAR in experiments using two landmark buildings; the Bohai Building and the China Theater, located in Tianjin, China. They were selected as real examples to compare InSAR and leveling approaches for building deformation. Ten TerraSAR-X images spanning half a year were used in Permanent Scatterer InSAR processing. These extracted InSAR results were processed considering the diversity in both direction and spatial distribution, and were compared with true leveling values in both Ordinary Least Squares (OLS) regression and measurement of error analyses. The detailed experimental results for the Bohai Building and the China Theater showed a high correlation between InSAR results and the leveling values. At the same time, the two Root Mean Square Error (RMSE) indexes had values of approximately 1 mm. These analyses show that a millimeter level of accuracy can be achieved by means of InSAR technique when measuring building deformation. We discuss the differences in accuracy between OLS regression and measurement of error analyses, and compare the accuracy index of leveling in order to propose InSAR accuracy levels appropriate for monitoring buildings deformation. After assessing the advantages and limitations of InSAR techniques in monitoring buildings, further applications are evaluated. PMID:27999403

  11. Monitoring Building Deformation with InSAR: Experiments and Validation

    Directory of Open Access Journals (Sweden)

    Kui Yang

    2016-12-01

    Full Text Available Synthetic Aperture Radar Interferometry (InSAR techniques are increasingly applied for monitoring land subsidence. The advantages of InSAR include high accuracy and the ability to cover large areas; nevertheless, research validating the use of InSAR on building deformation is limited. In this paper, we test the monitoring capability of the InSAR in experiments using two landmark buildings; the Bohai Building and the China Theater, located in Tianjin, China. They were selected as real examples to compare InSAR and leveling approaches for building deformation. Ten TerraSAR-X images spanning half a year were used in Permanent Scatterer InSAR processing. These extracted InSAR results were processed considering the diversity in both direction and spatial distribution, and were compared with true leveling values in both Ordinary Least Squares (OLS regression and measurement of error analyses. The detailed experimental results for the Bohai Building and the China Theater showed a high correlation between InSAR results and the leveling values. At the same time, the two Root Mean Square Error (RMSE indexes had values of approximately 1 mm. These analyses show that a millimeter level of accuracy can be achieved by means of InSAR technique when measuring building deformation. We discuss the differences in accuracy between OLS regression and measurement of error analyses, and compare the accuracy index of leveling in order to propose InSAR accuracy levels appropriate for monitoring buildings deformation. After assessing the advantages and limitations of InSAR techniques in monitoring buildings, further applications are evaluated.

  12. SAR11 bacteria linked to ocean anoxia and nitrogen loss

    DEFF Research Database (Denmark)

    Tsementzi, Despina; Wu, Jieying; Deutsch, Samuel

    2016-01-01

    Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas...... activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth’s most abundant organismal group....

  13. Prototype Theory Based Feature Representation for PolSAR Images

    OpenAIRE

    Huang Xiaojing; Yang Xiangli; Huang Pingping; Yang Wen

    2016-01-01

    This study presents a new feature representation approach for Polarimetric Synthetic Aperture Radar (PolSAR) image based on prototype theory. First, multiple prototype sets are generated using prototype theory. Then, regularized logistic regression is used to predict similarities between a test sample and each prototype set. Finally, the PolSAR image feature representation is obtained by ensemble projection. Experimental results of an unsupervised classification of PolSAR images show that our...

  14. Potential of X-Band TerraSAR-X and COSMO-SkyMed SAR Data for the Assessment of Physical Soil Parameters

    Directory of Open Access Journals (Sweden)

    Azza Gorrab

    2015-01-01

    Full Text Available The aim of this paper is to analyze the potential of X-band SAR measurements (COSMO-SkyMed and TerraSAR-X made over bare soils for the estimation of soil moisture and surface geometry parameters at a semi-arid site in Tunisia (North Africa. Radar signals acquired with different configurations (HH and VV polarizations, incidence angles of 26° and 36° are statistically compared with ground measurements (soil moisture and roughness parameters. The radar measurements are found to be highly sensitive to the various soil parameters of interest. A linear relationship is determined for the radar signals as a function of volumetric soil moisture, and a logarithmic correlation is observed between the radar signals and three surface roughness parameters: the root mean square height (Hrms, the parameter Zs = Hrms2/l (where l is the correlation length and the parameter Zg = Hrms × (Hrms/lα (where α is the power of the surface height correlation function. The highest dynamic sensitivity is observed for Zg at high incidence angles. Finally, the performance of different physical and semi-empirical backscattering models (IEM, Baghdadi-calibrated IEM and Dubois models is compared with SAR measurements. The results provide an indication of the limits of validity of the IEM and Dubois models, for various radar configurations and roughness conditions. Considerable improvements in the IEM model performance are observed using the Baghdadi-calibrated version of this model.

  15. Synthesis, SAR and biological evaluation of a novel series of 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl) urea: Organoselenium compounds for cancer therapy.

    Science.gov (United States)

    Ye, S; Zheng, X; Hu, T; Zeng, H

    2016-06-30

    Thioredoxin reductase 1 (TrxR1) is an important potential anticancer drug target and closely related to both carcinogenesis and cancer progression. Ethaselen (BBSKE), a novel organoselenium compound inhibiting TrxR1 with selective antitumor effect, while its symmetrical structure results in poor solubility. Carmustine (BCNU), a DNA cross-link agent and also a deactivator of TrxR, is with high toxicity and low selectivity which limit its clinical application to some extents. Herein, a novel compound, 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea(4a-1), which was designed through the combination of Ethaselen and Carmustine, showed good solubility, good tagetability, low toxicity and excellent antitumor activity by synergism. Using the structure of 4a-1 as a key active scaffold, a series of novel 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea was designed, synthesized and evaluated to explore the structure-activity relationships (SARs) of these inhibitors and to improve their antitumor activities. Notably, 1-(2-chloroethyl)-3-(2-(6-fluoro-3-oxobenzoselenazol-2(3H)-yl)ethyl)-1-nitrosourea(4b-1) was found to exhibit more potent antitumor activities comparable to 4a-1 against all the four cancer cell lines, including Mia PaCa-2, PANC-1, RKO, LoVo. These results have highlighted compound 4b-1 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents. In addition, a SAR model was established to conduct further structural modification.

