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Sample records for 2-aminothiazole-4-carboxylate derivatives active

  1. Derivatives Activity at Troubled Banks

    Joe Peek; Rosengren, Eric S.

    1996-01-01

    Derivatives have become an essential instrument for hedging risks, yet moral hazard can lead to their misuse by problem banks. Given that the absence of comprehensive data on bank derivatives activities prevents an accurate assessment of bank risk-taking, banks have an opportunity to take unmonitored second bets. Thus , troubled banks have the motive to increase risk, and derivatives provide the means to do so. The role of bank supervisors should be to limit the opportunity through more compr...

  2. Biological activities of substituted trichostatic acid derivatives

    Cédric Charrier; Joëlle Roche; Jean-Pierre Gesson; Philippe Bertrand

    2009-07-01

    New substituted trichostatic acid derivatives have been synthesized and evaluated for their biological activities towards the H661 non-small lung cancer cell line. These syntheses were achieved by alkylation of propiophenones to introduce the side chain with a terminal precursor of hydroxamic acid and aminobenzamide derivatives. The first fluorinated derivatives of trichostatic acid are described, such as 6-fluoro trichostatin A, with antiproliferative activities in the micromolar range and with histone deacetylase inhibitory activity.

  3. SYNTHESIS AND BIOLOGICAL ACTIVITY OF FURAN DERIVATIVES

    Verma Anupam

    2011-04-01

    Full Text Available Furan derivative are an important class of heterocyclic compound that possess important biological properties. From last few decades a considerable amount of attention has been focussed on synthesis of Furan derivatives and screening them for different pharmacological activities.The furan ring system is the basic skeleton of numerous compounds possessing cardiovascular activities. An iodinated lipophilic furan derivative is widely used in the treatment of ventricular and atrial fibrillation. These moieties are widely employed as antibacterial, antiviral, anti-inflammatory, antifungal, antitumor, Antihyperglycemic, Analgesic, Anticonvulsant etc. Slight change in substitution pattern in furan nucleus causes distinguishable difference in their biological activities. In this review we are discussing about synthesis and various biological activities of newly synthesized furan derivatives.

  4. Diclofenac derivatives with insulin-sensitizing activity

    Jian Ta Wang; Ying Wang; Ji Quan Zhang; Xing Cui; Yi Zhang; Gao Feng Zhu; Lei Tang

    2011-01-01

    A series of diclofenac derivatives were synthesized. The insulin-sensitizing activity of 28 new compounds was evaluated in 3T3-L1 cells. The compounds 10a and 10f exhibited similar insulin-sensitizing activity with positive drag rosiglitazone.

  5. Antifungal activity of ajoene derived from garlic.

    Yoshida, S.(Department of Physics, Chiba University, 263-8522, Chiba, Japan); Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H.; Nakagawa, S

    1987-01-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml.

  6. Anticoagulant activity of original synthetic peptide derivatives.

    Drozd, N N; Tolstenkov, A S; Makarov, V A; Miphtakhova, N T; Voyushina, T L; Sergeev, M E

    2008-01-01

    Original synthetic peptide derivatives exhibit anticoagulant activity in vitro and in vivo. They delayed fibrin clot formation from human blood plasma in tests for the intrinsic coagulation pathway (activated partial thromboplastin time) and final stage of plasma coagulation (thrombin time) and inhibited amidolytic activity of thrombin. We determined the minimum effective dose of the most active compound providing a 2-fold lengthening of blood clotting time (activated partial thromboplastin time test and thrombin time test), which persisted for 2-3 h. PMID:19024001

  7. SYNTHESIS AND BIOLOGICAL ACTIVITY OF PHENOTHIAZINE DERIVATIVES

    Sinha Shweta

    2011-04-01

    Full Text Available Phenothiazines are heterocyclic molecules containing two benzene rings linked in a tricyclic system through nitrogen and sulfur atoms.Phenothiazine derivatives having amino alkyl side chain and these are connected to the nitrogen atom of heterocyclic unit playing crucial role in medicinal chemistry.From last few decades a considerable amount of attention has been focussed on synthesis of phenothiazines derivatives and screening them for different pharmacological activities. The investigation of substituted 10H-Phenothiazines has steadily strong growth because they exhibit a wide range of applications. These moieties are widely employed as antibacterial, antiviral, anti-inflammatory, anticancer, sedatives, tranquilizers agents etc. Slight change in substitution pattern in phenothiazine nucleus causes distinguishable difference in their biological activities. In this review we are discussing about synthesis and various biological activities of newly synthesized Phenothiazine derivatives.

  8. Synthesis and antifungal activity of trichodermin derivatives

    Jing Li Cheng; Yong Zhou; Jin Hao Zhao; Chu Long Zhang; Fu Cheng Lin

    2010-01-01

    A series of derivatives were synthesized from trichodermin(1)which was an antifungal metabolite produced by Trichoderma taxi sp.nov.Their structures were confirmed by 1H NMR,MS spectrum.Their antifungal activities were evaluated in vitro.The preliminary structure activity relationships(SAR)results indicated that the double bond,epoxide moiety and ester group were main pharmacophore elements,the stereochemistry of C4 position played a key role as well,and the compounds 1e-1g displayed stronger antifungal activity against Magnaporthe grisea than 1.

  9. Lithocholic acid and derivatives: Antibacterial activity.

    do Nascimento, Patrícia G G; Lemos, Telma L G; Almeida, Macia C S; de Souza, Juliana M O; Bizerra, Ayla M C; Santiago, Gilvandete M P; da Costa, José G M; Coutinho, Henrique D M

    2015-12-01

    In order to develop bioactive lithocholic acid derivatives, we prepared fifteen semi-synthetic compounds through modification at C-3 and/or C-24. The reactions showed yields ranging from 37% to 100%. The structures of all compounds obtained were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The activity of lithocholic acid and derivatives was evaluated against the growth of Escherichia coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas aeruginosa. The derivative 3α-formyloxy-5β-cholan-24-oic acid (LA-06) showed the best activity, with MIC values of 0.0790 mM against E. coli (Ec 27) and B. cereus in both cases, and 0.0395 mM against S. aureus (ATCC 12692). Lithocholic acid and the derivatives with MIC⩽1.2 mM were evaluated on the susceptibility of some bacterial pathogens to the aminoglycoside antibiotics neomycin, amikacin and gentamicin was evaluated. There are no previously reported studies about these compounds as modifiers of the action of antibiotics or any other drugs. PMID:26216208

  10. Structure-activity relationships of bumetanide derivatives

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

    2015-01-01

    and its derivatives in dogs and their inhibition of hNKCC2A (r(2) = 0.817; P < 0.01). Replacement of the carboxylic group of bumetanide by a non-ionic residue, for example, an anilinomethyl group, decreased inhibition of hNKCC2A, indicating that an acidic group was required for transporter inhibition...... 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...

  11. Thiomorpholine Derivatives with Hypolipidemic and Antioxidant Activity.

    Tooulia, Kyriaki-Konstantina; Theodosis-Nobelos, Panagiotis; Rekka, Eleni A

    2015-09-01

    A number of thiomorpholine derivatives that are structurally similar to some substituted morpholines possessing antioxidant and hypocholesterolemic activity were synthesized. The new compounds incorporate an antioxidant moiety as the thiomorpholine N-substituent. The derivatives were found to inhibit the ferrous/ascorbate-induced lipid peroxidation of microsomal membrane lipids, with IC50 values as low as 7.5 µΜ. In addition, these compounds demonstrate hypocholesterolemic and hypolipidemic action. The most active compound (5) decreases the triglyceride, total cholesterol, and low-density lipoprotein levels in the plasma of Triton WR-1339-induced hyperlipidemic rats, by 80, 78, and 76%, respectively, at 56 mmol/kg (i.p.). They may also act as squalene synthase inhibitors. The above results indicate that the new molecules may be useful as leads for the design of novel compounds as potentially antiatherogenic factors. PMID:26191791

  12. Isocorydine Derivatives and Their Anticancer Activities

    Mei Zhong

    2014-08-01

    Full Text Available In order to improve the anticancer activity of isocorydine (ICD, ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8 and 6a,7-dihydrogen-isocorydione (10 could inhibit the growth of human lung (A549, gastric (SGC7901 and liver (HepG2 cancer cell lines in vitro. Isocorydione (2 could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11, a pro-drug of 8-amino-isocorydine (8, which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.

  13. Antioxidant Activities of 4-Methylumbelliferone Derivatives

    Al-Majedy, Yasameen K.; Al-Amiery, Ahmed A.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2016-01-01

    The synthesis of derivatives of 4-Methylumbelliferone (4-MUs), which are structurally interesting antioxidants, was performed in this study. The modification of 4-Methylumbelliferone (4-MU) by different reaction steps was performed to yield the target compounds, the 4-MUs. The 4-MUs were characterized by different spectroscopic techniques (Fourier transform infrared; FT-IR and Nuclear magnetic resonance; NMR) and micro-elemental analysis (CHNS). The in vitro antioxidant activity of the 4-MUs was evaluated in terms of their free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH), Nitric oxide radical scavenging activity assay, chelating activity and their (FRAP) ferric-reducing antioxidant power, which were compared with a standard antioxidant. Our results reveal that the 4-MUs exhibit excellent radical scavenging activities. The antioxidant mechanisms of the 4-MUs were also studied. Density Function Theory (DFT)-based quantum chemical studies were performed with the basis set at 3-21G. Molecular models of the synthesized compounds were studied to understand the antioxidant activity. The electron levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), for these synthesized antioxidants were also studied. PMID:27243231

  14. Antioxidant Activities of 4-Methylumbelliferone Derivatives.

    Yasameen K Al-Majedy

    Full Text Available The synthesis of derivatives of 4-Methylumbelliferone (4-MUs, which are structurally interesting antioxidants, was performed in this study. The modification of 4-Methylumbelliferone (4-MU by different reaction steps was performed to yield the target compounds, the 4-MUs. The 4-MUs were characterized by different spectroscopic techniques (Fourier transform infrared; FT-IR and Nuclear magnetic resonance; NMR and micro-elemental analysis (CHNS. The in vitro antioxidant activity of the 4-MUs was evaluated in terms of their free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH, Nitric oxide radical scavenging activity assay, chelating activity and their (FRAP ferric-reducing antioxidant power, which were compared with a standard antioxidant. Our results reveal that the 4-MUs exhibit excellent radical scavenging activities. The antioxidant mechanisms of the 4-MUs were also studied. Density Function Theory (DFT-based quantum chemical studies were performed with the basis set at 3-21G. Molecular models of the synthesized compounds were studied to understand the antioxidant activity. The electron levels, namely HOMO (highest occupied molecular orbital and LUMO (lowest unoccupied molecular orbital, for these synthesized antioxidants were also studied.

  15. Cyclic Benzimidazole Derivatives and Their Antitumor Activity

    Karminski-Zamola, G.

    2008-06-01

    Full Text Available Over the past years benzimidazole derivatives are one of the most extensively studied classes of heterocyclic compounds, and have received much attention from synthetic organic as well as medicinal chemists, because of their well known biological activities and their applications in several areas as materials in electronics, in electrochemistry as anticorrosive agents, as polymers or optical materials and fluorescent tags in DNA sequencing. The structure of vitamin B12, as an example, contains a benzimidazole group. Compounds containing benzimidazole nuclei show anticancer, antineoplastic, antiinfective, antibacterial, antifungal and many others activities. Due to the structural similarity of benzimidazole nuclei with some naturally occurring compounds such as purine, they can easily interact with biomolecules of the living systems. The introduction of an additional substituent on the benzimidazole nuclei has been increasing attention in the expectation that such changes could potentially affect the interaction of the molecules with biological targets. Fused cyclic benzimidazole derivatives, as benzimidazo[1,2-a]quinolines,benzimidazo[1,2-c]quinazolines, benzimidazo[2,1-b]isoquinolines and many others, have also interesting biological activities and most of them are very good anticancer agents.DNA is the molecular target of many anticancer drugs in clinical use and development. Compounds which can bind to DNA with intercalative or non-intercalative mechanism play a major role in biological processes such as gene transcription or DNA replication. Benzoannulated benzimidazole analogues contain a planar chromophore and have the ability to become inserted between adjacent base pairs of DNA double helix. Intercalators are recognized as one of the most important classes of anticancer agents. So an understanding of the drug-DNA interactions is a promising approach to developing novel reagents and plays a key role in pharmacology today.

  16. STUDY OF ANTIVIRAL ACTIVITY OF SOME HYDRAZONE PINOSTROBIN DERIVATIVES

    G. K. Mukusheva

    2014-01-01

    Full Text Available New derivatives on the basis of hydrazone pinostrobin molecule were synthesized. Significant antiviral activity of received samples of new hydrazone pinstrobin derivatives was identified.

  17. How are Derivative Accounting Applied for Hedging Activities?

    Doan Van Dinh; Guangming Gong

    2013-01-01

    The derivative instruments accounting plays an important role in the development of the financial instruments markets, commodity market and in the risk management process. Because, the close relationship between the methods of derivative instruments accounting and the derivative instruments in the financial markets, commodity market for hedging activities. Moreover, they bring the relevance and reliability of Financial statements. Application of derivative instruments accounting is an essenti...

  18. Biological activities of water-soluble fullerene derivatives

    Nakamura, S; Mashino, T [Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512 (Japan)], E-mail: mashino-td@pha.keio.ac.jp

    2009-04-01

    Three types of water-soluble fullerene derivatives were synthesized and their biological activities were investigated. C{sub 60}-dimalonic acid, an anionic fullerene derivative, showed antioxidant activity such as quenching of superoxide and relief from growth inhibition of E. coli by paraquat. C{sub 60}-bis(7V,7V-dimethylpyrrolidinium iodide), a cationic fullerene derivative, has antibacterial activity and antiproliferative effect on cancer cell lines. The mechanism is suggested to be respiratory chain inhibition by reactive oxygen species produced by the cationic fullerene derivative. Proline-type fullerene derivatives showed strong inhibition activities on HIV-reverse transcriptase. The IC{sub 50} values were remarkably lower than nevirapine, a clinically used anti-HIV drug. Fullerene derivatives have a big potential for a new type of lead compound to be used as medicine.

  19. Biological activities of water-soluble fullerene derivatives

    Nakamura, S.; Mashino, T.

    2009-04-01

    Three types of water-soluble fullerene derivatives were synthesized and their biological activities were investigated. C60-dimalonic acid, an anionic fullerene derivative, showed antioxidant activity such as quenching of superoxide and relief from growth inhibition of E. coli by paraquat. C60-bis(7V,7V-dimethylpyrrolidinium iodide), a cationic fullerene derivative, has antibacterial activity and antiproliferative effect on cancer cell lines. The mechanism is suggested to be respiratory chain inhibition by reactive oxygen species produced by the cationic fullerene derivative. Proline-type fullerene derivatives showed strong inhibition activities on HIV-reverse transcriptase. The IC50 values were remarkably lower than nevirapine, a clinically used anti-HIV drug. Fullerene derivatives have a big potential for a new type of lead compound to be used as medicine.

  20. Biological activities of water-soluble fullerene derivatives

    Three types of water-soluble fullerene derivatives were synthesized and their biological activities were investigated. C60-dimalonic acid, an anionic fullerene derivative, showed antioxidant activity such as quenching of superoxide and relief from growth inhibition of E. coli by paraquat. C60-bis(7V,7V-dimethylpyrrolidinium iodide), a cationic fullerene derivative, has antibacterial activity and antiproliferative effect on cancer cell lines. The mechanism is suggested to be respiratory chain inhibition by reactive oxygen species produced by the cationic fullerene derivative. Proline-type fullerene derivatives showed strong inhibition activities on HIV-reverse transcriptase. The IC50 values were remarkably lower than nevirapine, a clinically used anti-HIV drug. Fullerene derivatives have a big potential for a new type of lead compound to be used as medicine.

  1. Novel Benzosuberone Derivatives:Synthesis, Characterization and Antibacterial Activity

    J. Venkateswara Rao

    2015-12-01

    Full Text Available The synthesis of novel amide derivatives of benzosuberone 7a-j from commercially available benzosuberone was successfully achieved in six steps. Some of the important reactions that are involved in the synthesis are (i insertion of methylester (ii Suzki reaction and (iii saponification followed by amide bond formation. The newly synthesis benzosuberone derivatives 7a-j were screened for antibacterial activity and the results indicated that in general, benzosuberone derivatives with R = piperazine ring showed good antibacterial activity.

  2. NOVEL ANDROGRAPHOLIDE DERIVATIVES AND THEIR IN VITRO CYTOTOXIC ACTIVITY

    Venkat R. P; Virohit Patil; Ravindra Patil

    2014-01-01

    A new series of sulfonyl-type of andrographolide derivatives were synthesized from andrographolide, the cytotoxic constituent of the plant Andrographis paniculata. The derived analogs (4a-4g) were evaluated for their cytotoxic activity against human small lung cancer (NCI-H187), leukemia K562, breast cancer (MCF-7/ADR) and lung adenocarcinoma (A549) cell lines. Most of the analogues show significant cytotoxic activity against tested cell lines. The methyl sulfonyl derivative 4a had higher act...

  3. NOVEL ANDROGRAPHOLIDE DERIVATIVES AND THEIR IN VITRO CYTOTOXIC ACTIVITY

    Venkat R. P

    2014-05-01

    Full Text Available A new series of sulfonyl-type of andrographolide derivatives were synthesized from andrographolide, the cytotoxic constituent of the plant Andrographis paniculata. The derived analogs (4a-4g were evaluated for their cytotoxic activity against human small lung cancer (NCI-H187, leukemia K562, breast cancer (MCF-7/ADR and lung adenocarcinoma (A549 cell lines. Most of the analogues show significant cytotoxic activity against tested cell lines. The methyl sulfonyl derivative 4a had higher activity than parent compound andrographolide 1, and reduced activity than standard drug cisplatin against tested cell lines.

  4. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Deepa Gupta

    2015-01-01

    Full Text Available Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

  5. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity.

    Gupta, Deepa; Jain, D K

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  6. Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity

    Juan David Guzman

    2014-11-01

    Full Text Available Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  7. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.

    Guzman, Juan David

    2014-01-01

    Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships. PMID:25429559

  8. Synthesis of active nitroguaiacol ether derivatives of streptomycin.

    Abad, J P; Amils, R.

    1990-01-01

    The synthesis, purification, and biological properties of nitroguaiacol ether derivatives of streptomycin and their corresponding radioactive reduced products were examined. These derivatives are biologically active against gram-positive and gram-negative eubacteria and they are also photoreactive because of the presence of the nitroguaiacol group in the molecule. We demonstrated that these derivatives can be used as streptomycin analogs in photoaffinity labeling of the macromolecular structu...

  9. Synthesis and Antiviral Activity of Hydrogenated Ferulic Acid Derivatives

    Can Cui; Zhi-Peng Wang; Xiu-jiang Du; Li-Zhong Wang; Shu-Jing Yu; Xing-Hai Liu; Zheng-Ming Li; Wei-Guang Zhao

    2013-01-01

    A series of hydrogenated ferulic acid amide derivatives 4 were synthesized. The molecular structures of the synthesized compounds were analyzed by H1 NMR and HRMS. The biological activity study showed that some of them displayed excellent protection activity and curative activity against TMV at 500 μg/mL.