  16. Evaluation of the Wishart test statistics for polarimetric SAR data

    DEFF Research Database (Denmark)

    Skriver, Henning; Nielsen, Allan Aasbjerg; Conradsen, Knut

    2003-01-01

    A test statistic for equality of two covariance matrices following the complex Wishart distribution has previously been used in new algorithms for change detection, edge detection and segmentation in polarimetric SAR images. Previously, the results for change detection and edge detection have been...... quantitatively evaluated. This paper deals with the evaluation of segmentation. A segmentation performance measure originally developed for single-channel SAR images has been extended to polarimetric SAR images, and used to evaluate segmentation for a merge-using-moment algorithm for polarimetric SAR data....

  17. SAR Subsets for Selected Field Sites, 2007-2010

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: This data set provides Synthetic Aperture Radar (SAR) images for 42 selected sites from various terrestrial ecology and meteorological monitoring networks...

  18. SAR Subsets for Selected Field Sites, 2007-2010

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set provides Synthetic Aperture Radar (SAR) images for 42 selected sites from various terrestrial ecology and meteorological monitoring networks including...

  19. Applications of SAR Interferometry in Earth and Environmental Science Research

    Science.gov (United States)

    Zhou, Xiaobing; Chang, Ni-Bin; Li, Shusun

    2009-01-01

    This paper provides a review of the progress in regard to the InSAR remote sensing technique and its applications in earth and environmental sciences, especially in the past decade. Basic principles, factors, limits, InSAR sensors, available software packages for the generation of InSAR interferograms were summarized to support future applications. Emphasis was placed on the applications of InSAR in seismology, volcanology, land subsidence/uplift, landslide, glaciology, hydrology, and forestry sciences. It ends with a discussion of future research directions. PMID:22573992

  20. Applications of SAR Interferometry in Earth and Environmental Science Research

    Directory of Open Access Journals (Sweden)

    Xiaobing Zhou

    2009-03-01

    Full Text Available This paper provides a review of the progress in regard to the InSAR remote sensing technique and its applications in earth and environmental sciences, especially in the past decade. Basic principles, factors, limits, InSAR sensors, available software packages for the generation of InSAR interferograms were summarized to support future applications. Emphasis was placed on the applications of InSAR in seismology, volcanology, land subsidence/uplift, landslide, glaciology, hydrology, and forestry sciences. It ends with a discussion of future research directions.

  1. Applications of SAR Interferometry in Earth and Environmental Science Research.

    Science.gov (United States)

    Zhou, Xiaobing; Chang, Ni-Bin; Li, Shusun

    2009-01-01

    This paper provides a review of the progress in regard to the InSAR remote sensing technique and its applications in earth and environmental sciences, especially in the past decade. Basic principles, factors, limits, InSAR sensors, available software packages for the generation of InSAR interferograms were summarized to support future applications. Emphasis was placed on the applications of InSAR in seismology, volcanology, land subsidence/uplift, landslide, glaciology, hydrology, and forestry sciences. It ends with a discussion of future research directions.

  2. Genome organization of the SARS-CoV

    DEFF Research Database (Denmark)

    Xu, Jing; Hu, Jianfei; Wang, Jing

    2003-01-01

    Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available or devel......Annotation of the genome sequence of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) is indispensable to understand its evolution and pathogenesis. We have performed a full annotation of the SARS-CoV genome sequences by using annotation programs publicly available...

  3. The use of comprehensive two-dimensional gas chromatography and structure-activity modeling for screening and preliminary risk assessment of organic contaminants in soil, sediment, and surface water

    Energy Technology Data Exchange (ETDEWEB)

    Moreira Bastos, Patricia; Haglund, Peter [Umeaa Univ. (Sweden). Dept. of Chemistry

    2012-08-15

    Purpose: This article aims to investigate the use and benefits of using comprehensive two-dimensional gas chromatography (GC x GC) and structure-activity relationship modeling for screening and prioritization of organic contaminants in complex matrices. The benefit of applying comprehensive screening techniques to samples with high organic contaminant content is primarily that compounds with diverse physicochemical properties can be analyzed simultaneously. Here, a heavily contaminated industrial area was surveyed for organic pollutants by analyzing soil, sediment, and surface water samples. The hazard of the pollutants were ranked using SARs. Material and methods: The water samples were liquid-liquid extracted using dichloromethane and directly analyzed by GC x GC-time-of-flight mass spectrometry (GC x GC-TofMS). Soil and sediment samples were extracted with dichloromethane in an ultrasonic bath and subjected to gel permeation chromatography to eliminate lipids and humic matter. The low molecular weight fraction was then analyzed with GC x GC-TofMS. Results and discussion: More than 10,000 components were found in each sample, of which ca. 300 individual compounds were unambiguously identified using the National Institute of Standards and Technology mass spectra library and authentic reference standards. Alkanes, polycyclic aromatic hydrocarbons, and phthalates were generally the most abundant and were found in all matrices. In contrast, chlorinated compounds such as chlorophenols, biphenyls, and chlorinated pesticides were only detected in samples from a few hotspot regions. The toxicities of the most frequently detected compounds and of the compounds detected at the highest concentrations in samples from hotspot regions were estimated by ecological structure-activity relationships. The ratio of the measured concentration to the predicted toxicity level was then calculated for each compound and used for an initial risk assessment in order to prioritize compounds

  4. InSAR atmospheric correction using Himawari-8 Geostationary Meteorological Satellite

    Science.gov (United States)

    Kinoshita, Y.; Nimura, T.; Furuta, R.

    2017-12-01

    The atmospheric delay effect is one of the limitations for the accurate surface displacement detection by Synthetic Aperture Radar Interferometry (InSAR). Many previous studies have attempted to mitigate the neutral atmospheric delay in InSAR (e.g. Jolivet et al. 2014; Foster et al. 2006; Kinoshita et al. 2013). Hanssen et al. (2001) investigated the relationship between the 27 hourly observations of GNSS precipitable water vapor (PWV) and the infrared brightness temperature derived from visible satellite imagery, and showed a good correlation. Here we showed a preliminary result of the newly developed method for the neutral atmospheric delay correction using the Himawari-8 Japanese geostationary meteorological satellite data. The Himawari-8 satellite is the Japanese state-of-the-art geostationary meteorological satellite that has 16 observation channels and has spatial resolutions of 0.5 km (visible) and 2.0 km (near-infrared and infrared) with an time interval of 2.5 minutes around Japan. To estimate the relationship between the satellite brightness temperature and the atmospheric delay amount. Since the InSAR atmospheric delay is principally the same as that in GNSS, we at first compared the Himawari-8 data with the GNSS zenith tropospheric delay data derived from the Japanese dense GNSS network. The comparison of them showed that the band with the wavelength of 6.9 μm had the highest correlation to the GNSS observation. Based on this result, we developed an InSAR atmospheric delay model that uses the Himawari-8 6.9 μm band data. For the model validation, we generated InSAR images from the ESA's C-band Sentinel-1 SLC data with the GAMMA SAR software. We selected two regions around Tokyo and Sapporo (both in Japan) as the test sites because of the less temporal decorrelation. The validation result showed that the delay model reasonably estimate large scale phase variation whose spatial scale was on the order of over 20 km. On the other hand, phase variations of