  10. Design,Synthesis and Antifungal Activity of Novel Triazole Derivatives

    Chun Quan SHENG; Wan Nian ZHANG; Hai Tao JI; Yun Long SONG; Min ZHANG; You Jun ZHOU; Jia Guo LU; Jü ZHU

    2004-01-01

    Twenty-one 1-(1H-1,2,4-triazolyl)-2-(2,4-diflurophenyl)-3-(4-substituted-1- piperazinyl)-2-propanol derivatives were designed and synthesized,on the basis of the active site of lanosterol 14(-demethylase.In vitro antifungal activities showed that some of the target compounds had higher antifungal activity and broader antifungal spectrum than fluconazole.

  11. Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

    Oee-Sook Park; Jae-Chul Jung

    2009-01-01

    The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

  12. Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

    Oee-Sook Park

    2009-11-01

    Full Text Available The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

  13. FASB Proposes Improved Disclosures for Derivatives and Hedging Activities

    2007-01-01

    @@ The Financial Accounting Standards Board (FASB) today issued a proposal that would provide investors and others with better information about the effects of derivative and hedging activities on a company's financial statements.

  14. Synthesis, characterization and antibacterial activity of new fluorescent chitosan derivatives

    Přichystalová, H.; Almonasy, N.; Abdel-Mohsen, A. M.; Abdel-Rahman, R. M.; Fouda, M. M. G.; Vojtova, L.; Kobera, Libor; Spotz, Z.; Burgert, L.; Jancar, J.

    2014-01-01

    Roč. 65, April (2014), s. 234-240. ISSN 0141-8130 Institutional support: RVO:61389013 Keywords : chitosan derivatives * fluorescence * antibacterial activity Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.858, year: 2014

  15. SYNTHESIS AND BIOLOGICAL ACTIVITY OF AMIDE DERIVATIVES OF GINKGOLIDE A

    LI-HONG HU; ZHONG-LIANG CHEN; YU-YUAN XIE

    2001-01-01

    Amide derivatives of ginkgolide A were prepared and evaluated for their in vitro ability to inhibit the PAF-induced aggregation of rabbit platelets. They showed less activities than their parent compound ginkgolide A.

  16. A Framework for the Surveillance of Derivatives Activities

    Eva Gutierrez

    2005-01-01

    This paper proposes a framework for the surveillance of financial institutions' derivatives activities. The designed framework builds on information likely to be collected by financial market regulators for supervisory purposes, and/or information collected by market participants for the purpose of their own risk management. The framework involves four pillars: (i) analyzing quantitative information on Derivatives activities, (ii) determining the adequacy of prudential regulations and supervi...

  17. BIOLOGICAL ACTIVITIES OF OXAZINE AND ITS DERIVATIVES: A REVIEW

    SINDHU T J

    2014-12-01

    Full Text Available Oxazine derivatives are an important class of heterocycles, which has attracted much synthetic interest due to their wide range of biological activities. Oxazine is a heterocyclic compound can be formally derived from benzene, and its reduction products, by suitable substitution of carbon (and hydrogen atoms by nitrogen and oxygen. In the last few years oxazine derivatives have proved to be valuable synthetic intermediates and also possess important biological activities like sedative, analgesic, antipyretic, anticonvulsant, antitubercular, antitumour, antimalarial and antimicrobial. In these days, development of drug resistance is a major problem and to overcome this situation, it is necessary to synthesize new classes of compounds. The aim of the article is to review the generalization of the collected data about the synthesis of oxazine derivatives and their activities. We hope that this work will be a definite interest for researchers concerned with azines in generally and oxazines in particular.

  18. Synthesis and antimicrobial activity of amphiphilic carbohydrate derivatives

    N-monoalkylated diamines were synthesised and treated with D-ribonolactone or D-gluconolactone. The resulting aldonamides were evaluated for their antimicrobial activity against S. aureus, E. coli, M. tuberculosis and C. albicans. Two hydrazides were also prepared from ribonohydrazide and their biological activity was compared to their amide analogues. All the ribono-derivatives displayed moderated antitubercular activity, and some of them were also active against S. aureus. (author)

  19. [Antifungal activity of 5-benzilidene pyrrolone and furanone derivatives].

    de Carvalho, M G; Pitta, I da R; Galdino, S L; Takaki, G de C; Bergé, G

    1989-01-01

    The antifungal activity against Neurospora crassa of some 5-benzilidene pyrrolone and furanone derivatives was realised. Relations between the structure and this biological activity are established with Fujita-Ban and Hansch methods. The preponderant part of lipophilicity, resonance effect and E or Z configurations have been showed. PMID:2535109

  20. Synthesis of monomethylated dioscin derivatives and their antitumor activities.

    Li, Ming; Han, Xiuwen; Yu, Biao

    2003-01-20

    All possible eight monomethylated dioscin derivatives (1-8) were synthesized. Their inhibitory activities against P388 and A-549 cells were determined, and the results indicate that six of the eight hydroxyls of dioscin are the 'key polar groupings' for tumor inhibitory activities. PMID:12526835

  1. Synthesis and Anticancer Activity of Novel Thiazole-5-Carboxamide Derivatives

    Wen-Xi Cai

    2016-01-01

    Full Text Available A series of novel 2-phenyl-4-trifluoromethyl thiazole-5-carboxamide derivatives have been synthesized and evaluated for their anticancer activity against A-549, Bel7402, and HCT-8 cell lines. Among the tested compounds, highest activity (48% was achieved with the 4-chloro-2-methylphenyl amido substituted thiazole containing the 2-chlorophenyl group on the two position of the heterocyclic ring. Other structurally similar compounds displayed moderate activity. The key intermediates have been fully characterized.

  2. Synthesis and anticancer activity of novel fluorinated asiatic acid derivatives.

    Gonçalves, Bruno M F; Salvador, Jorge A R; Marín, Silvia; Cascante, Marta

    2016-05-23

    A series of novel fluorinated Asiatic Acid (AA) derivatives were successfully synthesized, tested for their antiproliferative activity against HeLa and HT-29 cell lines, and their structure activity relationships were evaluated. The great majority of fluorinated derivatives showed stronger antiproliferative activity than AA in a concentration dependent manner. The most active compounds have a pentameric A-ring containing an α,β-unsaturated carbonyl group. The compounds with better cytotoxic activity were then evaluated against MCF-7, Jurkat, PC-3, A375, MIA PaCa-2 and BJ cell lines. Derivative 14 proved to be the most active compound among all tested derivatives and its mechanism of action was further investigated in HeLa cell line. The results showed that compound 14 induced cell cycle arrest in G0/G1 stage as a consequence of up-regulation of p21(cip1/waf1) and p27(kip1) and down-regulation of cyclin D3 and Cyclin E. Furthermore, compound 14 was found to induce caspase driven-apoptosis with activation of caspases-8 and caspase-3 and the cleavage of PARP. The cleavage of Bid into t-Bid, the up-regulation of Bax and the down-regulation of Bcl-2 were also observed after treatment of HeLa cells with compound 14. Taken together, these mechanistic studies revealed the involvement of extrinsic and intrinsic pathways in the apoptotic process induced by compound 14. Importantly, the antiproliferative activity of this compound on the non-tumor BJ human fibroblast cell line is weaker than in the tested cancer cell lines. The enhanced potency (between 45 and 90-fold more active than AA in a panel of cancer cell lines) and selectivity of this new AA derivative warrant further preclinical evaluation. PMID:26974379

  3. Synthesis and antitumor activity of natural compound aloe emodin derivatives.

    Thimmegowda, Naraganahalli R; Park, Chanmi; Shwetha, Bettaswamigowda; Sakchaisri, Krisada; Liu, Kangdong; Hwang, Joonsung; Lee, Sangku; Jeong, Sook J; Soung, Nak K; Jang, Jae H; Ryoo, In-Ja; Ahn, Jong S; Erikson, Raymond L; Kim, Bo Y

    2015-05-01

    In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a-j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure-activity relationships. The structures of the compounds were determined by (1) H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI-H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations. PMID:25323822

  4. Synthesis, structure and biological properties of active spirohydantoin derivatives

    Lazić Anita M.

    2016-01-01

    Full Text Available Spirohidantoins represent an pharmacologically important class of heterocycles since many derivatives have been recognized that display interesting activities against a wide range of biological targets. First synthesis of cycloalkanespiro-5-hydantoins was performed by Bucherer and Lieb 1934 by the reaction of cycloalkanone, potassium cyanide and ammonium-carbonate at reflux in a mixture of ethanol and water. QSAR (Quantitative Structure-Activity Relationship studies showed that a wide range of biological activities of spirohydantoin derivatives strongly depend upon their structure. This paper describes different methods of synthesis of spirohydantoin derivatives, their physico-chemical properties and biological activity. It emphasizes the importance of cycloalkanespiro-5-hydantoins with anticonvulsant, antiproliferative, antipsychotic, antimicrobial and antiinflammatory properties as well as their importance in the treatment of diabetes. Numerous spirohydantoin compounds exhibit physiological activity such as serotonin and fibrinogen antagonist, inhibitors of the glycine binding site of the NMDA receptor also, antagonist of leukocyte cell adhesion, acting as allosteric inhibitors of the protein-protein interactions. Some spirohydantoin derivatives have been identified as antitumor agents. Their activity depends on the substituent presented at position N-3 of the hydantoin ring and increases in order alkene > ester > ether. Besides that, compounds that contain two electron withdrawing groups (e.g. fluorine or chlorine on the third and fourth position of the phenyl ring are better antitumor agents than compounds with a single electron withdrawing group. [Projekat Ministarstva nauke Republike Srbije, br. 172013

  5. Synthesis and antitumour activity of 4-aminoquinazoline derivatives

    Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

    2016-07-01

    Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

  6. Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives.

    El-Nassan, Hala Bakr

    2015-04-01

    The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24 nM/mL. PMID:24899376

  7. Synthesis and Antimicrobial Activities of Some Novel Quinoxalinone Derivatives

    Y. A. Ammar

    2000-06-01

    Full Text Available Condensation of 4-benzoyl-1,2-phenylenediamine with sodium pyruvate in acetic acid furnished two products which were identified as 6-benzoyl and 7-benzoyl-3-methyl-2(1Hquinoxalinones (1a,b. Fusion of 1a with aromatic aldehydes furnished the styryl derivatives 2a-c. Alkylation of 1a,b with dimethyl sulphate or ethyl chloroacetate produced the N-alkyl derivatives 3a,b and 4a,b. Hydrazinolysis of the ester derivative 4a with hydrazine hydrate afforded the hydrazide derivative 5 which underwent condensation with aldehydes to give the corresponding hydrazone derivatives 6a,b. In addition, chlorination of 1a with thionyl chloride afforded the 2-chloro derivative 7 which was subjected to reaction with sodium azide and n-butylamine to yield the corresponding tetrazolo (8 and n-butylamino (9 derivatives, respectively. The structures of the compounds prepared were confirmed by analytical and spectral data. Also, some of the synthesized compounds were screened for antimicrobial activity.

  8. Synthesis, antimicrobial and antioxidative activity of some new isatin derivatives

    Šekularac Gavrilo M.

    2014-01-01

    Full Text Available The isatin derivatives, Schiff bases, were synthesized by the reaction of isatin and various substituted primary amines and characterized by several spectroscopic methods. Investigation of the antimicrobial activity of the synthesized compounds was performed by the agar dilution method, against different strains of bacteria and one fungi. The antioxidative activity of the synthesized compounds was also determined. Some of the compounds have shown the significant activity against the selected strains of microorganisms and the antioxidative activity. [Projekat Ministarstva nauke Republike Srbije, br. 172013 i III 46010

  9. Synthesis and evaluation of antimalarial activity of curcumin derivatives

    ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC50 values ranging from 1.7 to 15.2 μg mL-1), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

  10. Synthesis and activities of new 4-hydroxybenzoxazolone derivatives

    2010-01-01

    A series of new 4-substituted benzoxazolone derivatives were synthesized according to a convenient method,their anti-inflammatory and analgesic activities in vivo were evaluated.All of them were new compounds,the structures of all the synthesized compounds were confirmed by ~1H NMR,~(13)C NMR,ESI-MS and HR-MS.Most of the compounds exhibited anti-inflammatory activity.

  11. The Antibacterial Activity of Honey Derived from Australian Flora

    Irish, Julie; Blair, Shona; Carter, Dee A.

    2011-01-01

    Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A ...

  12. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Deepa Gupta; Jain, D. K.

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antif...

  13. Synthesis and cytotoxic activity of 7-alkynyl camptothecin derivatives

    Feng Xiao; Yadong Xue; Yu Luo; Bo Zhang; Wei Lu; Bo Yang

    2009-01-01

    Several 7-alkynyl camptothecin derivatives were prepared via Sonogashira coupling.And anti-tumor activities of these compounds were evaluated against human esophageal cancer cell line (Eca-109),human chronic myeloid leukaemia cell line (K562),bladder cancer cell line (5637) and gastric cell line (SGC7901).Compounds 9a-d and 10a exhibited remarkable in vitro cytotoxic activity,compared with topotecan.

  14. Synthesis of Olaparib Derivatives and Their Antitumor Activities

    LOU Xi-yu; YANG Xuan; DING Yi-li; WANG Jian-jun; YAN Qing-yan; HUANG Xian-gui; GUO Yang-hui

    2013-01-01

    A series of Olaparib derivatives was synthesized,and their structures were confirmed by 1H NMR,MS and elemental analysis.Their antitumor activities on breast cancer susceptbility gene 1/2(BRCA1/2)-deficient cancer cell lines including HCC1937,Capan-1 and MDA-MB-436 were evaluated.The antitumor activity of compound Olaparib-1 was better than the positive control Olaparib in BRCAl-deficient cell line HCC1937.

  15. Enhanced Antioxidant Activities of Metal Conjugates of Curcumin Derivatives

    Dutta, Sabari; Murugkar, Anupa; Gandhe, Nitasha; Padhye, Subhash

    2001-01-01

    Antioxidant properties of three Curcumin derivatives in which the 1,3-diketone system is appended with nitrogen and sulfur donors and their copper conjugates are examined for the first time. Metal conjugation seems to offer distinct advantages in radical scavenging activities of curcumin compounds.

  16. Polyphenol derivatives inhibit human neutrophil activity by suppressing oxidative burst

    Drábiková, K.; Perečko, T.; Nosáľ, R.; Harmatha, Juraj; Šmidrkal, J.; Jančinová, V.

    2012-01-01

    Roč. 5, Suppl.1 (2012), s. 31-31. ISSN 1337-6853. [Interdisciplinary Toxicological Conference & Advanced Toxicological Course /17./. 27.08.2012-31.08.2012, Stará Lesná] Institutional research plan: CEZ:AV0Z40550506 Keywords : polyphenol derivatives * neutrophil activity * pinosylvin Subject RIV: CC - Organic Chemistry

  17. Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

    Nisachon Khunnawutmanotham; Nitirat Chimnoi; Arunee Thitithanyanont; Patchreenart Saparpakorn; Kiattawee Choowongkomon; Pornpan Pungpo; Supa Hannongbua; Supanna Techasakul

    2009-01-01

    Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wild-type and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT.

  18. Insecticidal and Nematicidal Activities of Novel Mimosine Derivatives

    Binh Cao Quan Nguyen

    2015-09-01

    Full Text Available Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal and nematicidal activities of novel mimosine derivatives. Interestingly, mimosinol and deuterated mimosinol (D-mimosinol from mimosine had strong insecticidal activity which could be a result of tyrosinase inhibition (IC50 = 31.4 and 46.1 μM, respectively. Of synthesized phosphoramidothionate derivatives from two these amino alcohols, two compounds (1a and 1b showed high insecticidal activity (LD50 = 0.5 and 0.7 μg/insect, respectively with 50%–60% mortality at 50 μg/mL which may be attributed to acetylcholinesterase inhibition. Compounds 1a and 1b also had strong nematicidal activity with IC50 = 31.8 and 50.2 μM, respectively. Our results suggest that the length of the alkyl chain and the functional group at the C5-position of phosphoramidothionates derived from mimosinol and d-mimosinol are essential for the insecticidal and nematicidal activities. These results reveal an unexplored scaffold as new insecticide and nematicide.

  19. Synthesis and trypanocidal activity of novel benzimidazole derivatives.

    Velázquez-López, José Miguel; Hernández-Campos, Alicia; Yépez-Mulia, Lilián; Téllez-Valencia, Alfredo; Flores-Carrillo, Paulina; Nieto-Meneses, Rocío; Castillo, Rafael

    2016-09-01

    The present work reports the synthesis and biological activity of a series of 14 benzimidazole derivatives designed to act on the enzyme triosephosphate isomerase of Trypanosoma cruzi (TcTIM). This enzyme is involved in the metabolism of glucose, the only source of energy for the parasite. In this study, we found four compounds that inhibit TcTIM moderately and lack inhibitory activity against human TIM (HsTIM). In vitro studies against T. cruzi epimastigotes showed two compounds that were more active than the reference drug nifurtimox, and these presented a low cytotoxic effect in mouse macrophages (J744 cell line). PMID:27503677

  20. Synthesis, antioxidant and DNA cleavage activities of novel indole derivatives.

    Biradar, J S; Sasidhar, B S; Parveen, R

    2010-09-01

    A new series of novel indole derivatives containing barbitone moiety (5a-i) are synthesized by simple and efficient condensation of chalcones (3a-i) with barbituric acid (4). The synthesized compounds are screened for their antioxidant (free radical scavenging, total antioxidant capacity and ferric reducing antioxidant power) and DNA cleavage activities were evaluated. Among the synthesized compounds (5a), (5d) and (5g) exhibited excellent antioxidant activity and all the tested compounds in the series have exhibited promising DNA cleavage activities. The structures of the synthesized compounds are assigned on the basis of elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. PMID:20594623

  1. Summary of diamino pyrazoles derived and study their biological activities

    The work involves the synthesis of new heterocyclic structures diamino pyrazoles derivatives that are present in many natural products and products of pharmacological and therapeutic interests and study their biological activities. In order to develop a radiotracer interest and use in diagnostic nuclear medicine, we are interested to synthesis a pyrazole derivative with the precursor [Re(CO)5Br] and studying the antibacterial and antifungal activity of 3.5-diamino pyrazole and even thioamide complex rhenium. The objectives of our workout: 1/ Synthesis of molecules 3,5-diamino pyrazole and thioamide. 2/ Synthesis of 3,5-diamino pyrazole-rhenium complex. 3/ The in vitro study: Bacteriological Tests (Study of antibacterial and antifungal activity of 3,5-diamino pyrazole and thioamide). The first part of this work concerns the chemical synthesis of molecules such as: thioamide, Amp z1 Ampz2 and then we had synthesized the complex 3,5-diamino pyrazole-rhenium. Similarly we determined the physicochemical characteristics of the compounds synthesized by CLHP, CCM and RMN (1H, 13C). The second part is devoted to the study in vitro of biological activities of the synthesized molecules and complex 3,5 diaminopyrazole-rhenium with concentration 1 mg/mL and 2 mg/mL. The results allow us to say that the thioamide and Ampz2 have antibacterial activity against S. enterica and Ampz2 has low activity against S. aureus and P. aeruginossa. Other pyrazole derivatives have no significant antibacterial and antifungal activity. The results also show that the synthesized compounds of concentration 2 mg/mL in relation to the inhibition zones of amoxicillin and DMSO: 1/ Escherichia coli, there is antibacterial activity for thioamide, and the Amp z1-Re Ampz2 compound. 2/ Staphylococcus aureus, the complex Ampz 1-Re and the thioamide have significant antibacterial activity. 3/ Salmonella, we observe that the thioamide molecules, Ampz2 and Amp z1-Re have significant antibacterial activity while

  2. ANTIMICROBIAL ACTIVITY OF EUGENOL DERIVATIVES Antimikrobielle Aktivität EUGENOL DERIVATE

    George Eyambe, Luis Canales and Bimal K. Banik

    2011-01-01

    The antibacterial properties of the clove plant are due to the presence of eugenol, an aromatic phenolic compound. Eugenol was isolated from clove by stem distillation. The alkene group in eugenol was epoxidized resulting in the synthesis of epoxide-eugenol. The heterocyclic ring in epoxide was cleaved to a bromoalcohol derivative. The compounds synthesized epoxideeugenol, bromo alcohol and euginol were tested for antimicrobial activity against Staphylococcus aureus (ATCC 25923). Epoxide-euge...