  5. Feature Matching for SAR and Optical Images Based on Gaussian-Gamma-shaped Edge Strength Map

    Directory of Open Access Journals (Sweden)

    CHEN Min

    2016-03-01

    Full Text Available A matching method for SAR and optical images, robust to pixel noise and nonlinear grayscale differences, is presented. Firstly, a rough correction to eliminate rotation and scale change between images is performed. Secondly, features robust to speckle noise of SAR image are detected by improving the original phase congruency based method. Then, feature descriptors are constructed on the Gaussian-Gamma-shaped edge strength map according to the histogram of oriented gradient pattern. Finally, descriptor similarity and geometrical relationship are combined to constrain the matching processing.The experimental results demonstrate that the proposed method provides significant improvement in correct matches number and image registration accuracy compared with other traditional methods.

  6. Satellite on-board real-time SAR processor prototype

    Science.gov (United States)

    Bergeron, Alain; Doucet, Michel; Harnisch, Bernd; Suess, Martin; Marchese, Linda; Bourqui, Pascal; Desnoyers, Nicholas; Legros, Mathieu; Guillot, Ludovic; Mercier, Luc; Châteauneuf, François

    2017-11-01

    A Compact Real-Time Optronic SAR Processor has been successfully developed and tested up to a Technology Readiness Level of 4 (TRL4), the breadboard validation in a laboratory environment. SAR, or Synthetic Aperture Radar, is an active system allowing day and night imaging independent of the cloud coverage of the planet. The SAR raw data is a set of complex data for range and azimuth, which cannot be compressed. Specifically, for planetary missions and unmanned aerial vehicle (UAV) systems with limited communication data rates this is a clear disadvantage. SAR images are typically processed electronically applying dedicated Fourier transformations. This, however, can also be performed optically in real-time. Originally the first SAR images were optically processed. The optical Fourier processor architecture provides inherent parallel computing capabilities allowing real-time SAR data processing and thus the ability for compression and strongly reduced communication bandwidth requirements for the satellite. SAR signal return data are in general complex data. Both amplitude and phase must be combined optically in the SAR processor for each range and azimuth pixel. Amplitude and phase are generated by dedicated spatial light modulators and superimposed by an optical relay set-up. The spatial light modulators display the full complex raw data information over a two-dimensional format, one for the azimuth and one for the range. Since the entire signal history is displayed at once, the processor operates in parallel yielding real-time performances, i.e. without resulting bottleneck. Processing of both azimuth and range information is performed in a single pass. This paper focuses on the onboard capabilities of the compact optical SAR processor prototype that allows in-orbit processing of SAR images. Examples of processed ENVISAT ASAR images are presented. Various SAR processor parameters such as processing capabilities, image quality (point target analysis), weight and

  7. MULTI-TEMPORAL SAR INTERFEROMETRY FOR LANDSLIDE MONITORING

    Directory of Open Access Journals (Sweden)

    R. Dwivedi

    2016-06-01

    Full Text Available In the past few years, SAR Interferometry specially InSAR and D-InSAR were extensively used for deformation monitoring related applications. Due to temporal and spatial decorrelation in dense vegetated areas, effectiveness of InSAR and D-InSAR observations were always under scrutiny. Multi-temporal InSAR methods are developed in recent times to retrieve the deformation signal from pixels with different scattering characteristics. Presently, two classes of multi-temporal InSAR algorithms are available- Persistent Scatterer (PS and Small Baseline (SB methods. This paper discusses the Stanford Method for Persistent Scatterer (StaMPS based PS-InSAR and the Small Baselines Subset (SBAS techniques to estimate the surface deformation in Tehri dam reservoir region in Uttarkhand, India. Both PS-InSAR and SBAS approaches used sixteen ENVISAT ASAR C-Band images for generating single master and multiple master interferograms stack respectively and their StaMPS processing resulted in time series 1D-Line of Sight (LOS mean velocity maps which are indicative of deformation in terms of movement towards and away from the satellites. From 1D LOS velocity maps, localization of landslide is evident along the reservoir rim area which was also investigated in the previous studies. Both PS-InSAR and SBAS effectively extract measurement pixels in the study region, and the general results provided by both approaches show a similar deformation pattern along the Tehri reservoir region. Further, we conclude that StaMPS based PS-InSAR method performs better in terms of extracting more number of measurement pixels and in the estimation of mean Line of Sight (LOS velocity as compared to SBAS method. It is also proposed to take up a few major landslides area in Uttarakhand for slope stability assessment.

  8. Impact of the Regulators SigB, Rot, SarA and sarS on the Toxic Shock Tst Promoter and TSST-1 Expression in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Diego O Andrey

    Full Text Available Staphylococcus aureus is an important pathogen manifesting virulence through diverse disease forms, ranging from acute skin infections to life-threatening bacteremia or systemic toxic shock syndromes. In the latter case, the prototypical superantigen is TSST-1 (Toxic Shock Syndrome Toxin 1, encoded by tst(H, and carried on a mobile genetic element that is not present in all S. aureus strains. Transcriptional regulation of tst is only partially understood. In this study, we dissected the role of sarA, sarS (sarH1, RNAIII, rot, and the alternative stress sigma factor sigB (σB. By examining tst promoter regulation predominantly in the context of its native sequence within the SaPI1 pathogenicity island of strain RN4282, we discovered that σB emerged as a particularly important tst regulator. We did not detect a consensus σB site within the tst promoter, and thus the effect of σB is likely indirect. We found that σB strongly repressed the expression of the toxin via at least two distinct regulatory pathways dependent upon sarA and agr. Furthermore rot, a member of SarA family, was shown to repress tst expression when overexpressed, although its deletion had no consistent measurable effect. We could not find any detectable effect of sarS, either by deletion or overexpression, suggesting that this regulator plays a minimal role in TSST-1 expression except when combined with disruption of sarA. Collectively, our results extend our understanding of complex multifactorial regulation of tst, revealing several layers of negative regulation. In addition to environmental stimuli thought to impact TSST-1 production, these findings support a model whereby sporadic mutation in a few key negative regulators can profoundly affect and enhance TSST-1 expression.

  9. Beyond PSInSAR: the SQUEESAR Approach

    Science.gov (United States)

    Ferretti, A.; Novali, F.; Fumagalli, A.; Prati, C.; Rocca, F.; Rucci, A.

    2009-12-01

    After a decade since the first results on ERS data, Permanent Scatterer (PS) InSAR has become an operational technology for detecting and monitoring slow surface deformation phenomena such as subsidence and uplift, landslides, seismic fault creeping, volcanic inflation, etc. Processing procedures have been continuously updated, but the core of the algorithm has not been changed significantly. As well known, in PSInSAR, the main target is the identification of individual pixels that exhibit a “PS behavior”, i.e. they are only slightly affected by both temporal and geometrical decorrelation. Typically, these scatterers correspond to man-made objects, but PS have been identified also in non-urban areas, where exposed rocks or outcrops can indeed create good radar benchmarks and enable high-quality displacement measurements. Contrary to interferogram stacking techniques, PS analyses are carried out on a pixel-by-pixel basis, with no filtering of the interferograms, in order to preserve phase values from possible incoherent clutter surrounding good radar targets. In fact, any filtering process implies a spatial smoothing of the data that could compromise - rather than improve - phase coherence, at least for isolated PS. Although the PS approach usually allows one to retrieve high quality deformation measurements on a sparse grid of good radar targets, in some datasets it is quite evident how the number of pixels where some information can be extracted could be significantly increased by relaxing the hypothesis on target coherence and searching for pixels where the coherence level is high enough at least in some interferograms of the data-stack, not necessarily all. The idea of computing a “coherence matrix” for each pixel of the area of interest have been already proposed in previous papers, together with a statistical estimation of some physical parameters of interest (e.g. the average displacement rate) based on the covariance matrix. In past publications

  10. Permanent scatterer InSAR processing: Forsmark

    International Nuclear Information System (INIS)

    Dehls, John F.

    2006-04-01

    It has been speculated that slow, aseismic movement may be occurring along some of the fracture zones crosscutting the Forsmark area. The purpose of this study is to determine if it is possible to measure such movement using dInSAR. Differential SAR Interferometry (DInSAR) is a technique that compares the phases of multiple radar images of an area to measure surface change. The method has the potential to detect millimetric surface deformation along the sensor - target line-of-sight. Differences in phase between two images are easily viewed by combining, or interfering, the two phase-images. In the resulting image, the waves will either reinforce or cancel one another, depending upon the relative phases. The resulting image is called an interferogram and contains concentric bands of colour, or fringes, that are related to topography and/or surface deformation. New algorithms use many images acquired over a long time period to determine the movement history of individual objects, referred to as permanent scatterers. In the current project, standard PSInSAR processing was performed on 40 ERS-1 and ERS-2 scenes. The total area processed is approximately 1,500 km 2 . Slightly less than 20,000 permanent scatterers were identified.The highest densities were obtained along the coast and on the islands, where natural outcrops are more abundant. Two main classes of objects act as permanent scatterers in this area. The first are natural reflectors, such as rocks. The second are man-made reflectors, such as parts of buildings. Numerous local movements were found in the study area, relating to building subsidence, or compaction of anthropogenic fill. The dataset was divided into three groups for analysis, based upon the location of regional lineaments provided by SKB. Both statistical and geostatistical techniques were used. The median velocity of the three blocks did not differ by more than 0.2 mm/yr. This is not considered significant, given the possible magnitude of errors

  11. Bioinformatics analysis of SARS coronavirus genome polymorphism

    Directory of Open Access Journals (Sweden)

    Pavlović-Lažetić Gordana M

    2004-05-01

    Full Text Available Abstract Background We have compared 38 isolates of the SARS-CoV complete genome. The main goal was twofold: first, to analyze and compare nucleotide sequences and to identify positions of single nucleotide polymorphism (SNP, insertions and deletions, and second, to group them according to sequence similarity, eventually pointing to phylogeny of SARS-CoV isolates. The comparison is based on genome polymorphism such as insertions or deletions and the number and positions of SNPs. Results The nucleotide structure of all 38 isolates is presented. Based on insertions and deletions and dissimilarity due to SNPs, the dataset of all the isolates has been qualitatively classified into three groups each having their own subgroups. These are the A-group with "regular" isolates (no insertions / deletions except for 5' and 3' ends, the B-group of isolates with "long insertions", and the C-group of isolates with "many individual" insertions and deletions. The isolate with the smallest average number of SNPs, compared to other isolates, has been identified (TWH. The density distribution of SNPs, insertions and deletions for each group or subgroup, as well as cumulatively for all the isolates is also presented, along with the gene map for TWH. Since individual SNPs may have occurred at random, positions corresponding to multiple SNPs (occurring in two or more isolates are identified and presented. This result revises some previous results of a similar type. Amino acid changes caused by multiple SNPs are also identified (for the annotated sequences, as well as presupposed amino acid changes for non-annotated ones. Exact SNP positions for the isolates in each group or subgroup are presented. Finally, a phylogenetic tree for the SARS-CoV isolates has been produced using the CLUSTALW program, showing high compatibility with former qualitative classification. Conclusions The comparative study of SARS-CoV isolates provides essential information for genome

  12. Two dimensional estimates from ocean SAR images

    Directory of Open Access Journals (Sweden)

    J. M. Le Caillec

    1996-01-01

    Full Text Available Synthetic Aperture Radar (SAR images of the ocean yield a lot of information on the sea-state surface providing that the mapping process between the surface and the image is clearly defined. However it is well known that SAR images exhibit non-gaussian statistics and that the motion of the scatterers on the surface, while the image is being formed, may yield to nonlinearities. The detection and quantification of these nonlinearities are made possible by using Higher Order Spectra (HOS methods and more specifically, bispectrum estimation. The development of the latter method allowed us to find phase relations between different parts of the image and to recognise their level of coupling, i.e. if and how waves of different wavelengths interacted nonlinearly. This information is quite important as the usual models assume strong nonlinearities when the waves are propagating in the azimuthal direction (i.e. along the satellite track and almost no nonlinearities when propagating in the range direction. In this paper, the mapping of the ocean surface to the SAR image is reinterpreted and a specific model (i.e. a Second Order Volterra Model is introduced. The nonlinearities are thus explained as either produced by a nonlinear system or due to waves propagating into selected directions (azimuth or range and interacting during image formation. It is shown that quadratic nonlinearities occur for waves propagating near the range direction while for those travelling in the azimuthal direction the nonlinearities, when present, are mostly due to wave interactions but are almost completely removed by the filtering effect coming from the surface motion itself (azimuth cut-off. An inherent quadratic interaction filtering (azimuth high pass filter is also present. But some other effects, apparently nonlinear, are not detected with the methods described here, meaning that either the usual relation developed for the Ocean-to-SAR transform is somewhat incomplete