  3. Synthesis and photobiological activity of new methylpsoralen derivatives.

    Gia, O; Uriarte, E; Zagotto, G; Baccichetti, F; Antonello, C; Marciani-Magno, S

    1992-06-30

    The synthesis and the photobiological activity of two new derivatives of psoralen (3,4'-dimethylpsoralen and 3,4',8-trimethylpsoralen) has been described. They are congeners of the monofunctional linear furocoumarin 3,4'-dimethyl-8-methoxypsoralen. Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8. The number of photolesions is linearly related to adenine-thymine content of the nucleic acid which indicates lack of specificity for particular sequences of the nucleic acid. The structural arrangement of DNA (single stranded, double stranded, nucleosomes and chromatin) plays an additional role in affecting the photobinding process. Unlike their 8-methoxy congener the new derivatives cross-link DNA to a substantial extent. Their photobiological properties, including erythema formation, reflect very closely those of 8-methoxypsoralen (8-MOP). The conclusion can be drawn that 3,4'-dimethyl-8-MOP represents a unique derivative in its family. PMID:1432387

  4. Adsorption Properties of Lignin-derived Activated Carbon Fibers (LACF)

    Contescu, Cristian I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gallego, Nidia C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thibaud-Erkey, Catherine [United Technologies Research Center (UTRC), East Hartford, CT (United States); Karra, Reddy [United Technologies Research Center (UTRC), East Hartford, CT (United States)

    2016-04-01

    The object of this CRADA project between Oak Ridge National Laboratory (ORNL) and United Technologies Research Center (UTRC) is the characterization of lignin-derived activated carbon fibers (LACF) and determination of their adsorption properties for volatile organic compounds (VOC). Carbon fibers from lignin raw materials were manufactured at Oak Ridge National Laboratory (ORNL) using the technology previously developed at ORNL. These fibers were physically activated at ORNL using various activation conditions, and their surface area and pore-size distribution were characterized by gas adsorption. Based on these properties, ORNL did down-select five differently activated LACF materials that were delivered to UTRC for measurement of VOC adsorption properties. UTRC used standard techniques based on breakthrough curves to measure and determine the adsorption properties of indoor air pollutants (IAP) - namely formaldehyde and carbon dioxide - and to verify the extent of saturated fiber regenerability by thermal treatments. The results are summarized as follows: (1) ORNL demonstrated that physical activation of lignin-derived carbon fibers can be tailored to obtain LACF with surface areas and pore size distributions matching the properties of activated carbon fibers obtained from more expensive, fossil-fuel precursors; (2) UTRC investigated the LACF potential for use in air cleaning applications currently pursued by UTRC, such as building ventilation, and demonstrated their regenerability for CO2 and formaldehyde, (3) Both partners agree that LACF have potential for possible use in air cleaning applications.

  5. Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

    Silva, M.S.S.; Lima, S.G. de; Lopes, J.A.D.; Chaves, M.H.; Cito, A.M.G.L. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Quimica]. E-mail: gracito@ufpi.br; Oliveira, E.H. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Microbiologia e Parasitologia; Reis, F.A.M. [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Inst. de Quimica

    2008-07-01

    Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by {sup 1}H and {sup 13}C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), mono ene anacardic acid (3), alpha-amirine (4), beta-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp. (author)

  6. Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

    Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by 1H and 13C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), mono ene anacardic acid (3), alpha-amirine (4), beta-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp. (author)

  7. Recent insight into the biological activities of synthetic xanthone derivatives.

    Shagufta; Ahmad, Irshad

    2016-06-30

    Xanthones are a class of oxygen containing heterocyclic compounds with a broad range of biological activities, and they have prominent significance in the field of medicinal chemistry. Xanthone is an attractive scaffold for the design and development of new drugs due to its promising biological activities, primarily as anticancer, antimalarial, antimicrobial, anti-HIV, anticonvulsant, anticholinesterase, antioxidant, anti-inflammatory, and as inhibitors of several enzymes like α-glycosidase, topoisomerase, protein kinase, aromatase, etc. In this review, we have compiled and discussed recent developments on the pharmacological profile of synthetic xanthone derivatives for different therapeutic targets. The review highlights the therapeutic significance of xanthones and offers support in the development of new xanthone derivatives as therapeutic agents. PMID:27111599

  8. Anti-cancer activities of diospyrin, its derivatives and analogues

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  9. Synthesis, characterization, and antifungal activity of novel quaternary chitosan derivatives.

    Li, Rongchun; Guo, Zhanyong; Jiang, Pingan

    2010-09-01

    Three novel quaternary chitosan derivatives were successfully synthesized by reaction of chloracetyl chitosan (CACS) with pyridine (PACS), 4-(5-chloro-2-hydroxybenzylideneamino)-pyridine (CHPACS), and 4-(5-bromo-2-hydroxybenzylideneamino)-pyridine (BHPACS). The chemical structure of the prepared chitosan derivatives was confirmed by Fourier transform infrared (FT-IR) and (13)C nuclear magnetic resonance ((13)C NMR) and their antifungal activity against Cladosporium cucumerinum, Monilinia fructicola, Colletotrichum lagenarium, and Fusarium oxysporum was assessed. Comparing with the antifungal activity of chitosan, CACS, and PACS, CHPACS and BHPACS exhibited obviously better inhibitory effects, which should be related to the synergistic reaction of chitosan itself with the grafted 2-[4-(5-chloro-2-hydroxybenzylideneamino)-pyridyl]acetyl and 2-[4-(5-bromo-2-hydroxybenzylideneamino)-pyridyl]acetyl. PMID:20615498

  10. Vibrational spectra, structure and antioxidant activity of gossypol imine derivatives

    Ilkevych, N. S.; Schroeder, G.; Rybachenko, V. I.; Chotiy, K. Y.; Makarova, R. A.

    2012-02-01

    The structures and tautomeric equilibria of natural polyphenol gossypol and four its imine derivatives were studied by FT-IR-, NMR-spectroscopy and quantum chemistry methods. It was shown that gossypol Schiff bases exist in solution as enamine-enamine tautomer and hydrazones as imine-imine tautomer. Infrared absorption spectra of studied compounds were simulated using the PM3 method. The fundamental vibrational frequencies were evaluated using various scale factors which yield a good agreement between observed and calculated frequencies. Free radical scavenging activity of gossypol and its imine derivatives was evaluated using DPPH method. Antioxidant activity of studied compounds was characterized. Gossypol hydrazones were shown to be more efficient, while Schiff base to be less efficient as antioxidants in comparison with gossypol itself.

  11. Exosomes from myeloid derived suppressor cells carry biologically active proteins

    Burke, Meghan; Choksawangkarn, Waeowalee; Edwards, Nathan; Ostrand-Rosenberg, Suzanne; Fenselau, Catherine

    2013-01-01

    Myeloid-derived suppressor cells (MDSC) are present in most cancer patients where they inhibit natural anti-tumor immunity and are an obstacle to anti-cancer immunotherapies. They mediate immune suppression through their production of proteins and soluble mediators that prevent the activation of tumor-reactive T lymphyocytes, polarize macrophages towards a tumor-promoting phenotype, and facilitate angiogenesis. The accumulation and suppressive potency of MDSC is regulated by inflammation with...

  12. In Silico Antitubercular Activity Analysis of Benzofuran and Naphthofuran Derivatives

    Prashantha Karunakar

    2014-01-01

    Full Text Available For the human health, Mycobacterium tuberculosis (MTB is the deadliest enemy since decades due to its multidrug resistant strains. During latent stage of tuberculosis infection, MTB consumes nitrate as the alternate mechanism of respiration in the absence of oxygen, thus increasing its survival and virulence. NarL is a nitrate/nitrite response transcriptional regulatory protein of two-component signal transduction system which regulates nitrate reductase and formate dehydrogenase for MTB adaptation to anaerobic condition. Phosphorylation by sensor kinase (NarX is the primary mechanism behind the activation of NarL although many response regulators get activated by small molecule phospho-donors in the absence of sensor kinase. Using in silico approach, the molecular docking of benzofuran and naphthofuran derivatives and dynamic study of benzofuran derivative were performed. It was observed that compound Ethyl 5-bromo-3-ethoxycarbonylamino-1-benzofuran-2-carboxylate could be stabilized at the active site for over 10 ns of simulation. Here we suggest that derivatives of benzofuran moiety can lead to developing novel antituberculosis drugs.

  13. In silico antitubercular activity analysis of benzofuran and naphthofuran derivatives.

    Karunakar, Prashantha; Girija, Chamarahalli Ramakrishnaiyer; Krishnamurthy, Venkatappa; Krishna, Venkatarangaiah; Shivakumar, Kunigal Venugopal

    2014-01-01

    For the human health, Mycobacterium tuberculosis (MTB) is the deadliest enemy since decades due to its multidrug resistant strains. During latent stage of tuberculosis infection, MTB consumes nitrate as the alternate mechanism of respiration in the absence of oxygen, thus increasing its survival and virulence. NarL is a nitrate/nitrite response transcriptional regulatory protein of two-component signal transduction system which regulates nitrate reductase and formate dehydrogenase for MTB adaptation to anaerobic condition. Phosphorylation by sensor kinase (NarX) is the primary mechanism behind the activation of NarL although many response regulators get activated by small molecule phospho-donors in the absence of sensor kinase. Using in silico approach, the molecular docking of benzofuran and naphthofuran derivatives and dynamic study of benzofuran derivative were performed. It was observed that compound Ethyl 5-bromo-3-ethoxycarbonylamino-1-benzofuran-2-carboxylate could be stabilized at the active site for over 10 ns of simulation. Here we suggest that derivatives of benzofuran moiety can lead to developing novel antituberculosis drugs. PMID:25302118

  14. Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

    Mireille Fouillaud

    2016-03-01

    Full Text Available Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances.

  15. Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities.

    Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

    2016-04-01

    Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi's productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances. PMID:27023571

  16. Thrombin-specific inactivation of endothelial cell derived plasminogen activator

    Although thrombin (T) has diverse functions in the overall hemostatic mechanism, relatively little is known about its direct effect on components of the fibrinolytic enzyme system. The authors have investigated the interaction of T with plasminogen activators (PA) derived from bovine aortic endothelial cells (EC) in culture (2-5th passage, preconfluent monolayers). Varying concentrations of purified bovine or human thrombin were added to EC-conditioned media (CM). CM + T mixtures were assayed at various times for PA activity using purified plasminogen and a sensitive 125I-fibrinogenolytic or caseinolytic assay. T (5 nM), but not plasmin or trypsin at equivalent concentrations, resulted in a time-dependent inhibition of the PA activity in CM. T had no effect on the PA activity of urokinase, streptokinase or preformed plasmin. The ability of T to inactivate the EC-derived PA was abolished by prior treatment of T with active site-directed reagents. SDS-PAGE and zymography with copolymerized fibrinogen and plasminogen revealed further specificity in that only one of the multiple-molecular weight forms of PA present in EC-CM was inactivated by T. The authors conclude that in a highly specific fashion, T inactivates the predominant PA present in EC-CM by limited proteolysis. Thus, another potentially important function of T is suggested which may have particular significance in the temporal regulation of coagulation and fibrinolysis at the blood-endothelium interface

  17. Design, Synthesis and Fungicidal Activities of Some Novel Pyrazole Derivatives

    Xue-Ru Liu

    2014-09-01

    Full Text Available In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS, and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank Donk, Fusarium oxysporum (S-chl f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27–32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.

  18. Phosphine derivatives of sparfloxacin - Synthesis, structures and in vitro activity

    Komarnicka, Urszula K.; Starosta, Radosław; Guz-Regner, Katarzyna; Bugla-Płoskońska, Gabriela; Kyzioł, Agnieszka; Jeżowska-Bojczuk, Małgorzata

    2015-09-01

    We synthesized two derivatives of sparfloxacin (HSf): aminomethyl(diphenyl)phosphine (PSf) and its oxide (OPSf). The compounds were characterized by NMR spectroscopy, MS and elemental analysis. In addition, the molecular structures of the compounds were determined using DFT and X-ray (OPSf) analysis. The antibacterial activity of HSf and both derivatives was tested against four reference and fifteen clinical Gram-positive and Gram-negative strains of bacteria (sensitive or resistant to fluoroquinolones). The results showed that the activity of PSf was similar to or higher than the activity of HSf, while OPSf was found significantly less active. The compounds were also tested in vitro toward the following cancer cell lines: mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). Regardless of the cancer cell line, derivatization of HSf resulted in the gradual increase of cytotoxicity. OPSf exhibited the highest one (4 h - incubation time: IC50(CT26) = 51.0 ± 1.2; IC50(A549) = 74.9 ± 1.4 and 24 h: IC50(CT26) = 109.2 ± 8.8; IC50(A549) = 52.7 ± 9.2).

  19. Effects of MCI-186 upon neutrophil-derived active oxygens.

    Sumitomo, K; Shishido, N; Aizawa, H; Hasebe, N; Kikuchi, K; Nakamura, M

    2007-01-01

    Reactions of 3-methyl-1-phenyl-2-pyrazoline-5-one (MCI-186) with hypochlorous acid and superoxide were analysed by spectrophotometry and mass spectrometry. The results were applied to the neutrophil system to evaluate the scavenging activity of neutrophil-derived active oxygen species by MCI-186. MCI-186 reacted rapidly with hypochlorous acid (1 x 10(6) M(-1)s(-1)) to form a chlorinated intermediate, followed by a slow conversion to a new spectrum. MCI-186 consumed 3 moles of hypochlorous acid and did not react with superoxide. The newly synthesized fluorescence probes, 2-[6-(4'-amino)-phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (APF) and 2-[6-(4'-hydroxy)phenoxy-3H-anthen-3-on-9-yl]benzoic acid (HPF) successfully detected neutrophil-derived active oxygens (Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 2003; 278: 3170-3175). The rate constants for the reaction of hypochlorous acid with MCI-186 and fluorescence probes was in the order of MCI-186 > APF > HPF. Fluorescence due to the oxidation of APF and HPF was observed with the stimulated neutrophils. The result that the intensity from APF oxidation was higher than that from HPF oxidation is compatible with reports that APF selectively reacts with hypochlorous acid. Fluorescence due to oxidation of both APF and HPF decreased when the reactions were carried out in the presence of a fluorescence probe and MCI-186 in a dose-dependent manner. These results indicate that MCI-186 effectively scavenges neutrophil-derived hypochlorous acid and other active oxygens. PMID:17705989

  20. Synthesis and evaluation of the antiplasmodial activity of tryptanthrin derivatives

    Liliane Abodo Onambele

    2015-08-01

    Full Text Available Malaria remains one of the most deadly diseases threatening humankind and is still affecting a significant proportion of the world population, especially in Africa. Chemotherapy is a vital component of the fight against the disease and new antimalarial agents are urgently needed to curb the spread of malaria parasites that are resistant to existing drugs. The natural product tryptanthrin is known for its wide range of activities, including antiplasmodial activity, but its poor solubility has undermined its development as potent antimicrobial and antiprotozoan agent. The aim of this work was to synthesize analogues of tryptanthrin and to evaluate their antiplasmodial activity against the asexual and sexual blood stages of Plasmodium falciparum. Our results suggest that most tryptanthrin analogues retained their antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30–100 nM. The antiplasmodial activity of the most active compound NT1 (IC50: 30 nM; SI: 155.9 was similar in both strains and close to that of chloroquine (IC50: 20 nM on the sensitive strain. The antiplasmodial activity was improved with derivatization, thus pointing out the necessity to explore tryptanthrin using medicinal chemistry approaches. Ten (10 of the tested derivatives met the criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 < 100 nM. In addition to their activity on the asexual stages, tryptanthrin and two selected derivatives (NT1 and T8 prevented the maturation of gametocytes at their IC90 concentrations, indicating a transmission-blocking potential. Moreover, NT1 was able to impair gametogenesis by reducing the exflagellation of microgametes by 20% at IC90, while tryptanthrin and T8 had no influence on exflagellation. The results of this study confirm that tryptanthrin and its derivatives are potential antimalarial candidates with abilities to kill the

  1. Synthesis and evaluation of the antiplasmodial activity of tryptanthrin derivatives.

    Onambele, Liliane Abodo; Riepl, Herbert; Fischer, Rainer; Pradel, Gabriele; Prokop, Aram; Aminake, Makoah Nigel

    2015-08-01

    Malaria remains one of the most deadly diseases threatening humankind and is still affecting a significant proportion of the world population, especially in Africa. Chemotherapy is a vital component of the fight against the disease and new antimalarial agents are urgently needed to curb the spread of malaria parasites that are resistant to existing drugs. The natural product tryptanthrin is known for its wide range of activities, including antiplasmodial activity, but its poor solubility has undermined its development as potent antimicrobial and antiprotozoan agent. The aim of this work was to synthesize analogues of tryptanthrin and to evaluate their antiplasmodial activity against the asexual and sexual blood stages of Plasmodium falciparum. Our results suggest that most tryptanthrin analogues retained their antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30-100 nM). The antiplasmodial activity of the most active compound NT1 (IC50: 30 nM; SI: 155.9) was similar in both strains and close to that of chloroquine (IC50: 20 nM) on the sensitive strain. The antiplasmodial activity was improved with derivatization, thus pointing out the necessity to explore tryptanthrin using medicinal chemistry approaches. Ten (10) of the tested derivatives met the criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 < 100 nM. In addition to their activity on the asexual stages, tryptanthrin and two selected derivatives (NT1 and T8) prevented the maturation of gametocytes at their IC90 concentrations, indicating a transmission-blocking potential. Moreover, NT1 was able to impair gametogenesis by reducing the exflagellation of microgametes by 20% at IC90, while tryptanthrin and T8 had no influence on exflagellation. The results of this study confirm that tryptanthrin and its derivatives are potential antimalarial candidates with abilities to kill the intraerythrocytic

  2. Synthesis and Herbicidal Activity of Novel Sulfonylurea Derivatives

    CAO Gang; WANG Mei-yi; WANG Ming-zhong; WANG Su-hua; LI Yong-hong; LI Zheng-ming

    2011-01-01

    Sulfonylurea herbicides have been applied worldwide in agriculture. Some sulfonylurea residues might exist in soil longer than that people expected. However, flupyrsulfuron-methyl-sodium which was firstly reported as a new 5-substituted sulfonylurea herbicide has less than one month residual life. Therefore, 5-substituted benzenesulfonylureas are potential molecules to regulate its residual situation. In order to develop new sulfonylurea derivatives,the substituent on the critical 5-posotion of the benzene ring was optimized. On the basis of our former work on sulfonylureas which contains a characteristic mono-substituted pyrimidine moiety, twenty-six new sulfonylurea derivatives were synthesized and their structures were confirmed by 1H NMR, 31p NMR and elemental analysis. The greenhouse bioassay tests show that some title compounds exhibit potent herbicidal activity.

  3. Synthesis and biological activities of some benzimidazolone derivatives

    B K Karale

    2015-01-01

    Full Text Available The reaction of 5-nitrobenzimidazolone with phenoxyethyl bromide in presence of potassium carbonate in dimethyl formamide obtained 6-nitro-1,3-bis(2-phenoxyethyl-1,3-dihydro-2H-benzimidazol-2-one. It was reduced using stannous chloride to get 6-amino -1,3-bis(2-phenoxyethyl-1, 3-dihydro-2H-benzimidazol -2-one, which was further treated with aromatic sulphonyl chloride to obtain benzimidazolone derivatives, 6a-k. These compounds were tested for antibacterial, antituberculosis and antifungal activity. Most of them have shown very good activity against some gram positive and gram negative microorganisms and fungal strains. Some of them have shown moderate activity against Mycobacterium tuberculosis.

  4. QSAR MODELING OF ANTIBACTERIAL ACTIVITY OF SOME BENZIMIDAZOLE DERIVATIVES

    SANJA O. PODUNAVAC-KUZMANOVIĆ

    2011-03-01

    Full Text Available A quantitative structure-activity relationship (QSAR study has been carried out for a training set of 12 benzimidazole derivatives to correlate and predict the antibacterial activity of studied compounds against Gram-negative bacteria Pseudomonas aeruginosa. Multiple linear regression was used to select the descriptors and to generate the best prediction model that relates the structural features to inhibitory activity. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based on the following descriptors: parameter of lipophilicity (logP and hydration energy (HE. Good agreement between experimental and predicted inhibitory values, obtained in the validation procedure, indicated the good quality of the generated QSAR model.

  5. Design, synthesis and antifungal activity of novel furancarboxamide derivatives.

    Wen, Fang; Jin, Hong; Tao, Ke; Hou, Taiping

    2016-09-14

    Twenty-seven novel furancarboxamide derivatives with a diphenyl ether moiety were synthesized and evaluated for their antifungal activity against Rhizoctonia solani, Botrytis cirerea, Valsa mali and Sphaceloma ampelimum. Antifungal bioassay results indicated that most compounds had good or excellent fungicidal activities for R. solani and S. ampelimum at 20 mg L(-1). Among synthesized compounds, compound 18e showed a greater inhibitory effect against S. ampelimum, with half maximal effective concentration (EC50) values of 0.020 mg L(-1). This strong activity rivals currently used commercial fungicides, such as Boscalid and Carbendazim, and has great potential as a lead compound for future development of novel fungicides. PMID:27191618

  6. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents

    Hao Wang; Shuang-Xi Ren; Ze-Yu He; De-Long Wang; Xiao-Nan Yan; Jun-Tao Feng; Xing Zhang

    2014-01-01

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which l...

  7. SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF NEW PYRAZOLOPYRIDAZINE DERIVATIVES

    Mahfuz Alam

    2015-03-01

    Full Text Available Several new pryrazolo-pyridazine derivatives (4a-h were synthesized through multi-step synthesis and evaluated for their antimicrobial activities. In the first step, 6-phenyl-2,3,4,5-tetrahydropyridazin-3-one (2 was prepared by reacting 4-(4-chlorophenyl-4-oxobutanoic acid (1 with hydrazine hydrate. Then, aryl-aldehydes were reacted with 2 to furnish pyridazinone derivatives (3a-g. Finally, pyridazinones (3a-h were reacted with hydrazine hydrate to furnish the title compounds (4a-h. The newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activities against six microbial strains. Compounds 4d, 4e and 4f exhibited significant antibacterial action, whereas compounds 4c and 4d showed potential antifungal activity. Compound 4d, 5-(4-Chlorophenyl-3-(4-fluorophenyl-3,3a,4,7-tetrahydro-2H-pyrazolo[3,4- ]pyridazine, emerged as lead compound having broad spectrum of antimicrobial action.

  8. Synthesis and biological activities of turkesterone 11?-acyl derivatives

    Laurence Dinan

    2003-02-01

    Full Text Available Turkesterone is a phytoecdysteroid possessing an 11alpha-hydroxyl group. It is an analogue of the insect steroid hormone 20-hydroxyecdysone. Previous ecdysteroid QSAR and molecular modelling studies predicted that the cavity of the ligand-binding domain of the ecdysteroid receptor would possess space in the vicinity of C-11/C-12 of the ecdysteroid. We report the regioselective synthesis of a series of turkesterone 11alpha-acyl derivatives in order to explore this possibility. The structures of the analogues have been unambiguously determined by spectroscopic means (NMR and low-resolution mass spectrometry. Purity was verified by HPLC. Biological activities have been determined in Drosophila melanogaster BII cell-based bioassay for ecdysteroid agonists and in an in vitro radioligand-displacement assay using bacterially expressed D. melanogaster EcR/USP receptor proteins. The 11alpha-acyl derivatives do retain a significant amount of biological activity relative to the parent ecdysteroid. Further, although activity initially drops with the extension of the acyl chain length (C2 to C4, it then increases (C6 to C10, before decreasing again (C14 and C20. The implications of these findings for the interaction of ecdysteroids with the ecdysteroid receptor and potential applications in the generation of affinity-labelled and fluorescently-tagged ecdysteroids are discussed.

  9. Studies on the antioxidant activity of some chromonylrhodanine derivatives.

    Kruk, Irena; Piechowska, Teresa; Berczyński, Paweł; Kładna, Aleksandra; Bozdağ-Dündar, Oya; Ceylan-Unlusoy, Meltem; Aboul-Enein, Hassan Y

    2015-08-01

    Fifteen chromonylrhodamine derivatives (CRs) were synthesized and the antioxidant activity levels were evaluated for the first time. The antioxidant activity potencies of these chromone derivatives were evaluated towards superoxide anion radicals, hydroxyl radicals and 2,2-diphenyl-1-picrylhydrazyl radicals. Also, the total antioxidant capacity of the tested compounds was measured using the ferric-ferrozine assay. The antioxidant activities were investigated using a chemiluminescence (CL) assay, spectrophotometry measurements, direct electron paramagnetic resonance (EPR) and the EPR spin-trapping technique. The 5,5-dimethyl- 1-pyrroline-1-oxide (DMPO) was applied as spin trap. Eleven of the 15 chromone compounds exhibited a decrease in the CL accompanying the superoxide anion radical produced in anhydrous dimethylsulfoxide (DMSO), ranging from 71-94% at concentration of 1 mmol /L; four of these compounds enhanced light emission in the range 231-672%. Similarly, these compounds caused 28-58% inhibition in the intensity of the DMPO-OOH radical EPR signal and the DMPO-OH radical (from 12-48%). Furthermore, three of these compounds showed very good antioxidant response towards the DPPH radical (EC50 : 0.51-0.56 µmol/L) and the high reduction potentials. These findings demonstrate that the chromone compounds tested may be considered as effective free radicals scavengers, a finding that is of great pharmacological importance. PMID:25377006

  10. Antifungal activity of topical microemulsion containing a thiophene derivative

    Geovani Pereira Guimarães

    2014-06-01

    Full Text Available Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05 embedded in a microemulsion (ME. The minimum inhibitory concentration (MIC was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05 showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 µg.mL-1 and good activity against C. neoformans (MIC = 17 µg.mL-1. Candida species were susceptible to ME-5CN05 (70-140 µg.mL-1, but C. neoformans was much more, presenting a MIC value of 2.2 µg.mL-1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.

  11. Synthesis and Antiangiogenic Activity of N-Alkylated Levamisole Derivatives

    Hansen, Anders N.; Bendiksen, Christine D.; Sylvest, Lene;

    2012-01-01

    less effective than antibody treatment and are also associated with serious side effects. The discovery of new chemotypes with efficient antiangiogenic activity is therefore of pertinent interest. (S)-Levamisole hydrochloride, an anthelminthic drug approved for human use and with a known clinical...... normal human dermal fibroblasts. Interestingly, the cluster morphology caused by N-methyllevamisole was different than the clusters observed for levamisole, and a third "cord-like" morphology resembling that of the known drug suramin was observed for an aniline-containing derivative. New chemotypes...

  12. Synthesis and Herbicidal Activity of New Hydrazide and Hydrazonoyl Derivatives

    František Šeršeň

    2015-08-01

    Full Text Available Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and growth of the green algae Chlorella vulgaris. IC50 values of these compounds varied in wide range, from a strong to no inhibitory effect. EPR spectroscopy showed that the active compounds interfered with intermediates Z•/D•, which are localized on the donor side of photosystem II. Fluorescence spectroscopy suggested that the mechanism of inhibitory action of the prepared compounds possibly involves interactions with aromatic amino acids present in photosynthetic proteins.

  13. Antioxidant and cytotoxic activity of mono- and bissalicylic acid derivatives

    Đurendić Evgenija A.

    2014-01-01

    Full Text Available A simple synthesis of mono- and bis-salicylic acid derivatives 1-10 by the transesterification of methyl salicylate (methyl 2-hydroxybenzoate with 3-oxapentane-1,5-diol, 3,6- dioxaoctane-1,8-diol, 3,6,9-trioxaundecane-1,11-diol, propane-1,2-diol or 1-aminopropan- 2-ol in alkaline conditions is reported. All compounds were tested in vitro on three malignant cell lines (MCF-7, MDA-MB-231, PC-3 and one non-tumor cell line (MRC- 5. Strong cytotoxicity against prostate PC-3 cancer cells expressed compounds 3, 4, 6, 9 and 10, all with the IC50 less than 10 μmol/L, which were 11-27 times higher than the cytotoxicity of antitumor drug doxorubicin. All tested compounds were not toxic against the non-tumor MRC-5 cell line. Antioxidant activity of the synthesized derivatives was also evaluated. Compounds 2, 5 and 8 were better OH radical scavengers than commercial antioxidants BHT and BHA. The synthesized compounds showed satisfactory scavenger activity, which was studied by QSAR modeling. A good correlation between the experimental variables IC50 DPPH and IC50 OH and MTI (molecular topological indices molecular descriptors and CAA (accessible Connolly solvent surface area for the new compounds 1, 3, and 5 was observed.

  14. Deriving stellar inclination of slow rotators using stellar activity

    Dumusque, X., E-mail: xdumusque@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2014-12-01

    Stellar inclination is an important parameter for many astrophysical studies. Although different techniques allow us to estimate stellar inclination for fast rotators, it becomes much more difficult when stars are rotating slower than ∼2-2.5 km s{sup –1}. By using the new activity simulation SOAP 2.0 which can reproduce the photometric and spectroscopic variations induced by stellar activity, we are able to fit observations of solar-type stars and derive their inclination. For HD 189733, we estimate the stellar inclination to be i=84{sub −20}{sup +6} deg, which implies a star-planet obliquity of ψ=4{sub −4}{sup +18} considering previous measurements of the spin-orbit angle. For α Cen B, we derive an inclination of i=45{sub −19}{sup +9}, which implies that the rotational spin of the star is not aligned with the orbital spin of the α Cen binary system. In addition, assuming that α Cen Bb is aligned with its host star, no transit would occur. The inclination of α Cen B can be measured using 40 radial-velocity measurements, which is remarkable given that the projected rotational velocity of the star is smaller than 1.15 km s{sup –1}.

  15. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887328

  16. Antimycobacterial Activities of Endolysins Derived From a Mycobacteriophage, BTCU-1

    Meng-Jiun Lai

    2015-10-01

    Full Text Available The high incidence of Mycobacterium infection, notably multidrug-resistant M. tuberculosis infection, has become a significant public health concern worldwide. In this study, we isolate and analyze a mycobacteriophage, BTCU-1, and a foundational study was performed to evaluate the antimycobacterial activity of BTCU-1 and its cloned lytic endolysins. Using Mycobacterium smegmatis as host, a mycobacteriophage, BTCU-1, was isolated from soil in eastern Taiwan. The electron microscopy images revealed that BTCU-1 displayed morphology resembling the Siphoviridae family. In the genome of BTCU-1, two putative lytic genes, BTCU-1_ORF7 and BTCU-1_ORF8 (termed lysA and lysB, respectively, were identified, and further subcloned and expressed in Escherichia coli. When applied exogenously, both LysA and LysB were active against M. smegmatis tested. Scanning electron microscopy revealed that LysA and LysB caused a remarkable modification of the cell shape of M. smegmatis. Intracellular bactericidal activity assay showed that treatment of M. smegmatis—infected RAW 264.7 macrophages with LysA or LysB resulted in a significant reduction in the number of viable intracellular bacilli. These results indicate that the endolysins derived from BTCU-1 have antimycobacterial activity, and suggest that they are good candidates for therapeutic/disinfectant agents to control mycobacterial infections.

  17. Antischistosomal activity of artemisinin derivatives in vivo and in patients.

    Saeed, Mohamed E M; Krishna, Sanjeev; Greten, Henry Johannes; Kremsner, Peter G; Efferth, Thomas

    2016-08-01

    Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms "artemisinin" and "Schistosoma". Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated. PMID:26902577

  18. Nanobionics of Pharmacologically Active Derivatives of Fullerene C60

    The physical-chemical mechanisms of pharmacologic functioning of amino acid derivatives of fullerene C60 (ADF) have been studied. ADF were shown to penetrate through the lipid bilayer of liposomes without destruction of membrane integrity. ADF are able to carry bivalent metal ions through phospholipid bilayer owing to the formation of complexes. It was shown that stereoisomers of ADF selectively penetrate into phospholipid membranes. In contrast to D-isomers, L-isomers penetrate through the phosphatidylcholine membrane into liposome interior. Stereo-specific effect of ADF enantiomers was also observed in reaction of peroxidation of lipids. Besides that, ADF bring about a substantial increase in the catalytic activity of monoaminoxidases A and B. The directed intraprotein electron transfer was studied by creating a donor-acceptor pair in a water solution in the presence of ADF. To realize the intraprotein electron transfer, the model system was produced on the base of apomyoglobin by incorporating ADF (electron acceptor) into the heme pocket of protein instead of removed heme. It was established that the fullerene C60 and its derivatives did not produce specific anti-C60 antibodies, both IgG and IgE classes, while ADF themselves are efficient adjuvants, i.e. they increased the antibody response to poor antigens. Some ADF were found to inhibit the human immunodeficiency virus and human cytomegalovirus infection

  19. Salicin derivatives from Salix glandulosa and their biological activities.

    Kim, Chung Sub; Subedi, Lalita; Park, Kyoung Jin; Kim, Sun Yeou; Choi, Sang Un; Kim, Ki Hyun; Lee, Kang Ro

    2015-10-01

    Two new salicin derivatives, saliglandin (1) and 6'-O-(Z)-p-coumaroylsalicin (2), along with fourteen known analogues (3-16) were isolated from the twigs of Salix glandulosa Seemen. The structures of 1-16 were characterized by the use of NMR methods ((1)H and (13)C NMR, (1)H-(1)H COSY, HSQC and HMBC), chemical hydrolysis, and GC/MS. The full NMR data assignment of the known compounds 6, 13, and 14 are reported for the first time. Isolated compounds were evaluated for their nitric oxide (NO) inhibitory efficacy in lipopolysaccharide (LPS)-activated microglial cell (BV-2). Compounds 2, 5, 8-16 significantly inhibited NO production, compound 11 being the most efficacious (IC50 13.57 μM) respectively. Moreover, compound 16 dramatically increased the nerve growth factor (NGF) production (165.24 ± 11.1%) in C6 glioma cells. Taken together, these results revealed that salicin derivatives from Salix glandulosa might have potent effect as anti-neuroinflammatory agents. PMID:26344424

  20. Synthesis, characterization and antimicrobial activity of some novel benzimidazole derivatives

    Immadisetty Sri Krishnanjaneyulu

    2014-01-01

    Full Text Available A series of novel N-((1H-benzoimidazol-1-yl methyl-4-(1-phenyl-5-substituted-4, 5-dihydro-1-benzoimidazol-1-yl methyl-4-(1-phenyl-5-substituted-4, 5-dihydro-1H-pyrazol-3-yl benzenamine were synthesized by treating various 1-(4-((1H-benzoimidazol-1-yl methylamino phenyl-3-substitutedprop-2-en-1-one with phenyl hydrazine in the presence of sodium acetate through a simple ring closure reaction. The starting material, 1-(4-((1H-benzoimidazol-1-yl methylamino phenyl-3-substitutedprop-2-en-1-one,-benzoimidazol-1-yl methylamino phenyl-3-substitutedprop-2-en-1-one, was synthesized from o-phenylenediamine by a multistep synthesis. All the synthesized compounds were characterized by spectroscopic means and elemental analyses. The title compounds were investigated for in vitro antibacterial and antifungal properties against some human pathogenic microorganisms by employing the agar streak dilution method using Ciprofloxacin and Ketoconazole as standard drugs. All title compounds showed activity against the entire strains of microorganism. Structural activity relationship studies reveal that compounds possessing an electron-withdrawing group display better activity than the compounds containing electron-donating groups, whereas the unsubstituted derivatives display moderate activity. Based on the results obtained, N-((1H-benzoimidazol-1-yl methyl-4-(1-phenyl-5-(4-(trifluoromethyl phenyl-4,5-dihydro-1H-pyrazol-3-yl benzenamine 5i was found to be very active compared with the rest of the compounds and standard drugs that were subjected to antimicrobial assay.