  13. Cross-calibration of interferometric SAR data

    DEFF Research Database (Denmark)

    Dall, Jørgen

    2003-01-01

    Generation of digital elevation models from interferometric synthetic aperture radar (SAR) data is a well established technique. Achieving a high geometric fidelity calls for a calibration accounting for inaccurate navigation data and system parameters as well as system imperfections. Fully...... automated calibration techniques are preferable, especially for operational mapping. The author presents one such technique, called cross-calibration. Though developed for single-pass interferometry, it may be applicable to multi-pass interferometry, too. Cross-calibration requires stability during mapping...... ground control point is often needed. The paper presents the principles and mathematics of the cross-calibration technique and illustrates its successful application to EMISAR data....

  14. Detection of land degradation with polarimetric SAR

    Science.gov (United States)

    Ray, Terrill W.; Farr, Tom G.; Van Zyl, Jakob J.

    1992-01-01

    Multispectral radar polarimeter data were collected over the Manix Basin Area of the Mojave desert using an airborne SAR. An analysis of the data reveals unusual polarization responses which are attributed to the formation of wind ripples on the surfaces of fields that have been abandoned for more than 5 years. This hypothesis has been confirmed through field observations, and a second-order perturbation model is shown to effectively model the polarization responses. The results demonstrate the usefulness of remote sensing techniques for the study of land degradation at synoptic scales.

  15. Permanent scatterer InSAR processing: Forsmark

    Energy Technology Data Exchange (ETDEWEB)

    Dehls, John F [Geological Survey of Norway, Trondheim (Norway)

    2006-04-15

    It has been speculated that slow, aseismic movement may be occurring along some of the fracture zones crosscutting the Forsmark area. The purpose of this study is to determine if it is possible to measure such movement using dInSAR. Differential SAR Interferometry (DInSAR) is a technique that compares the phases of multiple radar images of an area to measure surface change. The method has the potential to detect millimetric surface deformation along the sensor - target line-of-sight. Differences in phase between two images are easily viewed by combining, or interfering, the two phase-images. In the resulting image, the waves will either reinforce or cancel one another, depending upon the relative phases. The resulting image is called an interferogram and contains concentric bands of colour, or fringes, that are related to topography and/or surface deformation. New algorithms use many images acquired over a long time period to determine the movement history of individual objects, referred to as permanent scatterers. In the current project, standard PSInSAR processing was performed on 40 ERS-1 and ERS-2 scenes. The total area processed is approximately 1,500 km{sup 2}. Slightly less than 20,000 permanent scatterers were identified.The highest densities were obtained along the coast and on the islands, where natural outcrops are more abundant. Two main classes of objects act as permanent scatterers in this area. The first are natural reflectors, such as rocks. The second are man-made reflectors, such as parts of buildings. Numerous local movements were found in the study area, relating to building subsidence, or compaction of anthropogenic fill. The dataset was divided into three groups for analysis, based upon the location of regional lineaments provided by SKB. Both statistical and geostatistical techniques were used. The median velocity of the three blocks did not differ by more than 0.2 mm/yr. This is not considered significant, given the possible magnitude of

  16. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy

    Directory of Open Access Journals (Sweden)

    Kliger Yossef

    2003-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is a febrile respiratory illness. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus (SARS-CoV, whose genome was recently sequenced. Since it is a member of the Coronaviridae, its spike protein (S2 is believed to play a central role in viral entry by facilitating fusion between the viral and host cell membranes. The protein responsible for viral-induced membrane fusion of HIV-1 (gp41 differs in length, and has no sequence homology with S2. Results Sequence analysis reveals that the two viral proteins share the sequence motifs that construct their active conformation. These include (1 an N-terminal leucine/isoleucine zipper-like sequence, and (2 a C-terminal heptad repeat located upstream of (3 an aromatic residue-rich region juxtaposed to the (4 transmembrane segment. Conclusions This study points to a similar mode of action for the two viral proteins, suggesting that anti-viral strategy that targets the viral-induced membrane fusion step can be adopted from HIV-1 to SARS-CoV. Recently the FDA approved Enfuvirtide, a synthetic peptide corresponding to the C-terminal heptad repeat of HIV-1 gp41, as an anti-AIDS agent. Enfuvirtide and C34, another anti HIV-1 peptide, exert their inhibitory activity by binding to a leucine/isoleucine zipper-like sequence in gp41, thus inhibiting a conformational change of gp41 required for its activation. We suggest that peptides corresponding to the C-terminal heptad repeat of the S2 protein may serve as inhibitors for SARS-CoV entry.

  17. Mapping mountain meadow with high resolution and polarimetric SAR data

    International Nuclear Information System (INIS)

    Tian, Bangsen; Li, Zhen; Xu, Juan; Fu, Sitao; Liu, Jiuli

    2014-01-01

    This paper presents a method to map the large grassland in the eastern margin of the Tibetan Plateau with the high resolution polarimetric SAR (PolSAR) imagery. When PolSAR imagery is used for land cover classification, the brightness of a SAR image is affected by topography due to varying projection between ground and image coordinates. The objective of this paper is twofold: (1) we first extend the theory of SAR terrain correction to the polarimetric case, to utilize the entire available polarimetric signature, where correction is performed explicitly based on a matrix format like covariance matrix. (2) Next, the orthoectified PolSAR is applied to classify mountain meadow and investigate the potential of PolSAR in mapping grassland. In this paper, the gamma naught radiometric correction estimates the local illuminated area at each grid point in the radar geometry. Then, each element of the coherency matrix is divided by the local area to produce a polarimetric product. Secondly, the impact of radiometric correction upon classification accuracy is investigated. A supervised classification is performed on the orthorectified Radarsat-2 PolSAR to map the spatial distribution of meadow and evaluate monitoring capabilities of mountain meadow

  18. Molecular mechanisms of severe acute respiratory syndrome (SARS

    Directory of Open Access Journals (Sweden)

    Zabel Peter

    2005-01-01

    Full Text Available Abstract Severe acute respiratory syndrome (SARS is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.