  1. Synthesis and Antiviral Activities of Chiral Thiourea Derivatives

    YAN,Zhikun; CAI,Xuejian; YANG,Xuan; SONG,Baoan; CHEN,Zhuo; BHADURY,S.Pinaki; HU,Deyu; JIN,Linhong; XUE,Wei; LU,Ping

    2009-01-01

    An environmentally benign method has been developed for the synthesis of novel chiral thiourea derivatives in high yields in ionic liquid [Bmim]PF6.The ionic solvent Call be recovered and reused without any loss of its activity.The target compounds were characterized by elemental analysis,IR,1H NMR and 13C NMR spectral data.Accord-ing to the preliminary bioassay,some of the chiral thiourea analogues exhibited moderate in vivo antiviral activities against TMV at a concentration of 500 mg/L.Title chiral compound 3i Was found to possess good in vivo protection,inactivation and curative activities of 57.O%,96.4%and 55.0%,respectively against TMV with an inhibitory concentration at 500 mg/L.The title chiral compound 3i revealed better inactivation effect on TMV(EC50=50.8pg/mL)than Ningnanmycin(EC50=60.2μg/mL).

  2. Optimization of hypocrellin B derivative amphiphilicity and biological activity

    LIU Xin; XIE Jie; ZHANG LuYong; CHEN HongXia; GU Ying; ZHAO JingQuan

    2009-01-01

    To satisfy the dual requirements of the fluent transportation in blood and the affinity to the target tissues of vascular diseases, hypocrellin derivatives with optimized amphiphilicity are expected. In this work, 3-amino-1-propanesulfonic acid and 4-amino-1-butanesulfonic acid substituted hypocrellin B,named compounds 1 and 2, were designed, synthesized in high yields and characterized. Besides greatly strengthened red absorption, the maximum solubility of compound 2 in phosphate buffered saline (PBS) is 4.2 mg/mL which is just enough to prepare an aqueous solution for intravenous injection in clinically acceptable concentration, while the partition coefficient between n-octanol and PBS,5.6, benefits the cell-uptake and biological activity as well. Furthermore, EPR measurements reveal that the photosensitization activities of the two compounds to generate semiquinone anion radicals, superoxide anion radicals and singlet oxygen are a little bit higher than those of taurine substituted hypocrellin B (THB), but the photodynamic activities to human lung cancer A549 cells are several times that of THB, mainly due to increases in lipophilicity and cell-uptake.

  3. Facile synthesis of novel benzotriazole derivatives and their antibacterial activities

    Jun Wan; Peng-Cheng Lv; Na-Na Tian; Hai-Liang Zhu

    2010-07-01

    A series of benzotriazole derivatives (compounds 1-27) were synthesized, and 24 (compounds 1-5, 9-27) of which were first reported. Their chemical structures were confirmed by means of 1H NMR, IR and elemental analyses, coupled with one selected single crystal structure (compound 1). All the compounds were assayed for antibacterial activities against three Gram positive bacterial strains (Bacillus subtilis, Staphylococcus aureus and Streptococcus faecalis) and three Gram negative bacterial strains (Escherichia coli, Pseudomonas aeruginosa and Enterobacter cloacae) by MTT method. Among the compounds tested, most of them exhibited potent antibacterial activity against the six bacterial strains. Most importantly, compound 3-benzotriazol-1-yl-1-(4-bromo-phenyl)-2-[1,2,4]triazol-1-ylpropan-1-one (19) showed the most favourable antibacterial activity against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli and E. cloacae with MIC of 1.56 g/mL, 1.56 g/mL, 1.56 g/mL, 3.12 g/mL, 6.25 g/mL and 6.25 g/mL, respectively.

  4. Solvent-free Synthesis of Thiohydantoin Derivatives with Microwave Activation

    LI Jian-ping; MA Chun-ming; QU Gui-rong

    2004-01-01

    The application of microwave techniques for chemical synthesis has attached considerable interests in recent years because of their enhanced selectivity, reduced reaction time ,easier work-up procedure. The synthesis of thiohydantoin derivatives is useful because they display a wide range of biological activities, including anticonvulsant1, antitumor2, antinociceptive3,thyroxine ingibitory properties4, as well as herbicidal and fungicidal reagents5. Recent studies have shown that some used as synthetic precursor of the marine natural product dispacamide6, and some used to synthesis novel optically active poly(amide-imide)s7. Therefore, many methods of synthesis of thiohydantoins have been explored8~10. Generally, these reactions were carried out in solution and using volatile and poisonous solvent, with long reaction time.In order to overcome the disadvantages discussed above, avoid the use of a solvent and synthesize these valuable compounds rapidly and efficiently, we investigated a new way---solvent-free synthesis using a microwave oven.In this paper, a new and rapid solvent-free synthesis of thiohydantoins with microwave activation was studied. It was found that the addition reaction of aryl isothiocyanates and amino acid in the presence of sodium hydroxide and the cyclizative condensation of adduct in the presence of sodium hydrogen sulphate in a microwave oven takes place quickly.By this new method, twelve thiohydantoins have been synthesized in excellent yield(83~91%).This method has significant advantages such as operational simplicity, shorter reaction time, higher yields and environmental acceptability. The structures of the products were characterized by IR, MS,1H NMR, 13C NMR and elemental analysis. And more detailed work about the application of the thiohydantoins in analytical chemistry and physiological activity is in progress in our laboratory.

  5. Molecular docking assessment of pyridone derivatives as glucokinase activators

    Y. Nanda Kumar

    2012-10-01

    Full Text Available Background: Mutations in glucokinase (GK gene results in maturity onset diabetes of the young 2 (MODY2. It has been observed that GK activators (GKAs can activate GK structure and promote glucose phosphorylation and bring blood glucose levels to normal condition. The present study is aimed to identify the binding mode of pyridone derivatives (PDs as GKAs through molecular docking study. Methods: GK structure was retrieved from the Protein Data Bank (PDB, protonated and energy minimized. A database was constructed with 29 PDs and docked into the allosteric site specified with Y61, R63, S69 and Y215 residues using Molecular Operating Environment (MOE software. Docking conformations were generated using triangle match algorithm and ranked by London dG scoring function. The binding orientations and strength of interactions were evaluated by ligand interaction module of MOE. Results: Molecular docking of 29 PDs in allosteric site of GK gave reliable docking scores, interestingly arene cationic interactions were observed with the compounds PD1, PD12, PD20 and PD21. R63 residue of allosteric site played a predominant role in binding with PDs. Conclusions: PDs can be potentially useful agents in future management strategies of type 2 diabetes mellitus.

  6. Synthesis and antitumor activity of derivatives of 23-hydroxybetulinic acid

    2007-01-01

    A series of natural product 23-hydroxybetulinic acid derivatives were prepared. In the preparation of mono-O-benzoyl ester derivative, it was observed that benzoyl group migrated from 3-O- to 23-O-position during the detritylation.

  7. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity.

    Cortes, Leonel A; Castro, Lorena; Pesce, Bárbara; Maya, Juan D; Ferreira, Jorge; Castro-Castillo, Vicente; Parra, Eduardo; Jara, José A; López-Muñoz, Rodrigo

    2015-01-01

    derivatives of gallic acid are promising trypanocidal agents with mitochondrial activity. PMID:26317199

  8. Antimicrobial activity of nerolidol and its derivatives against airborne microbes and further biological activities.

    Krist, Sabine; Banovac, Daniel; Tabanca, Nurhayat; Wedge, David E; Gochev, Velizar K; Wanner, Jürgen; Schmidt, Erich; Jirovetz, Leopold

    2015-01-01

    Nerolidol and its derivatives, namely cis-nerolidol, O-methyl-nerolidol, O-ethyl-nerolidol, (-)-α-bisabolol, trans,trans-farnesol and its main natural source cabreuva essential oil, were tested for their antimicrobial activity against airborne microbes and antifungal properties against plant pathogens. Among the tested compounds, α-bisabolol was the most effective antimicrobial agent and trans,trans-farnesol showed the best antifungal activity. PMID:25920237

  9. Trypanocidal activity of synthetic heterocyclic derivatives of active quinones from Tabebuia sp.

    Pinto, A V; Pinto, C N; Pinto, M do C; Rita, R S; Pezzella, C A; de Castro, S L

    1997-01-01

    Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho heterocyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents. PMID:9037448

  10. Benzoic acid derivatives from Piper species and their antiparasitic activity.

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2008-09-01

    Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively. PMID:18712933

  11. Synthesis and Anticonvulsant Activity of Some Newer Semicarbazone Derivatives

    Shahnawaz Sameem

    2012-07-01

    Full Text Available A series of 4-(3-Chlorophenyl-1-(substituted acetophenone semicarbazones 3(a-j was synthesized by starting with 3-chloroaniline which on reaction with sodium cyanate yielded 1-(3’-chlorophenyl urea (1 followed by reaction with hydrazine hydrate in the presence of ethanol gave 4-(3’-chlorophenyl semicarbazide (2. Compound (2 on condensation with substituted acetophenone gets converted in to final compounds 3(a-j. The purity of the newer compounds was checked by m.p. and TLC analysis. The structures of the newly synthesized compounds were characterized by FTIR, 1H NMR, EIMS-spectral data and elemental analysis. All the synthesized compounds were evaluated for their anticonvulsant activity by Maximal Electroshock (MES method by using phenytoin as standard at a concentration of 30 mg/kg. The anticonvulsant effect of the newly synthesized compounds was assessed by absence or reduction of hind limb tonic extensor phase. Among the synthesized derivatives compounds 3e and 3j were found to be the most potent compounds in the series.

  12. Optically active vibrational modes of PPV derivatives on textile substrate

    In this work, MEH-PPV and BDMO-PPV films were deposited by spin-coating on “dirty” textile substrates of canvas, nylon, canvas with resin, jeans and on glass and the temperature dependence of the optical properties of them was studied by photoluminescence and Raman (300 K) techniques. The temperature dependence of the energy, of the half line width at half height of the purely electronic peak, of the integrated PL intensity and of the Huang-Rhys factor, S=I(01)/I(00), were obtained directly from the PL spectrum. For an analysis of the vibrational modes involved, Raman measurements were performed on substrates with and without polymers deposited and the results compared with those found in the literature. The films of MEH-PPV and BDMO-PPV showed optical properties similar to those films deposited on other substrates such as glass, metals, etc. It was observed an inversion of the first vibrational band in relation to the purely electronic peak with increasing temperature in the films deposited on nylon and canvas. The vibrational modes obtained by Raman were used to compose the simulation of the PL line shape of BDMO-PPV films on canvas and nylon, using a model proposed by Lin [29]. - Highlights: ► MEH-PPV and BDMO-PPV films were deposited by spin-coating on dirty textile. ► Their properties were studied by photoluminescence and Raman techniques. ► We observed inversion of first vibrational band in relation to purely electronic peak. ► Optically active vibrational modes of PPV derivatives were studied.

  13. Synthesis and Herbicidal Activity of 3-Subsituted Amino-6-(substituted phenoxyl)pyridazine Derivatives

    HU,Fang-Zhong; WANG,Zhan-Ping; LI,Yong-Hong; YANG,Hua-Zheng

    2004-01-01

    @@ In recent years, many pyridazine derivatives have shown highly biological activities, such as fungicides, insecticides and herbicides. Especially, the researches of 3-(substituted phenoxyl)pyridazine derivatives have become the focus of pesticidal chemistry.

  14. Synthesis and SAR Studies of Praziquantel Derivatives with Activity against Schistosoma japonicum

    Chuan-Xin Yu; Bainian Feng; Wen-Hua Fan; Gu-Ping Wang; Xu-Ren Yin; Xia Chen; Li-Jun Song; Wen-Long Wang

    2013-01-01

    The synthesis and structure-activity relationship (SAR) studies of praziquantel derivatives with activity against adult Schistosoma japonicum are described. Several of them showed better worm killing activity than praziquantel and could serve as leads for further optimization.

  15. Photochemistry and photopolymerisation activity of novel thioxanthone derivatives

    In this paper, we aim to examine the influence of a range of 4-oxy substituted groups on the photochemical and photopolymerization of 1-chloro- and 1-phenylthio-thioxanhone. Here we have examined the effect of a number of acyloxy groups attached to the ring 4-position. The study includes a spectroscopic and photoinitiated polymerization evaluation using real time infrared and photocalorimetry. The photoactivities of the initiators are compared with those of the standard industrial system such as the 4-n-propoxy derivative and the basic compound like the 1-chloro-4-hydroxyl derivative which was used to synthesise all the derivatives examined here

  16. Studies on the Synthesis of Derivatives of Marine-Derived Bostrycin and Their Structure-Activity Relationship against Tumor Cells

    Zhigang She

    2012-04-01

    Full Text Available A series of new derivatives (529 of marine-derived bostrycin (1 were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR of bostrycin derivatives was also discussed based on the obtained experimental data.

  17. Acetamide Derivatives with Antioxidant Activity and Potential Anti-Inflammatory Activity

    Giuseppina Tommonaro

    2010-03-01

    Full Text Available This study reports the synthesis and antioxidant activity of some new acetamide derivatives. The compounds’ structures were elucidated by NMR analysis and their melting points were measured. The in vitro antioxidant activity of these compounds was tested by evaluating the amount of scavenged ABTS radical and estimating ROS and NO production in tBOH- or LPS-stimulated J774.A1 macrophages. All compounds were tested for their effect on cell viability by an MTT assay and by a Brine Shrimp Test.

  18. Synthesis and antitumor activity of novel podophyllotoxin derivatives

    Ming Zhao; Min Feng; Shu Fang Bai; Yuan Zhang; Wen Chao Bi; Hong Chen

    2009-01-01

    In order to find compounds with superior bioactivity and overcoming multidrug resistance, a novel series of 4β-N-substituted podophyllotoxin derivatives were synthesized and evaluated as potential antitumor agents. Seven novel podophyllotoxin derivatives were synthesized by linking 4β-amino-4-deoxypodophyllotoxin with alcohols through maleic acid and tested against K562 and K562/A02 using MTT assay in vitro.

  19. Synthesis and Antibacterial Activities of New Metronidazole and Imidazole Derivatives

    Abdul Jabar Kh. Atia

    2009-07-01

    Full Text Available New imidazole ring derivatives comprising 1,3-oxazoline, Schiff's bases, thiadiazole, oxadiazole and 1,2,4-triazole moieties are reported. 3-Aminobiimidazol-4-one compounds 7a-c were synthesized by the reaction of compounds 6a-c with hydrazine hydrate. Biimidazole esters 9a-c were converted into biimidazole hydrazide esters 10a-c. Compounds 7a-c and 10a-c were converted into a variety of derivatives.

  20. Synthesis and DPPH Radical Scavenging Activity of Prenylated Phenol Derivatives

    Héctor Carrasco; Luis Espinoza; Marcela Carvajal; Cesar González; Alejandra Vergara; Lautaro Taborga; Evelyn Baeza; Karen Catalán; Mauricio Osorio; Jacqueline Aravena

    2012-01-01

    The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF3×OEt2. Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho po...

  1. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives.

    Srivastava, Sanjay K; Jha, Amrita; Agarwal, Shiv K; Mukherjee, Rama; Burman, Anand C

    2007-11-01

    The disease of cancer has been ranked second after cardiovascular diseases and plant-derived molecules have played an important role for the treatment of cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Recently, epothilones are being emerging as future potential anti-tumor agents. However, targeted cancer therapy has now been rapidly expanding and small organic molecules are being exploited for this purpose. Amongst target specific small organic molecules, quinazoline was found as one of the most successful chemical class in cancer chemotherapy as three drugs namely Gefitinib, Erlotinib and Canertinib belong to this series. Now, quinazoline related chemical classes such as quinolines and naphthyridines are being exploited in cancer chemotherapy and a number of molecules such as compounds EKB-569 (52), HKI-272 (78) and SNS-595 (127a) are in different phases of clinical trials. This review presents the synthesis of quinolines and naphthyridines derivatives, screened for anticancer activity since year 2000. The synthesis of most potent derivatives in each prototype has been delineated. A brief structure activity relationship for each prototype has also been discussed. It has been observed that aniline group at C-4, aminoacrylamide substituents at C-6, cyano group at C-3 and alkoxy groups at C-7 in the quinoline ring play an important role for optimal activity. While aminopyrrolidine functionality at C-7, 2'-thiazolyl at N-1 and carboxy group at C-3 in 1,8-naphthyridine ring are essential for eliciting the cytotoxicity. This review would help the medicinal chemist to design and synthesize molecules for targeted cancer chemotherapy. PMID:18045063

  2. Design, synthesis and antibacterial activity of new phthalazinedione derivatives

    ABD EL-GALIL M. KHALIL

    2011-03-01

    Full Text Available Dibenzobarallene (1 was utilized as the key intermediate for the synthesis of some new 2-substituted 1,4-dioxo-3,4,4a,5,10,10a-hexahydro-1H-5,10-[1’,2’]-benzenobenzo[g]phthalazine: 2, 5a–d, 8a–c and 10. Condensation of 2 with benzaldehyde or anisaldehyde gave the corresponding acrylonitrile derivatives 3a and b, respectively. Thiophene derivatives 4a and b were obtained via the Gewald reaction of 2 with cyclohexanone or cyclopentanone, respectively. Treatment of 5d with acetyl chloride or p-toluenesulfonyl chloride afforded the corresponding esters 6 and 7, respectively. Cyclization of 8a–c with formalin afforded the corresponding triazine derivatives 9a–c. Ring opening of 10 with sodium hydroxide gave the corresponding triazole derivative 11, which when alkylated with pentyl bromide afforded the pentylthio derivative 12. Representative compounds of the synthesized products were established and evaluated as antibacterial agents.

  3. Activities of new quinoline derivatives against genital pathogens.

    AZNAR;, J.; Caballero, M C; Lozano, M C; Miguel, C. de; Palomares, J C; Perea, E J

    1985-01-01

    The in vitro activities of four quinoline carboxylic acids against 48 strains of Neisseria gonorrhoeae, 10 of Chlamydia trachomatis, and 32 of Ureaplasma urealyticum were compared. Ciprofloxacin was the most active against N. gonorrhoeae and C. trachomatis but had poor bactericidal activity against U. urealyticum, whereas ofloxacin showed the most bactericidal activity against U. urealyticum but was less active than ciprofloxacin against the two former pathogens. Norfloxacin and enoxacin were...

  4. Synthesis and cytotoxic activity of some derivatives of alkyl piperidine.

    Jahan, Sarwat; Akhtar, Shamim; Saify, Zafar Saied; Mushtaq, Nousheen; Sial, Ali Akbar; Kamil, Arfa; Arif, Muhammed

    2013-05-01

    Synthesis of novel phenacyl derivatives of alkyl piperidine as cytotoxic agents via simple and single step reaction procedure is going to be reported here. Twelve new compounds were successfully synthesized in moderate yield and in solid form. Their synthesis was confirmed by TLC, melting point, CHN analysis and through different spectral studies such as UV, IR, Mass and proton NMR. The advantages of this synthetic route are simple operation, mild reaction conditions and good yields. These newly synthesized derivatives were extensively explored for their cytotoxicity by brine shrimp lethality assay. PMID:23625425

  5. The biological activity and the using areas of glycerin derivatives

    The glycerin and its derivatives carry out several important biological functions in alive organism. Glycero lipids related to the neutral lipid groups thanks to presence of polar and hydrophobic groups take part in the developing of structure biogical membranes and in the processes, connected with transfer of matters and ions throw the membranes, energy supply of cell and defense reactions of organism

  6. Free radical-mediated activation of hydrazine derivatives.

    Kalyanaraman, B.; Sinha, B. K.

    1985-01-01

    Hydrazines are known to undergo oxidative activation in several enzymatic systems in vitro. Free radicals or carbonium ions have been proposed as active intermediates during such activation. The toxic effects elicited by hydrazines have also been linked to free radical-mediated activation. In this report, we have reviewed the identification of organic free radicals from hydrazines by direct ESR and ESR-spin trapping.

  7. Synthesis, cytotoxicity, and hemolytic activity of 6'-O-substituted dioscin derivatives.

    Li, Wei; Qiu, Zaozao; Wang, Yibing; Zhang, Yichun; Li, Ming; Yu, Jia; Zhang, Lihong; Zhu, Ziyan; Yu, Biao

    2007-12-28

    Dioscin derivatives (1-12) with a variety of substitutions at the 6'-OH of the chacotriosyl residue and the 3',6'-anhydrosaponin derivatives (26, 30, and 32) were synthesized. All these derivatives showed much lower cytotoxicity than that of the parent dioscin, while their hemolytic activities were partially retained depending on the various 6'-O-substitutions. PMID:17945208

  8. Microwave Assisted Synthesis of Some New Heterocyclic Spiro-Derivatives with Potential Antimicrobial and Antioxidant Activity

    Mohamed Mohamed Youssef

    2010-12-01

    Full Text Available Homophthalic anhydride reacts with different aromatic amines to produce N-substituted homophthalimides. Bromination of the latter produces 4,4-dibromo-homophthalimide derivatives that can be used as precursors for spiro-derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiro-isoquinoline derivatives. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro-derivatives. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, 1H-NMR and 13C-NMR. The newly synthesized compounds were tested for their antimicrobial and antioxidant activities, showing weak or no antimicrobial activity. On the other hand select compounds showed promising antioxidant activities.

  9. Cytotoxic Activity of Some Novel Dicoumarin Derivatives in vitro

    ZHANG Hui; YU Tian-zhi; ZHAO Yu-ling; FAN Duo-wang; DING Lan; ZHANG Shi-dong

    2009-01-01

    Some novel dicoumarin derivatives, triethylene-glycol dibenzo[5,6] coumarin-3-carboxylate(1a). PEG (600) dibenzo[5,6]coumarin-3-carboxylate(1b), triethylene-glycol di[7-(N,N'-diethylamino)]-coumarin-3-carboxy-late(2a), were synthesized. The cytotoxic effect of these compounds, along with benzo[5,6]coumarin-3-carboxylic acid(1) and 7-(N,N'-diethylamino)-coumarin-3-carboxylic acid(2), against the SGC-7901 cell lines were determined by Sulforhodamine B(SRB) assay. The preliminary cytotoxicity screening process revealed that the investigated dicoumarin derivatives induced 50% inhibition of the cell viability of SGC-7901 cells at micromolar concentrations. Compound 2a was proved superior to compound la according to the IC_(50) values obtained and the agent with PEG moiety has more contribution to cell-killing ability of the molecules than the remaining agents.

  10. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity

    Cortes, Leonel A.; Lorena Castro; Bárbara Pesce; Maya, Juan D.; Jorge Ferreira; Vicente Castro-Castillo; Eduardo Parra; José A Jara; Rodrigo López-Muñoz

    2015-01-01

    disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a gallate g...

  11. Cytotoxicity and Antineoplastic Activities of Alkylamines and Their Borane Derivatives

    Hall, Iris H.; Tse, Elaine Y.; Muhammad, Rosallah A.

    1996-01-01

    The alkylamines and their related boron derivatives demonstrated potent cytotoxicity against the growth of murine and human tissue cultured cells. These agents did not necessarily require the boron atom to possess potent cytotoxic action in certain tumor lines. Their ability to suppress tumor cell growth was based on their inhibition of DNA and protein syntheses. DNA synthesis was reduced because purine synthesis was blocked at the enzyme site of IMP dehydrogenase by the agents. In addition r...

  12. Novel Gallate Triphenylphosphonium Derivatives with Potent Antichagasic Activity

    Cortes, Leonel A.; Castro, Lorena; Pesce, Bárbara; Maya, Juan D.; Ferreira, Jorge; Castro-Castillo, Vicente; Parra, Eduardo; José A. JARA; López-Muñoz, Rodrigo

    2015-01-01

    Chagas disease is one of the most neglected tropical diseases in the world, affecting nearly 15 million people, primarily in Latin America. Only two drugs are used for the treatment of this disease, nifurtimox and benznidazole. These drugs have limited efficacy and frequently induce adverse effects, limiting their usefulness. Consequently, new drugs must be found. In this study, we demonstrated the in vitro trypanocidal effects of a series of four gallic acid derivatives characterized by a ga...

  13. Quantitative relationships between structure and cytotoxic activity of flavonoid derivatives. An application of Hirshfeld surface derived descriptors.

    Kupcewicz, Bogumiła; Małecka, Magdalena; Zapadka, Mariusz; Krajewska, Urszula; Rozalski, Marek; Budzisz, Elzbieta

    2016-07-15

    Quantitative relationships between the structure and cytotoxic activity of series flavonoid derivatives were examined. The first regression-based model, developed for 18 flavanone-2-pyrazoline hybrids, involved two interpretable descriptors: a Mor04v and partial atomic charge. The second model, developed for structurally diverse set of compounds, was based on descriptors derived from Hirshfeld surface analysis. This model suggests that cytotoxic activity of compounds can be successfully predicted based on a fraction of H⋯H contacts and a fraction of interactions involving a halogen atom. For non-halogen derivatives, the data reveal that cytotoxic activity is inversely proportional to the percentage of O⋯H and N⋯H close contacts to Hirshfeld surface, while directly proportional to the percentage of H⋯H interactions. Chlorine (1k) and bromine (1l) derivatives of compounds, containing flavanone fused with N-methyl-2-pyrazoline, exhibited high cytotoxic potential against HL-60 cancer cell line (IC50<10μM). The cytotoxicity of 1k and 1l towards normal cells (HUVEC) was 10 and 25-fold lower, respectively. PMID:27234147

  14. Synthesis and Fungicidal Activity of β-Carboline Alkaloids and Their Derivatives

    Zhibin Li

    2015-07-01

    Full Text Available A series of β-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35% than commercial antiviral agent validamycin (36.4%; compound F16 exhibited high fungicidal activity against Oospora citriaurantii ex Persoon (43.28%. Some of the alkaloids and their derivatives (compounds F4 and F25 exhibited broad-spectrum fungicidal activity. Specifically, compound F4 exhibited excellent high broad-spectrum fungicidal activity in vitro, and the curative and protection activities against P. litchi in vivo reached 92.59% and 59.26%, respectively. The new derivative, F4, with optimized physicochemical properties, obviously exhibited higher activities both in vitro and in vivo; therefore, F4 may be used as a new lead structure for the development of fungicidal drugs.

  15. Design, synthesis and antifungal activity of novel triazole derivatives

    Qing lie Zhao; Yan Song; Hong Gang Hu; Shi Chong Yu; Qiu Ye Wu

    2007-01-01

    Twenty-three 1 -(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N-cycloproyl-N-substituted-amino)-2-propanols were designed and synthesized on the basis of the active site of lanosterol 14α-demethylase.In vitro antifungal activities showed that some of the title compounds had higher antifungal activity and broader antifungal spectrum than fluconazole.

  16. Structure–anticancer activity relationships among 4-azolidinone-3-carboxylic acids derivatives

    Lesyk R. B.; Kaminskyy D. V.

    2010-01-01

    The aim of present research was investigation of anticancer activity of 4-azolidinone-3-carboxylic acids derivatives, and studies of structure–activity relationships (SAR) aspects. Methods. Organic synthesis; spectral methods; anticancer screening was performed according to the US NCI protocol (Developmental Therapeutic Program). Results. The data of new 4-thiazolidinone-3-alkanecarboxylic acids derivatives in vitro anticancer activity were described. The most active compounds which belong to...

  17. Synthesis of some N-[4-(benzothiazole-2yl) phenyl]-2-aryloxyacetamide derivatives and their anticancer activities.

    Tay, Funda; Yurttaş, Leyla; Demirayak, Seref

    2012-08-01

    In this study, some N-[4-(Benzothiazole-2-yl) phenyl]-2-aryloxyacetamide derivatives were prepared by reacting N-[4-(benzothiazole-2yl)phenyl]-2-chloroacetamide and different substituent phenol or thiophenol derivatives. The anticancer activities of the compounds obtained were investigated. It was observed that some of the compounds, namely 25 and 38, showed notable anticancer activity. PMID:21823837

  18. N4-amino-acid derivatives of 6-azacytidine: structure-activity relationship.

    Alexeeva, I; Palchikovskaya, L; Shalamay, A; Nosach, L; Zhovnovataya, V; Povnitsa, O; Dyachenko, N

    2000-01-01

    Several N4-derivatives of 6-azacytidine were synthesized using of Vorbrüggen's condensation method. Their antiviral activity with respect to the adenovirus serotypes 2 and 5 in Hep-2 cells culture was studied and primary specific activity was determined. Correlation between chemical structure of new 6-azacytidine derivatives and their biological properties is discussed. PMID:10961682

  19. Antioxidant and cytotoxic activity of mono- and bissalicylic acid derivatives

    Đurendić Evgenija A.; Savić Marina P.; Jovanović-Šanta Suzana S.; Sakač Marija N.; Kojić Vesna V.; Szécsi Mihály; Oklješa Aleksandar M.; Poša Mihalj M.; Penov-Gaši Katarina M.

    2014-01-01

    A simple synthesis of mono- and bis-salicylic acid derivatives 1-10 by the transesterification of methyl salicylate (methyl 2-hydroxybenzoate) with 3-oxapentane-1,5-diol, 3,6- dioxaoctane-1,8-diol, 3,6,9-trioxaundecane-1,11-diol, propane-1,2-diol or 1-aminopropan- 2-ol in alkaline conditions is reported. All compounds were tested in vitro on three malignant cell lines (MCF-7, MDA-MB-231, PC-3) and one non-tumor cell line (MRC- 5). Strong cytotoxicity agains...

  20. Porous texture evolution in Nomex-derived activated carbon fibers.

    Villar-Rodil, S; Denoyel, R; Rouquerol, J; Martínez-Alonso, A; Tascón, J M D

    2002-08-01

    In the present work, the textural evolution of a series of activated carbon fibers with increasing burn-off degree, prepared by the pyrolysis and steam activation of Nomex aramid fibers, is followed by measurements of physical adsorption of N(2) (77 K) and CO(2) (273 K) and immersion calorimetry into different liquids (dichloromethane, benzene, cyclohexane). The immersion calorimetry results are discussed in depth, paying special attention to the choice of the reference material. The activated carbon fibers studied possess an essentially homogeneous microporous texture, which suggests that these materials may be applied in gas separation, either directly or with additional CVD treatment. PMID:16290775

  1. Synthesis and antitubercular activity of isoniazid condensed with carbohydrate derivatives

    Sílvia H. Cardoso

    2009-01-01

    Full Text Available A series of 13 compounds analogous of isoniazid condensed with carbohydrate was synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC90 in μg/mL. Several compounds exhibited antitubercular activity (0.31-3.12 μg/mL when compared with first line drugs such as isoniazid (INH and rifampicin (RIP and could be a good starting point to develop new compounds against tuberculosis.

  2. Structure, toxicity and antibiotic activity of gramicidin S and derivatives.

    Swierstra, J; Kapoerchan, V; Knijnenburg, A; van Belkum, A; Overhand, M

    2016-05-01

    Development of new antibiotics is declining whereas antibiotic resistance is rising, heralding a post-antibiotic era. Antimicrobial peptides such as gramicidin S (GS), exclusively topically used due to its hemolytic side-effect, could still be interesting as therapeutic compounds. By modifying the amino-acid composition of GS, we synthesized GS analogues. We now show that derivative VK7 has a lower MIC (7.8-31.2 μg/ml, median 15.6 μg/ml) against strains of multi-drug resistant (MDR) Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa than GS has (3.9-62.5 μg/ml, median 31.3 μg/ml). Low MICs for both VK7 and GS were observed for Staphylococcus aureus and Enterococcus faecium. VK7 showed reduced haemolysis and less lactate dehydrogenase release. All compounds were fully bactericidal at MIC values. Modification of GS enables production of novel derivatives potentially useful for systemic treatment of human infections. PMID:26886453

  3. Synthesis and Evaluation of Antioxidant Activity of Semicarbazone Derivatives

    Manmohan Singhal

    2011-04-01

    Full Text Available In present study, a series of chalconesemicarbazones was synthesized and evaluated for antioxidant activity by DPPH free radical scavenging assay. Most of the compounds were found to be potent antioxidant. Free radicals play an important role in various pathological and xenotoxic effects so antioxidant may have protective role in these pathological conditions. Based on the results of an anti-oxidant study, Compound 23 was the most active compound. The highest scavenger activity observed in compound 23 is probably due to the presence of hydroxyl group in the acetophenic moiety and methoxy group in aldehydic moiety of chalcone. It was found that methoxy and hydroxyl substituted chalconesemicarbazones were potent nitric oxide scavenger and unsubstituted compound showed very less activity.

  4. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

    Stavrakov, Georgi; Valcheva, Violeta; Voynikov, Yulian; Philipova, Irena; Atanasova, Mariyana; Konstantinov, Spiro; Peikov, Plamen; Doytchinova, Irini

    2016-03-01

    The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non-toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. PMID:26502828

  5. QSAR analysis on Spodoptera litura antifeedant activities for flavone derivatives

    Duchowicz, Pablo R., E-mail: pabloducho@gmail.com [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, 1900 La Plata (Argentina); Goodarzi, Mohammad [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, 1900 La Plata (Argentina); Ocsachoque, Marco A. [Centro de Investigacion y Desarrollo en Ciencias Aplicadas ' Dr. J. J. Ronco' (CINDECA), Departamento de Quimica, Facultad de Ciencias Exactas, UNLP-CONICET. Calle 47 No 257, B1900AJK La Plata (Argentina); Romanelli, Gustavo P. [Centro de Investigacion y Desarrollo en Ciencias Aplicadas ' Dr. J. J. Ronco' (CINDECA), Departamento de Quimica, Facultad de Ciencias Exactas, UNLP-CONICET. Calle 47 No 257, B1900AJK La Plata (Argentina); Catedra de Quimica Organica, Facultad de Ciencias Agrarias y Forestales, UNLP. Calles 60 y 119, B1904AAN La Plata (Argentina); Ortiz, Erlinda del V. [Facultad de Tecnologia y Ciencias Aplicadas, Universidad Nacional de Catamarca, Av. Maximio Victoria 55, (4700), Catamarca (Argentina); Autino, Juan C.; Bennardi, Daniel O.; Ruiz, Diego M. [Catedra de Quimica Organica, Facultad de Ciencias Agrarias y Forestales, UNLP. Calles 60 y 119, B1904AAN La Plata (Argentina); Castro, Eduardo A. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas INIFTA (UNLP, CCT La Plata-CONICET), Diag. 113 y 64, Sucursal 4, C.C. 16, 1900 La Plata (Argentina)

    2009-12-20

    We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED{sub 50} feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure-Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds. After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure-activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-({alpha}-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED{sub 50} = 1.162.

  6. Synthesis and Antimicrobial Activity of 1,2-Benzothiazine Derivatives.

    Patel, Chandani; Bassin, Jatinder P; Scott, Mark; Flye, Jenna; Hunter, Ann P; Martin, Lee; Goyal, Madhu

    2016-01-01

    A number of 1,2-benzothiazines have been synthesized in a three-step process. Nine chalcones 1-9 bearing methyl, fluoro, chloro and bromo substituents were chlorosulfonated with chlorosulfonic acid to generate the chalcone sulfonyl chlorides 10-18. These were converted to the dibromo compounds 19-27 through reaction with bromine in glacial acetic acid. Compounds 19-27 were reacted with ammonia, methylamine, ethylamine, aniline and benzylamine to generate a library of 45 1,2-benzothiazines 28-72. Compounds 28-72 were evaluated for their antimicrobial activity using broth microdilution techniques against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Proteus vulgaris and Salmonella typhimurium). The results demonstrated that none of the compounds showed any activity against Gram-negative bacteria P. vulgaris and S. typhimurium; however, compounds 31, 33, 38, 43, 45, 50, 53, 55, 58, 60, 63 and 68 showed activity against Gram-positive bacteria Bacillus subtilis and Staphylococcous aureus. The range of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was 25-600 µg/mL, though some of the MIC and MBC concentrations were high, indicating weak activity. Structure activity relationship studies revealed that the compounds with a hydrogen atom or an ethyl group on the nitrogen of the thiazine ring exerted antibacterial activity against Gram-positive bacteria. The results also showed that the compounds where the benzene ring of the benzoyl moiety contained a methyl group or a chlorine or bromine atom in the para position showed higher antimicrobial activity. Similar influences were identified where either a bromine or chlorine atom was in the meta position. PMID:27376253

  7. QSAR analysis on Spodoptera litura antifeedant activities for flavone derivatives

    We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED50 feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure-Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds. After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure-activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-(α-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED50 = 1.162.

  8. Antioxidant activity of N-acetyl-glucosamine based thiazolidine derivative

    Li Chunlei; Yang Yan; Han Baoqin; Liu Wanshun

    2007-01-01

    N-acetyl-glucosamine,the monomer of chitin,was cyclo-condensed with L-cysteine to prepare thiazolidine derivative:2-N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid(GlcNAcCys).The stability of GlcNAcCys was evaluated by high performance liquid chromatography(HPLC)measurement.The results showed that GlcNAcCys Was more stable than other TCA derivatives,especially in alkaline condition.The direct in vitro antioxidative properties of GlcNAcCys were investigated by using UV radiation-induced lipid peroxidation(LPO)in mitochondria and nuclei and.OH-induced LPO in red blood cell (RBC)ghosts models.UV radiation caused dose-dependent LPO in both mitochondria and nuclei,this effect Was catalvzed by addition of Fd2+ while prevented by co-incubation with GlcNAcCys.When nuclei and mitochondria Was treated with 100μl,300μl,500μl of GlcNAcCys and co-incubated at 37℃ for 30min,LPO was decreased to 96%,72%,68%in nuclei and 95%,72%,68% in mitochondria when compared to the UV radiation group respectively.Hydroxyl radicals(.OH)generated by Fenton reaction induced LPO in RBC ghosts.Pretreatment of RBC ghosts with GlcNAcCys could induce antioxidant RBC ghosts and inhibit concentration-dependent malondialdehyde(MDA)formation in antioxidant RBC ghosts.Its inhibition percent Was 14%,35%,36%,42%at 10,20,30,40ms/ml respectively.In a conclusion,the data suggest that GlcNAcCys has antioxidant ability and can significantly inhibit lipid peroxidation in biological samples tested in vitro.