  19. Synthetic aperture design for increased SAR image rate

    Science.gov (United States)

    Bielek, Timothy P [Albuquerque, NM; Thompson, Douglas G [Albuqerque, NM; Walker, Bruce C [Albuquerque, NM

    2009-03-03

    High resolution SAR images of a target scene at near video rates can be produced by using overlapped, but nevertheless, full-size synthetic apertures. The SAR images, which respectively correspond to the apertures, can be analyzed in sequence to permit detection of movement in the target scene.

  20. Calibration of SAR probes in waveguide at 900 MHz

    International Nuclear Information System (INIS)

    Jokela, K.; Puranen, L.; Hyysalo, P.

    1998-01-01

    The radiation safety tests for hand-held mobile phones require precise calibration of the small electric field probes used for the measurement of SAR in phantoms simulating the human body. In this study a calibration based on a rectangular waveguide was developed for SAR calibrations at 900 MHz

  1. Training Convolutional Neural Networks for Translational Invariance on SAR ATR

    DEFF Research Database (Denmark)

    Malmgren-Hansen, David; Engholm, Rasmus; Østergaard Pedersen, Morten

    2016-01-01

    In this paper we present a comparison of the robustness of Convolutional Neural Networks (CNN) to other classifiers in the presence of uncertainty of the objects localization in SAR image. We present a framework for simulating simple SAR images, translating the object of interest systematically...

  2. Multi-look polarimetric SAR image filtering using simulated annealing

    DEFF Research Database (Denmark)

    Schou, Jesper

    2000-01-01

    Based on a previously published algorithm capable of estimating the radar cross-section in synthetic aperture radar (SAR) intensity images, a new filter is presented utilizing multi-look polarimetric SAR images. The underlying mean covariance matrix is estimated from the observed sample covariance...

  3. The Danish polarimetric SAR for remote sensing applications

    DEFF Research Database (Denmark)

    Christensen, Erik Lintz; Madsen, Søren Nørvang; Dall, Jørgen

    1994-01-01

    Presents the Danish polarimetric SAR system, EMISAR, and the approach taken in the system design to achieve a reliable high performance system. The design and implementation of the antenna system as well as the analog and digital hardware are discussed. The SAR utilises a dual polarised microstri...

  4. Demonstrator for Automatic Target Classification in SAR Imagery

    NARCIS (Netherlands)

    Wit, J.J.M. de; Broek, A.C. van den; Dekker, R.J.

    2006-01-01

    Due to the increasing use of unmanned aerial vehicles (UAV) for reconnaissance, surveillance, and target acquisition applications, the interest in synthetic aperture radar (SAR) systems is growing. In order to facilitate the processing of the enormous amount of SAR data on the ground, automatic

  5. An Adaptive Ship Detection Scheme for Spaceborne SAR Imagery

    Directory of Open Access Journals (Sweden)

    Xiangguang Leng

    2016-08-01

    Full Text Available With the rapid development of spaceborne synthetic aperture radar (SAR and the increasing need of ship detection, research on adaptive ship detection in spaceborne SAR imagery is of great importance. Focusing on practical problems of ship detection, this paper presents a highly adaptive ship detection scheme for spaceborne SAR imagery. It is able to process a wide range of sensors, imaging modes and resolutions. Two main stages are identified in this paper, namely: ship candidate detection and ship discrimination. Firstly, this paper proposes an adaptive land masking method using ship size and pixel size. Secondly, taking into account the imaging mode, incidence angle, and polarization channel of SAR imagery, it implements adaptive ship candidate detection in spaceborne SAR imagery by applying different strategies to different resolution SAR images. Finally, aiming at different types of typical false alarms, this paper proposes a comprehensive ship discrimination method in spaceborne SAR imagery based on confidence level and complexity analysis. Experimental results based on RADARSAT-1, RADARSAT-2, TerraSAR-X, RS-1, and RS-3 images demonstrate that the adaptive scheme proposed in this paper is able to detect ship targets in a fast, efficient and robust way.

  6. Project PHARUS: Towards a polarimetric C-band airborne SAR

    NARCIS (Netherlands)

    Hoogeboom, P.; Koomen, P.J.; Otten, M.P.G.; Pouwels, H.; Snoeij, P.

    1989-01-01

    A few years ago three institutes in the Netherlands developed a plan to design and build a polarimetric C-band aircraft SAR system of a novel design, called PHARUS (PHased Array Universal SAR), meant as a replacement for our current digital SLAR system. These institutes are the Physics and

  7. Crop Classification Using Short-Revisit Multitemporal SAR Data

    DEFF Research Database (Denmark)

    Skriver, Henning; Mattia, Francesco; Satalino, Giuseppe

    2011-01-01

    Classification of crops and other land cover types is an important application of both optical/infrared and SAR satellite data. It is already an import application of present satellite systems, as it will be for planned missions, such as the Sentinels. An airborne SAR data set with a short revisi...

  8. INVENTORY OF IRRIGATED RICE ECOSYSTEM USING POLARIMETRIC SAR DATA

    Directory of Open Access Journals (Sweden)

    P. Srikanth

    2012-08-01

    Full Text Available An attempt has been made in the current study to assess the potential of polarimetric SAR data for inventory of kharif rice and the major competing crop like cotton. In the process, physical process of the scattering mechanisms occurring in rice and cotton crops at different phonological stages was studied through the use of temporal Radarsat 2 Fine quadpol SAR data. The temporal dynamics of the volume, double and odd bounce, entropy, anisotropy, alpha parameters and polarimertic signatures, classification through isodata clustering and Wishart techniques were assessed. The Wishart (H-a classification showed higher overall as well as rice and cotton crop accuracies compared to the isodata clustering from Freeman 3-component decomposition. The classification of temporal SAR data sets independently showed that the rice crop forecasting can be advanced with the use of appropriate single date polarimetric SAR data rather than using temporal SAR amplitude data sets with the single polarization in irrigated rice ecosystems

  9. Assessing ScanSAR Interferometry for Deformation Studies

    Science.gov (United States)

    Buckley, S. M.; Gudipati, K.

    2007-12-01

    There is a trend in civil satellite SAR mission design to implement an imaging strategy that incorporates both stripmap mode and ScanSAR imaging. This represents a compromise between high resolution data collection and a desire for greater spatial coverage and more frequent revisit times. However, mixed mode imaging can greatly reduce the number of stripmap images available for measuring subtle ground deformation. Although ScanSAR-ScanSAR and ScanSAR-stripmap repeat-pass interferometry have been demonstrated, these approaches are infrequently used for single interferogram formation and nonexistent for InSAR time series analysis. For future mission design, e.g., a dedicated US InSAR mission, the effect of various ScanSAR system parameter choices on InSAR time series analysis also remains unexplored. Our objective is to determine the utility of ScanSAR differential interferometry. We will demonstrate the use of ScanSAR interferograms for several previous deformation studies: localized and broad-scale urban land subsidence, tunneling, volcanic surface movements and several examples associated with the seismic cycle. We also investigate the effect of various ScanSAR burst synchronization levels on our ability to detect and make quality measurements of deformation. To avoid the issues associated with Envisat ScanSAR burst alignment and to exploit a decade of InSAR measurements, we simulate ScanSAR data by bursting (throwing away range lines of) ERS-1/2 data. All the burst mode datasets are processed using a Modified SPECAN algorithm. To investigate the effects of burst misalignment, a number of cases with varying degrees of burst overlap are considered. In particular, we look at phase decorrelation as a function of percentage of burst overlap. Coherence clearly reduces as the percentage of overlap decreases and we find a useful threshold of 40-70% burst overlap depending on the study site. In order to get a more generalized understanding for different surface conditions

  10. Guided SAR image despeckling with probabilistic non local weights

    Science.gov (United States)

    Gokul, Jithin; Nair, Madhu S.; Rajan, Jeny

    2017-12-01

    SAR images are generally corrupted by granular disturbances called speckle, which makes visual analysis and detail extraction a difficult task. Non Local despeckling techniques with probabilistic similarity has been a recent trend in SAR despeckling. To achieve effective speckle suppression without compromising detail preservation, we propose an improvement for the existing Generalized Guided Filter with Bayesian Non-Local Means (GGF-BNLM) method. The proposed method (Guided SAR Image Despeckling with Probabilistic Non Local Weights) replaces parametric constants based on heuristics in GGF-BNLM method with dynamically derived values based on the image statistics for weight computation. Proposed changes make GGF-BNLM method adaptive and as a result, significant improvement is achieved in terms of performance. Experimental analysis on SAR images shows excellent speckle reduction without compromising feature preservation when compared to GGF-BNLM method. Results are also compared with other state-of-the-art and classic SAR depseckling techniques to demonstrate the effectiveness of the proposed method.

  11. An ML-Based Radial Velocity Estimation Algorithm for Moving Targets in Spaceborne High-Resolution and Wide-Swath SAR Systems

    Directory of Open Access Journals (Sweden)

    Tingting Jin

    2017-04-01

    Full Text Available Multichannel synthetic aperture radar (SAR is a significant breakthrough to the inherent limitation between high-resolution and wide-swath (HRWS compared with conventional SAR. Moving target indication (MTI is an important application of spaceborne HRWS SAR systems. In contrast to previous studies of SAR MTI, the HRWS SAR mainly faces the problem of under-sampled data of each channel, causing single-channel imaging and processing to be infeasible. In this study, the estimation of velocity is equivalent to the estimation of the cone angle according to their relationship. The maximum likelihood (ML based algorithm is proposed to estimate the radial velocity in the existence of Doppler ambiguities. After that, the signal reconstruction and compensation for the phase offset caused by radial velocity are processed for a moving target. Finally, the traditional imaging algorithm is applied to obtain a focused moving target image. Experiments are conducted to evaluate the accuracy and effectiveness of the estimator under different signal-to-noise ratios (SNR. Furthermore, the performance is analyzed with respect to the motion ship that experiences interference due to different distributions of sea clutter. The results verify that the proposed algorithm is accurate and efficient with low computational complexity. This paper aims at providing a solution to the velocity estimation problem in the future HRWS SAR systems with multiple receive channels.

  12. Airborne S-Band SAR for Forest Biophysical Retrieval in Temperate Mixed Forests of the UK

    Directory of Open Access Journals (Sweden)

    Ramesh K. Ningthoujam

    2016-07-01

    Full Text Available Radar backscatter from forest canopies is related to forest cover, canopy structure and aboveground biomass (AGB. The S-band frequency (3.1–3.3 GHz lies between the longer L-band (1–2 GHz and the shorter C-band (5–6 GHz and has been insufficiently studied for forest applications due to limited data availability. In anticipation of the British built NovaSAR-S satellite mission, this study evaluates the benefits of polarimetric S-band SAR for forest biophysical properties. To understand the scattering mechanisms in forest canopies at S-band the Michigan Microwave Canopy Scattering (MIMICS-I radiative transfer model was used. S-band backscatter was found to have high sensitivity to the forest canopy characteristics across all polarisations and incidence angles. This sensitivity originates from ground/trunk interaction as the dominant scattering mechanism related to broadleaved species for co-polarised mode and specific incidence angles. The study was carried out in the temperate mixed forest at Savernake Forest and Wytham Woods in southern England, where airborne S-band SAR imagery and field data are available from the recent AirSAR campaign. Field data from the test sites revealed wide ranges of forest parameters, including average canopy height (6–23 m, diameter at breast-height (7–42 cm, basal area (0.2–56 m2/ha, stem density (20–350 trees/ha and woody biomass density (31–520 t/ha. S-band backscatter-biomass relationships suggest increasing backscatter sensitivity to forest AGB with least error between 90.63 and 99.39 t/ha and coefficient of determination (r2 between 0.42 and 0.47 for the co-polarised channel at 0.25 ha resolution. The conclusion is that S-band SAR data such as from NovaSAR-S is suitable for monitoring forest aboveground biomass less than 100 t/ha at 25 m resolution in low to medium incidence angle range.