  9. Antituberculosis: Synthesis and Antimycobacterial Activity of Novel Benzimidazole Derivatives

    Yeong Keng Yoon

    2013-01-01

    Full Text Available A total of seven novel benzimidazoles were synthesized by a 4-step reaction starting from 4-fluoro-3-nitrobenzoic acid under relatively mild reaction conditions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv (MTB-H37Rv and INH-resistant M. tuberculosis (INHR-MTB strains using agar dilution method. Three of them displayed good activity with MIC of less than 0.2 μM. Compound ethyl 1-(2-(4-(4-(ethoxycarbonyl-2-aminophenylpiperazin-1-ylethyl-2-(4-(5-(4-fluorophenylpyridin-3-ylphenyl-1H-benzo[d]imidazole-5-carboxylate (5g was found to be the most active with MIC of 0.112 μM against MTB-H37Rv and 6.12 μM against INHR-MTB, respectively.

  10. Synthesis, Characterization and antimicrobial activity of Cyanopyridine derivatives with Vanillin.

    K. N. Borkhataria

    2014-02-01

    Full Text Available Cyanopyridines play a vital role owing to their range of biological and physiological activities. In the light of these biological activities and variety of industrial applications, some new of 6-Aryl-4-[4’-(p-chlorobenzyloxy-3’-methoxyphenyl]-2-methoxy-3-cyanopyridines (1a-l & 6-Aryl-4-[4’-(p-chlorobenzyloxy-3’-methoxyphenyl]-2-ethoxy-3-cyanopyridine (2a-l have been prepared, by the cyclocondensation of 1-Aryl-3-[4’-(p-chlorobenzyloxy-3’-methoxyphenyl]-propenones type (I with malononitrile in presence of Sodiummethoxide & Sodiumethoxide. All the prepared compounds were characterized by their spectral (I.R., N.M.R. ,Mass data and screened for their antimicrobial activities.

  11. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    WANG Jing; ZHANG Quanbin; ZHANG Zhongshan; HOU Yun; ZHANG Hong

    2011-01-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminariajaponica,an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT).The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content,sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  12. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

  13. Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

    Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

    2013-07-01

    A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. PMID:23673223

  14. Synthesis, Characterization and Antimicrobial Activity of Azol Substituted Derivatives

    Barve Ashutosh

    2009-10-01

    Full Text Available A series of dichlorides (Ia-h followed by 1, 3, 4-Thiadiazol-2-Amine (II a-h were synthesized by using various dicarboxylic acids(a-h, the further reaction of (I was carried out with thiosemicarbazide in presence of sulphuric acid to converted into corresponding 1, 3, 4-Thiadiazol-2-Amine (II a-h The structures of these compounds were confirmed by IR, NMR and Mass spectral analysis. The newly synthesized compounds were evaluated for the antibacterial and antifungal activity. The results show that compound (IIa, (IIe, (IIf and (IIh exhibited moderate to good antibacterial and antifungal activity at 5-100 mcg/ml.

  15. Antibacterial Characteristics and Activity of Water-Soluble Chitosan Derivatives Prepared by the Maillard Reaction

    Ying-Chien Chung

    2011-10-01

    Full Text Available The antibacterial activity of water-soluble chitosan derivatives prepared by Maillard reactions against Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Escherichia coli, Shigella dysenteriae, and Salmonella typhimurium was examined. Relatively high antibacterial activity against various microorganisms was noted for the chitosan-glucosamine derivative as compared to the acid-soluble chitosan. In addition, it was found that the susceptibility of the test organisms to the water-soluble chitosan derivative was higher in deionized water than in saline solution. Metal ions were also found to reduce the antibacterial activity of the water-soluble chitosan derivative on S. aureus. The marked increase in glucose level, protein content and lactate dehydrogenase (LDH activity was observed in the cell supernatant of S. aureus exposed to the water-soluble chitosan derivative in deionized water. The results suggest that the water-soluble chitosan produced by Maillard reaction may be a promising commercial substitute for acid-soluble chitosan.

  16. Superior capacitive performance of active carbons derived from Enteromorpha prolifera

    Highlights: • An ocean biomass, Entromorphra prolifera, has been processed into supercapacitor electrodes. • KOH activation can prepare hierarchical porous carbon. • The as-prepared carbons have high capacitance with good rate capability. • This work provided an approach to value-added products from an ocean biomass. - Abstract: Enteromorpha prolifera (E.prolifera), an ocean biomass, was used as raw materials to prepare active carbons by a two-step strategy (pre-carbonization followed by chemical activation). The as-prepared active carbons have been characterized by a variety of means such as N2 adsorption, field emission scanning electron microscope, transmission electron microscope, Raman spectroscopy. The results showed that the carbons have large surface area and developed porosity with micro-meso hierarchical pore texture. As evidenced by electrochemical measurements, the specific capacitance of the carbons can reach up to 296 F g−1. More importantly, the carbons can maintain a high capacitance of up to 152 F g−1 at a very high current density of 30 A g−1, highlighting the promise of the carbons for high power applications

  17. Synthesis and antitumor activity of some substituted indazole derivatives.

    Abbassi, Najat; Rakib, El Mostapha; Chicha, Hakima; Bouissane, Latifa; Hannioui, Abdellah; Aiello, Cinzia; Gangemi, Rosaria; Castagnola, Patrizio; Rosano, Camillo; Viale, Maurizio

    2014-06-01

    Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl]arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose-dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds. PMID:24554280

  18. Antiplatelet Activities of Newly Synthesized Derivatives of Piperlongumine

    Piperlongumine, a pyridine alkaloid isolated from Piper longum L., exhibited a potential inhibitory effect on washed rabbit platelet aggregation induced by collagen, arachidonic acid (AA) and platelet activating factor (PAF), without affecting that induced by thrombin. Piperlongumine was used as a ...

  19. Synthesis and Antimicrobial Activities of Some Pyrazoline Derivatives

    Ganguly Sushmita S

    2012-10-01

    Full Text Available An efficient synthesis of 3, 5-disubstituted-2-pyrazoline was carried out by the condensation of chalcones with hydrazine hydrate in ethanol in presence of piperidine. The newly synthesized compounds were characterized by 1H NMR spectroscopy, IR spectroscopy, MS, elemental analysis and screened for their antimicrobial activity against various strains of bacteria and fungi.

  20. Thermodynamic Derivation of the Activation Energy for Ice Nucleation

    Barahona, D.

    2015-01-01

    Cirrus clouds play a key role in the radiative and hydrological balance of the upper troposphere. Their correct representation in atmospheric models requires an understanding of the microscopic processes leading to ice nucleation. A key parameter in the theoretical description of ice nucleation is the activation energy, which controls the flux of water molecules from the bulk of the liquid to the solid during the early stages of ice formation. In most studies it is estimated by direct association with the bulk properties of water, typically viscosity and self-diffusivity. As the environment in the ice-liquid interface may differ from that of the bulk, this approach may introduce bias in calculated nucleation rates. In this work a theoretical model is proposed to describe the transfer of water molecules across the ice-liquid interface. Within this framework the activation energy naturally emerges from the combination of the energy required to break hydrogen bonds in the liquid, i.e., the bulk diffusion process, and the work dissipated from the molecular rearrangement of water molecules within the ice-liquid interface. The new expression is introduced into a generalized form of classical nucleation theory. Even though no nucleation rate measurements are used to fit any of the parameters of the theory the predicted nucleation rate is in good agreement with experimental results, even at temperature as low as 190 K, where it tends to be underestimated by most models. It is shown that the activation energy has a strong dependency on temperature and a weak dependency on water activity. Such dependencies are masked by thermodynamic effects at temperatures typical of homogeneous freezing of cloud droplets; however, they may affect the formation of ice in haze aerosol particles. The new model provides an independent estimation of the activation energy and the homogeneous ice nucleation rate, and it may help to improve the interpretation of experimental results and the

  1. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster.

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  2. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    Nieves Baenas

    2016-02-01

    Full Text Available We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo, a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.

  3. Synthesis, antimicrobial activity of lamotrigine and its ammonium derivatives

    Yong Qian; Peng-Cheng Lv; Lei Shi; Rui-Qin Fang; Zhong-Cheng Song; Hai-Liang Zhu

    2009-07-01

    Antiepileptic drug lamotrigine and its thirteen ammonium salt complexes (4a-4m) were synthesized and characterized by IR, elemental analysis, 1H-NMR, and MS spectral methods. Many of the ammonium salts (4a-4m) were first reported. Furthermore, the crystal structure of compound 3 was determined by single crystal X-ray diffraction analysis. All these complexes were tested in vitro for their antibacterial activity (Bacillus subtilis, Staphylococcus aureus, Enterococus faecalis, Escherichia coli, Pseudomonas aeruginosa and Enterobacter cloacae). The results indicated that most of the complexes showed good antibacterial activity against Gram-positive (B. subtilis, S. aureus and S. faecalis), but showed mild, even inactive against Gram-negative bacterial strains.

  4. Novel macromolecules derived from coumarin: synthesis and antioxidant activity

    Al-Amiery, Ahmed A.; Al-Majedy, Yasameen K.; Kadhum, Abdul Amir H.; Mohamad, Abu Bakar

    2015-07-01

    The rational design of 4-hydroxycoumarins with tailor-made antioxidant activities is required nowadays due to the wide variety of pharmacologically significant, structurally interesting of coumarins and researcher orientation toward green chemistry and natural products. A simple and unique coumarins have been achieved by reaction of 4-hydroxycoumarin with aromatic aldehyde accompanied with the creation of a macromolecules have 2-aminothiazolidin-4-one. The molecular structures of the compounds were characterized by the Fourier transformation infrared and Nuclear magnetic resonance spectroscopies, in addition to CHN analysis. The scavenging abilities of new compounds against stable DPPH radical (DPPH•) and hydrogen peroxide were done and the results show that the compounds exhibited high antioxidant activates.

  5. Antibacterial Activity of Melittin Derived from Honey Bee Venom

    Mohsen Momenzadeh; Delavar Shahbazzadeh1; Mohammad Dakhili; Mohammad Reza Zolfaghari; Kamran Pooshang Bagheri

    2014-01-01

    Abstract Background and objective: Bacterial peritonitis is one of the nosocomial infections that is due to direct invasion of bacteria to peritoneal membrane. Resistance to antibiotic is of great significance in this disease and could be led to morbidity and mortality of patients. During the past decade, tracing for natural antimicrobial peptide is more considered. Among them, melittin has been extracted from honey bee venom and its antibacterial activity is being examined. The main goal...

  6. Radioprotector and antineoplastic activity of certain tetrazole derivatives

    For a modification of the biological activity of the 5-substituted tetrazoles that were studied earlier, the authors synthesized products of their alkylation by Mannich bases from phenols, since substances with good radioprotective properties have been detected among the phenols. The acute toxicity was determined on mice and treatment of the data on toxicity of the compounds studied was performed according to the method of Litchfield and Wilcoson, and LD16, LD50, and LD84 were determined

  7. Immunomodulatory and anti-inflammatory activity of selected osthole derivatives.

    Zimecki, Michał; Artym, Jolanta; Cisowski, Wojciech; Mazol, Irena; Włodarczyk, Maciej; Gleńsk, Michał

    2009-01-01

    From osthole [7-methoxy-8-(3-methyl-but-2-enyl)-chromen-2-one] (I), obtained by selective extraction of Peucedanum ostruthium (L.) W. Koch roots, ostholic acid (II) was synthetized as a result of its oxidation with chromium trioxide. From ostholic acid, through its chloride, four amides were obtained: the morpholide 1, the p-chloro-benzylamide 2, the piperidine 3 and the N-methyl-piperazide 4. Except for 1, other compounds have not been described before. The amides 1-4 and their precursor osthole (I) were tested for their potential activities in selected immunological assays. The compounds showed moderate inhibitory activity in the humoral immune response to sheep erythrocytes in mice in vitro, and 4 was the most suppressive. The effects of 1 and 3 on concanavalin A- and pokeweed mitogen-induced mouse splenocyte proliferation were inhibitory and those of 4 stimulatory. The compounds were also tested for their activity on tumour necrosis factor a and interleukin 6 production, induced by lipopolysaccharide, in cultures of rat peritoneal cells and human peripheral blood mononuclear cells. Compounds 1, 3 and 4 inhibited tumour necrosis factor a (rat cells), whereas compound 2 stimulated the production of both cytokines. Compounds 1, 2 and 3 were also strongly inhibitory on tumour necrosis factor a production in human blood cells (73, 78 and 80% inhibition at 10 microg/ml, respectively). On the other hand, 2 and 4 stimulated the interleukin 6 production (2- to 3-fold stimulation). In addition, 2 and 4 suppressed the carrageenan-induced inflammation in mice (56.5% and 68.3% inhibition, respectively). In summary, the compounds predominantly displayed suppressive and antiinflammatory activities in the investigated models. PMID:19678539

  8. Synthesis and Antimicrobial Activity of Some Chalcone Derivatives

    Prasad, Y. Rajendra; Rao, A. Lakshmana; Rambabu, R.

    2008-01-01

    In an effort to develop antimicrobial agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehydes in the presence of aqueous solution of potassium hydroxide and ethanol at room temperature. The synthesized compounds were characterized by means of their IR, 1H-NMR spectral data and elemental analysis. All the compounds were tested for their antibacterial and antifungal activities by the cup plate method.

  9. Antibacterial Activity of Melittin Derived from Honey Bee Venom

    Mohsen Momenzadeh

    2014-01-01

    Full Text Available Abstract Background and objective: Bacterial peritonitis is one of the nosocomial infections that is due to direct invasion of bacteria to peritoneal membrane. Resistance to antibiotic is of great significance in this disease and could be led to morbidity and mortality of patients. During the past decade, tracing for natural antimicrobial peptide is more considered. Among them, melittin has been extracted from honey bee venom and its antibacterial activity is being examined. The main goal of this study was isolation of melittin from honey bee venom and evaluation of its antibacterial activity against the agents of bacterial peritonitis. Materials and methods: Honey bee venom prepared using electrical stimulation and the quality of venom confirmed by SDS-PAGE. Melittin isolated from the venom using a linear gradient of acetonitrile and C18 column by Reverse Phase-High Performance Chromatography (RP-HPLC. Minimal Inhibition and Bactericidal concentration for melittin examined on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Results: Honey bee venom composed of twenty distinct fraction in which melittin was the major one. Melittin inhibited Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa growth at 0.39, 6.25, and 12.5 µg and was bactericide at 1.56, 25, and >50 µg respectively. Conclusion: Melittin specifically invade the corresponding bacteria and induce significant inhibitory and bactericidal activity against the main agents of bacterial peritonitis. Complementary studies in animal model would be overcome bacterial drug resistance issue specifically in bacterial peritonitis.

  10. Functionalized Activated Carbon Derived from Biomass for Photocatalysis Applications Perspective

    Samira Bagheri

    2015-01-01

    Full Text Available This review highlighted the developments of safe, effective, economic, and environmental friendly catalytic technologies to transform lignocellulosic biomass into the activated carbon (AC. In the photocatalysis applications, this AC can further be used as a support material. The limits of AC productions raised by energy assumption and product selectivity have been uplifted to develop sustainable carbon of the synthesis process, where catalytic conversion is accounted. The catalytic treatment corresponding to mild condition provided a bulk, mesoporous, and nanostructure AC materials. These characteristics of AC materials are necessary for the low energy and efficient photocatalytic system. Due to the excellent oxidizing characteristics, cheapness, and long-term stability, semiconductor materials have been used immensely in photocatalytic reactors. However, in practical, such conductors lead to problems with the separation steps and loss of photocatalytic activity. Therefore, proper attention has been given to develop supported semiconductor catalysts and certain matrixes of carbon materials such as carbon nanotubes, carbon microspheres, carbon nanofibers, carbon black, and activated carbons have been recently considered and reported. AC has been reported as a potential support in photocatalytic systems because it improves the transfer rate of the interface charge and lowers the recombination rate of holes and electrons.

  11. Anti-Influenza Activity of C60 Fullerene Derivatives

    Shoji, Masaki; Takahashi, Etsuhisa; Hatakeyama, Dai; Iwai, Yuma; Morita, Yuka; Shirayama, Riku; Echigo, Noriko; Kido, Hiroshi; Nakamura, Shigeo; Mashino, Tadahiko; Okutani, Takeshi; Kuzuhara, Takashi

    2013-01-01

    The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains a serious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymerase consists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity. Fullere...

  12. Synthesis of geranylhydroquinone derivatives with potential cytotoxic activity

    Natural geranylhydroquinone 1 and geranyl-p-methoxyphenol 2 were prepared by Electrophilic Aromatic Substitution (EAS) reactions between geraniol and 1,4-hydroquinone or p-methoxyphenol respectively, using BF3 ·Et2O as a catalyst. Furthermore, natural geranylquinone 3, geranyl-1,4-dimethoxyquinone 4 and the new geranyl-4-methoxyphenyl acetate 5 were obtained by chemical transformations of 1 and 2. The compounds were evaluated for their in vitro cytotoxicity activities against cultured human cancer cells of PC-3 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma, and Dermal Human ibroblasts DHF. IC50 values were in the μM range. (author)

  13. Infinite dilution activity coefficients of solvents in fatty oil derivatives

    Ferreira, Olga; Foco, Gloria

    2003-01-01

    http://apps.isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=8&SID=V21Di6PajaHLPoM3@AJ&page=1&doc=1&colname=WOS Inverse gas-liquid chromatography has been applied to measure infinite dilution activity coefficients (γ∞) of different solutes in low and high molecular weight triacylglycerides (TAGs) and in mixtures of carboxylic acids with TAGs. The γ∞ data obtained were used to determine binary interaction and size related parameters for the GCA-EOS group contribut...

  14. Anti-inflammatory activity of lupine (Lupinus angustifolius L.) protein hydrolysates in THP-1-derived macrophages

    Millán-Linares, María del Carmen; Bermúdez, Beatriz; Yust, María del Mar; Millán, Francisco; Pedroche, Justo

    2014-01-01

    The effect of two different lupine protein hydrolysates (LPHs) on in vitro macrophage activation in a THP-1-derived macrophage model was investigated. THP-1-derived macrophages were exposed to RPMI medium containing two LPHs obtained by enzymatic hydrolysis using two different proteases: Izyme AL and Alcalase 2.4 L. Cytokine's expression was measured by quantitative PCR. THP-1-derived macrophages exhibited attenuated expression of proinflammatory cytokines (tumor necrosis factor (TNF), IL-6, ...

  15. Physiochemical, Optical and Biological Activity of Chitosan-Chromone Derivative for Biomedical Applications

    Joonseok Koh; Santosh Kumar

    2012-01-01

    This paper describes the physiochemical, optical and biological activity of chitosan-chromone derivative. The chitosan-chromone derivative gels were prepared by reacting chitosan with chromone-3-carbaldehyde, followed by solvent exchange, filtration and drying by evaporation. The identity of Schiff base was confirmed by UV-Vis absorption spectroscopy and Fourier-transform infrared (FTIR) spectroscopy. The chitosan-chromone derivative was evaluated by X-ray diffraction (XRD), thermogravimetric...