  13. Relations of SARS-Related Stressors and Coping to Chinese College Students' Psychological Adjustment during the 2003 Beijing SARS Epidemic

    Science.gov (United States)

    Main, Alexandra; Zhou, Qing; Ma, Yue; Luecken, Linda J.; Liu, Xin

    2011-01-01

    This study examined the main and interactive relations of stressors and coping related to severe acute respiratory syndrome (SARS) with Chinese college students' psychological adjustment (psychological symptoms, perceived general health, and life satisfaction) during the 2003 Beijing SARS epidemic. All the constructs were assessed by self-report…

  14. Modelling of potentially promising SARS protease inhibitors

    International Nuclear Information System (INIS)

    Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof

    2007-01-01

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation

  15. 3D Monitoring of Buildings Using TerraSAR-X InSAR, DInSAR and PolSAR Capacities

    Directory of Open Access Journals (Sweden)

    Flora Weissgerber

    2017-09-01

    Full Text Available The rapid expansion of cities increases the need of urban remote sensing for a large scale monitoring. This paper provides greater understanding of how TerraSAR-X (TSX high-resolution abilities enable to reach the spatial precision required to monitor individual buildings, through the use of a 4 year temporal stack of 100 images over Paris (France. Three different SAR modes are investigated for this purpose. First a method involving a whole time-series is proposed to measure realistic heights of buildings. Then, we show that the small wavelength of TSX makes the interferometric products very sensitive to the ordinary building-deformation, and that daily deformation can be measured over the entire building with a centimetric accuracy, and without any a priori on the deformation evolution, even when neglecting the impact of the atmosphere. Deformations up to 4 cm were estimated for the Eiffel Tower and up to 1 cm for other lower buildings. These deformations were analyzed and validated with weather and in situ local data. Finally, four TSX polarimetric images were used to investigate geometric and dielectric properties of buildings under the deterministic framework. Despite of the resolution loss of this mode, the possibility to estimate the structural elements of a building orientations and their relative complexity in the spatial organization are demonstrated.

  16. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  17. The Ecosystems SAR (EcoSAR) an Airborne P-band Polarimetric InSAR for the Measurement of Vegetation Structure, Biomass and Permafrost

    Science.gov (United States)

    Rincon, Rafael F.; Fatoyinbo, Temilola; Ranson, K. Jon; Osmanoglu, Batuhan; Sun, Guoqing; Deshpande, Manohar D.; Perrine, Martin L.; Du Toit, Cornelis F.; Bonds, Quenton; Beck, Jaclyn; hide

    2014-01-01

    EcoSAR is a new synthetic aperture radar (SAR) instrument being developed at the NASA/ Goddard Space Flight Center (GSFC) for the polarimetric and interferometric measurements of ecosystem structure and biomass. The instrument uses a phased-array beamforming architecture and supports full polarimetric measurements and single pass interferometry. This Instrument development is part of NASA's Earth Science Technology Office Instrument Incubator Program (ESTO IIP).

  18. SARS-CoV related Betacoronavirus and diverse Alphacoronavirus members found in western old-world.

    Science.gov (United States)

    Ar Gouilh, Meriadeg; Puechmaille, Sébastien J; Diancourt, Laure; Vandenbogaert, Mathias; Serra-Cobo, Jordi; Lopez Roïg, Marc; Brown, Paul; Moutou, François; Caro, Valérie; Vabret, Astrid; Manuguerra, Jean-Claude

    2018-04-01

    The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus ferrumequinum were identified. The diversity and prevalence of bat coronaviruses presently reported from western Europe is much higher than previously described and includes a SARS-CoV sister group. This diversity demonstrates the dynamic evolution and circulation of coronaviruses in this species. That said, the identified coronaviruses were consistently associated with a particular bat species or genus, and these relationships were maintained no matter the geographic location. The observed phylogenetic grouping of coronaviruses from the same species in Europe and Asia, emphasizes the role of host/pathogen coevolution in this group. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. SAR in human head model due to resonant wireless power transfer system.

    Science.gov (United States)

    Zhang, Chao; Liu, Guoqiang; Li, Yanhong; Song, Xianjin

    2016-04-29

    Efficient mid-range wireless power transfer between transmitter and the receiver has been achieved based on the magnetic resonant coupling method. The influence of electromagnetic field on the human body due to resonant wireless power transfer system (RWPT) should be taken into account during the design process of the system. To analyze the transfer performance of the RWPT system and the change rules of the specific absorption rate (SAR) in the human head model due to the RWPT system. The circuit-field coupling method for a RWPT system with consideration of the displacement current was presented. The relationship between the spiral coil parameters and transfer performance was studied. The SAR in the human head model was calculated under two different exposure conditions. A system with output power higher than 10 W at 0.2 m distance operating at a frequency of approximately 1 MHz was designed. The FEM simulation results show the peak SAR value is below the safety limit which appeared when the human head model is in front of the transmitter. The simulation results agreed well with the experimental results, which verified the validity of the analysis and design.

  20. Estimation of the Above Ground Biomass of Tropical Forests using Polarimetric and Tomographic SAR Data Acquired at P Band and 3-D Imaging Techniques

    Science.gov (United States)

    Ferro-Famil, L.; El Hajj Chehade, B.; Ho Tong Minh, D.; Tebaldini, S.; LE Toan, T.

    2016-12-01

    Developing and improving methods to monitor forest biomass in space and time is a timely challenge, especially for tropical forests, for which SAR imaging at larger wavelength presents an interesting potential. Nevertheless, directly estimating tropical forest biomass from classical 2-D SAR images may reveal a very complex and ill-conditioned problem, since a SAR echo is composed of numerous contributions, whose features and importance depend on many geophysical parameters, such has ground humidity, roughness, topography… that are not related to biomass. Recent studies showed that SAR modes of diversity, i.e. polarimetric intensity ratios or interferometric phase centers, do not fully resolve this under-determined problem, whereas Pol-InSAR tree height estimates may be related to biomass through allometric relationships, with, in general over tropical forests, significant levels of uncertainty and lack of robustness. In this context, 3-D imaging using SAR tomography represents an appealing solution at larger wavelengths, for which wave penetration properties ensures a high quality mapping of a tropical forest reflectivity in the vertical direction. This paper presents a series of studies led, in the frame of the preparation of the next ESA mission BIOMASS, on the estimation of biomass over a tropical forest in French Guiana, using Polarimetric SAR Tomographic (Pol-TomSAR) data acquired at P band by ONERA. It is then shown that Pol-TomoSAR significantly improves the retrieval of forest above ground biomass (AGB) in a high biomass forest (200 up to 500 t/ha), with an error of only 10% at 1.5-ha resolution using a reflectivity estimates sampled at a predetermined elevation. The robustness of this technique is tested by applying the same approach over another site, and results show a similar relationship between AGB and tomographic reflectivity over both sites. The excellent ability of Pol-TomSAR to retrieve both canopy top heights and ground topography with an error