  16. Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2009-03-01

    Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5 microg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2 microg/ml) and trypanocidal (16.5 microg/ml) activities, respectively. PMID:19361822

  17. Isolation, Stereochemical Study, and Antioxidant Activity of Benzofuranone Derivatives from a Mangrove-derived Fungus Eurotium rubrum MA-150.

    Meng, Ling-Hong; Mándi, Attila; Li, Xiao-Ming; Liu, Yang; Kurtán, Tibor; Wang, Bin-Gui

    2016-08-01

    Enantiomers of a 2-benzofuran-1(3H)-one derivative [(-)- and (+)-] and four known analogs () were isolated and identified from the culture extract of Eurotium rubrum MA-150, a fungus obtained from the mangrove-derived rizospheric soil. Their structures were established by detailed interpretation of nuclear magnetic resonance (NMR) data and the structure of (±)- was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of the enantiomers (-)- and (+)- was determined by means of online high-performance liquid chromatography - electronic circular dichroism (HPLC-ECD) measurements and time-dependent Density Functional Theory - electronic circular dichroism (TDDFT-ECD) calculations. Compounds (±)- as well as and exhibited potent DPPH radical scavenging activities with IC50 values of 1.23, 2.26, and 3.99 μg/mL, respectively. Chirality 28:581-584, 2016. © 2016 Wiley Periodicals, Inc. PMID:27376714

  18. Plant-Derived Compounds with Potential Sedative and Anxiolytic Activities

    Theresa Ibibia Edewor-Kuponiyi

    2013-07-01

    Full Text Available A wide variety of active phytochemicals such as flavonoids, alkaloids, saponins, etc., have been isolated and identified in different plants. Pharmacological and chemical investigations of medicinal plants have provided important advances in therapeutic approach to several pathologies as well as extremely useful tools for the theoretical study of physiology and pharmacology. With increased use of herbal medicine, medicinal plants are receiving more attention from the scientific and pharmaceutical communities. Several compounds have been isolated and evaluated for their sedative and anxiolytic properties. Although most of the reported works are more of academic interest and very few find entry at clinical trials; one is hopeful that as more discoveries of sedative and anxiolytic compounds from plants are made, it will lead to generation of more effective drugs.

  19. Structure-activity relationship studies of citalopram derivatives

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

    2016-01-01

    . The antidepressant drug citalopram displays high-affinity S1 binding and low-affinity S2 binding. To elucidate a possible therapeutic role of allosteric inhibition of SERT a drug that specifically targets the allosteric site is required. The purpose of this study was to find a compound bearing higher...... selectivity 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...

  20. Synthesis of geranylhydroquinone derivatives with potential cytotoxic activity

    Baeza, Evelyn; Catalan, Karen; Pena-Cortes, Hugo; Espinoza, Luis, E-mail: luis.espinozac@usm.cl [Departamento de Quimica, Universidad Tecnica Federico Santa Maria, Valparaiso (Chile); Villena, Joan [Facultad de Medicina, Universidad de Valparaiso, Centro Regional de Estudios en Alimentos Saludables, Valparaiso (Chile); Carrasco, Hector [Departamento de Ciencias Quimicas, Universidad Andres Bello, Campus Vina del Mar (Chile)

    2012-07-01

    Natural geranylhydroquinone 1 and geranyl-p-methoxyphenol 2 were prepared by Electrophilic Aromatic Substitution (EAS) reactions between geraniol and 1,4-hydroquinone or p-methoxyphenol respectively, using BF{sub 3} {center_dot}Et{sub 2}O as a catalyst. Furthermore, natural geranylquinone 3, geranyl-1,4-dimethoxyquinone 4 and the new geranyl-4-methoxyphenyl acetate 5 were obtained by chemical transformations of 1 and 2. The compounds were evaluated for their in vitro cytotoxicity activities against cultured human cancer cells of PC-3 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma, and Dermal Human ibroblasts DHF. IC{sub 50} values were in the {mu}M range. (author)

  1. Synthesis of geranylhydroquinone derivatives with potencial cytotoxic activity

    Evelyn Baeza

    2012-01-01

    Full Text Available Natural geranylhydroquinone 1 and geranyl-p-methoxyphenol 2 were prepared by Electrophilic Aromatic Substitution (EAS reactions between geraniol and 1,4-hydroquinone or p-methoxyphenol respectively, using BF3∙Et2O as a catalyst. Furthermore, natural geranylquinone 3, geranyl-1,4-dimethoxyquinone 4 and the new geranyl-4-methoxyphenyl acetate 5 were obtained by chemical transformations of 1 and 2. The compounds were evaluated for their in vitro cytotoxicity activities against cultured human cancer cells of PC-3 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma, and Dermal Human Fibroblasts DHF. IC50 values were in the µM range.

  2. Synthesis and in Vitro Cytotoxic Activity Evaluation of (E-16-(Substituted Benzylidene Derivatives of Dehydroepiandrosterone

    Mohsen Vosooghi

    2013-05-01

    Full Text Available Background and the purpose of the study:Modified androsterone derivatives are class of steroidal compounds with potential anticancer properties. Various steroidal derivatives containing substitution at position 16 have shown diversified pharmacological activities. In the present study, a new series of cytotoxic 16-(substituted benzylidene derivatives of dehydroepiandrosterone (DHEA were synthesized and evaluated against three different cancer cell lines.Methods:The cytotoxic 16-(substituted benzylidene derivatives of DHEA were synthesized via aldol condensation of DHEA with corresponding benzaldehyde derivatives. The cytotoxic activity of synthesized derivatives was evaluated against three different cancer cells including KB, T47D and SK-N-MC cell lines by MTT reduction colorimetric assay.Results:The results indicated that 16-(substituted benzylidene derivatives of DHEA could be served as a potent anti-cancer agent. The 3-cholro benzylidene derivatives of DHEA was the most potent synthesized derivative especially against KB and T47D cell lines (IC50 values were 0.6 and 1.7 μM; respectively.Conclusion:The cytotoxic potential of novel benzylidene derivatives of DHEA is mainly attributed to the position and nature of the substituted group on the benzylidene pendant

  3. Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

    Juan Shen; Jing Bo Shi; Fei Hu Chen; Yuan Wang; Jing Jing Ruan; Yua Huang

    2009-01-01

    A series of retinoate and retinamide derivatives were designed, synthesized, and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays (FCM). All compounds showed cytotoxicity, especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-traus retinoic acid (ATRA). Furthermore, compound ld could induce NB4 cell lines differentiation efficiently.

  4. Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

    Synthesis of chalcones and 2-pyrazoline derivatives has been an active field of research due to the established pharmacological effects of these compounds. In this study, a series of chalcone (1a-i), 2-pyrazoline-1-carbothioamides (2a-i) and 2-pyrazoline-1-carboxamide derivatives (3a-g) were synthes...

  5. Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol

    Emerson Silva Lima

    2012-12-01

    Full Text Available 4-nerolidylcatechol (4-NC is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast, however 4-NC was more cytotoxic (IC50 = 31.4 µM and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at −20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at −20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds.

  6. Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A.

    Girolami, R. L.; Stamm, J M

    1980-01-01

    The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staphylococcus aureus, with ODMF most active against Proteus mirabilis, indole-positive Proteus, and Providencia and gentamicin most active against other species. Activity of each of ...

  7. Synthesis of Some New Thiazole Derivatives and Their Biological Activity Evaluation

    Leyla Yurttaş

    2015-01-01

    Full Text Available New 2-(4-arylpiperazine-1-yl-N-[4-(2-(4-substituted phenylthiazol-4-ylphenyl]acetamide derivatives were synthesized and evaluated for their antimicrobial and anticholinesterase activities. Acetylcholinesterase inhibitory activities of the compounds were found weak contrary to expectations. It is unlikely that antifungal activity of the compounds was found significant, especially against Candida parapsilosis.

  8. Synthesis of New Thiazole Derivatives Bearing A Sulfonamide Moiety Of Expected Anticancer And Radiosensitizing Activities

    In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new pyrano thiazole and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

  9. Synthesis and Anti-influenza Virus Activity of Ethyl 6-Bromo-5-hydroxyindole-3-carboxylate Derivatives

    Yan Fang ZHAO; Jin Hua DONG; Ping GONG

    2004-01-01

    A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.

  10. Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives.

    Guimarães, Keller G; de Freitas, Rossimiriam P; Ruiz, Ana L T G; Fiorito, Giovanna F; de Carvalho, João E; da Cunha, Elaine F F; Ramalho, Teodorico C; Alves, Rosemeire B

    2016-03-23

    A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL(-1)). This compound represents a promising matrix for developing new antiproliferative agents. PMID:26859070

  11. The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

    Marina Azevedo Souza

    2013-05-01

    Full Text Available Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively. In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.

  12. The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

    Souza, Marina Azevêdo; Johann, Susana; Lima, Luciana Alves Rodrigues dos Santos; Campos, Fernanda Fraga; Mendes, Isolda Castro; Beraldo, Heloisa; de Souza-Fagundes, Elaine Maria; Cisalpino, Patrícia Silva; Rosa, Carlos Augusto; Alves, Tânia Maria de Almeida; de Sá, Nívea Pereira; Zani, Carlos Leomar

    2013-01-01

    Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes. PMID:23778660

  13. Antibacterial Characteristics and Activity of Water-Soluble Chitosan Derivatives Prepared by the Maillard Reaction

    Ying-Chien Chung; Cheng-Fang Tsai; Jan-Ying Yeh

    2011-01-01

    The antibacterial activity of water-soluble chitosan derivatives prepared by Maillard reactions against Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Escherichia coli, Shigella dysenteriae, and Salmonella typhimurium was examined. Relatively high antibacterial activity against various microorganisms was noted for the chitosan-glucosamine derivative as compared to the acid-soluble chitosan. In addition, it was found that the susceptibility of the test organisms to the water-s...

  14. The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

    Marina Azevedo Souza; Susana Johann; Luciana Alves Rodrigues dos Santos Lima; Fernanda Fraga Campos; Isolda Castro Mendes; Heloisa Beraldo; Elaine Maria de Souza-Fagundes; Patricia Silva Cisalpino; Carlos Augusto Rosa; Tania Maria de Almeida Alves; Nivea Pereira de Sa; Carlos Leomar Zani

    2013-01-01

    Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone an...

  15. Antitrypanosomal Activity of Novel Benzaldehyde-Thiosemicarbazone Derivatives from Kaurenoic Acid †

    2011-01-01

    A series of new thiosemicarbazones derived from natural diterpene kaurenoic acid were synthesized and tested against the epimastigote forms of Trypanosoma cruzi to evaluate their antitrypanosomal potential. Seven of the synthesized thiosemicarbazones were more active than kaurenoic acid with IC50 values between 2-24.0 mM. The o-nitro-benzaldehyde-thiosemicarbazone derivative was the most active compound with IC50 of 2.0 mM. The results show that the structural modifications accomplished enhan...

  16. The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

    2013-01-01

    Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazo...

  17. Synthesis of Urea based Chalcone Derivatives and Evaluate its Biological Activity

    Arpita Desai

    2016-05-01

    Full Text Available Chalcones have been the center of attraction for researchers from several decades due to nits innumerous therapeutic application, Efforts have been done in my research to synthesized chalcones and their derivatives that further reacts with various substituted aldehyde to give corresponding substituted chalcone derivatives. Now these derivatives on condensation with Guanidine nitrate gives the vast range of phenyl pyrimidine amine Derivatives. Structure elucidation of synthesized compound had been made on the basis of element analysis, 1H NMR Spectra studies. The microbial activity of the synthesized compounds has been studied against the species bacillus subtillis, staphylococcus aureus, Escherichia coli, and salmonella typhi.

  18. Anthrarobin and its derivatives: evaluation of antibacterial and lipoxygenase inhibition activities

    The antibacterial activity of anthrarobin and its synthesized derivatives 1, 10-dihydoxyanthracen-2-0-acetate (1) and anthracen-1, 2-10-tri-O-acetate (2) is determined against two Gram-negative bacteria (Escherichia coli, Pseudomonas aerogenosa) and two Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) along with the lipoxygenase inhibition activity. Gentamycin (0.3 %) was used as standard antibiotic for antibacterial assay. The minimum inhibitory concentration (MIC) was determined by agar well diffusion method. Anthrarobin showed highest antibacterial activity against all the tested bacteria while anthracen-1, 2-10-tri-0-acetate (2) exhibited 97 % activity against Gram-positive bacteria, Staphylococcus aureus, and; 36 % activity against Gram-negative bacteria Escherichia coli. On the other hand, 1, 10-dihydoxyanthracen-2-0-acetate (1) remained non-significant against all the bacteria tested. When anthrarobin and its derivatives were analyzed for lipoxygenase inhibition studies, only anthrarobin showed weak inhibition activity with IC50 value of 65.2 μM. It is concluded that anthrarobin has significant potential for antibacterial activity as compared to its synthesized derivatives. Structure-activity relationship suggests that numbers of hydroxyl group in anthrarobin may be responsible for antimicrobial activity and the activity decreases with the substitution of acyl groups in synthesized derivatives. (author)

  19. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    Figueroa-Valverde Lauro

    2014-01-01

    Full Text Available Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R. Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases P=0.05 the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM; however, this phenomenon was significantly inhibited P=0.06 by indomethacin and PINANE-TXA2  P=0.05 at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation.

  20. Design and synthesis of novel Y-shaped barbituric acid derivatives as PPARγ activators.

    Dixit, Vaibhav A; Rathi, Prakash Chandra; Bhagat, Shweta; Gohlke, Holger; Petersen, Rasmus K; Kristiansen, Karsten; Chakraborti, Asit K; Bharatam, Prasad V

    2016-01-27

    Novel Y-shaped barbituric acid (BA) derivatives have been designed using rational methods including molecular docking. Fourteen novel compounds were synthesized using hydroxyl group protection-deprotection strategies for PPARγ activation. Competitive binding analysis of the synthesized molecules using time-resolved fluorescence resonance energy transfer (FRET) method was carried out, and the IC50 values were determined. The symmetrically substituted derivatives have shown greater binding affinity than unsymmetrically substituted derivatives. Nitrobenzyl and cyanophenyl substituted derivatives have shown reasonable binding affinities (10.1 and 6.5 μM, respectively), while mono and diacetate derivatives were found inactive. Molecular dynamics simulations show that the designed compounds have interaction profiles similar to partial agonists. The most significant finding of our study is that BA derivatives with symmetrically substituted weakly polar side chains result in the desired moderate level of PPARγ binding affinities. PMID:26708109

  1. In Vitro Antioxidant Activities of Sulfated Derivatives of Polysaccharides Extracted from Auricularia auricular

    Zhang, Hua; Wang, Zhen-Yu; Yang, Lin; Yang, Xin; Wang, Xue; Zhang, Zhi

    2011-01-01

    In this research, two types of sulfated polysaccharide derivatives were successfully synthesized. Their antioxidant activities were investigated by employing various established in vitro systems. In addition, the degree of sulfation was evaluated using ion-chromatography and IR spectra. The results verify that, when employing scavenging superoxide radical tests, both the sulfation of acid Auricularia auricular polysaccharides (SAAAP) and the sulfation of neutral Auricularia auricular polysaccharides (SNAAP) derivatives possessed considerable antioxidant activity and had a more powerful antioxidant competence than that of the native non-sulfated polysaccharides (AAAP and NAAP). On the other hand, AAAP and NAAP exhibited stronger activity on scavenging both the hydroxyl radical and lipid peroxidation. Available data obtained with in vitro measurements indicates that the sulfated groups of AAAP and NAAP played an important role on antioxidant activity. In sum, the research demonstrates that the antioxidant activity of sulfated polysaccharide derivatives in vitro has a potential significance for seeking new natural antioxidant protective agents. PMID:21686185

  2. Synthesis of Novel Pyrimethanil Grafted Chitosan Derivatives with Enhanced Antifungal Activity

    Liu, Song; Xing, Ronge; Chen, Xiaolin

    2016-01-01

    In this study, three pyrimethanil grafted chitosan (PML-g-CS) derivatives were obtained. The structures of the conjugates were confirmed by FT-IR, 1H NMR, and EA. The grafting ratios were measured by HPLC. Antifungal properties of pyrimethanil grafted chitosan (PML-g-CS) derivatives against the plant pathogenic fungi Rhizoctonia solani and Gibberella zeae were investigated at concentrations of 100, 200, and 400 mg/L. The PML-g-CS derivatives showed enhanced antifungal activity in comparison with chitosan. The PML-g-CS-1 showed the best antifungal activity against R. solani, whose antifungal index was 58.32%. The PML-g-CS-2 showed the best antifungal activity against G. zeae, whose antifungal index was 53.48%. The conjugation of chitosan and pyrimethanil showed synergistic effect. The PML-g-CS derivatives we developed showed potential for further study and application in crop protection. PMID:27529072

  3. Synthesis, Larvicidal Activities and Antifungal Activities of Novel Chlorantraniliprole Derivatives and Their Target in the Ryanodine Receptor

    Qichao Chen

    2015-03-01

    Full Text Available In order to identify novel chlorantraniliprole derivatives as potential insecticides or fungicides, 25 analogues of chlorantraniliprole were synthesized. The insecticidal activities against oriental armyworm and the antifungal activities against five typical fungi of these derivatives were tested. Compounds 2u, 2x and 2y exhibited good activities against oriental armyworm, especially compounds 2u and 2x which showed higher larvicidal activities than indoxacarb. Moreover, all of the tested compounds exhibited activities against five typical fungi. The Ki values of all synthesized compounds were calculated using AutoDock4. The relationship between the Ki values and the results of insecticidal activities against oriental armyworm further indicated that the membrane-spanning domain protein of the ryanodine receptor might contain chlorantraniliprole binding sites.

  4. Synthesis and anti-inflammatory activity of imidazo [1,2-a] pyrimidine derivatives

    Jin Pei Zhou; Yi Wei Ding; Hui Bin Zhang; Lian Xu; Yue Dai

    2008-01-01

    A series of imidazo [1,2-a] pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.

  5. Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido [5,4-c] quinoline derivatives

    Fan Zhang; Xin Zhai; Li Juan Chen; Jian Guo Qi; Bo Cui; Yu Cheng Gu; Ping Gong

    2011-01-01

    A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro. It was found that most of the tested compounds especially compound 17, shown stronger activity to the selected three cell lines than ZM447439.

  6. Novel 2-Chloro-8-arylthiomethyldipyridodiazepinone Derivatives with Activity against HIV-1 Reverse Transcriptase

    Supanna Techasakul

    2007-02-01

    Full Text Available Based on the molecular modeling analysis against Y181CHIV-1 RT, dipyridodiazepinone derivatives containing an unsubstituted lactamnitrogen and 2-chloro-8-arylthiomethyl were synthesized via an efficientroute. Some of them were evaluated for their antiviral activity against HIV-1RT subtype E and were found to exhibit virustatic activity comparable to some clinically usedtherapeutic agents.

  7. Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds.

    Artini, M; Papa, R; Barbato, G; Scoarughi, G L; Cellini, A; Morazzoni, P; Bombardelli, E; Selan, L

    2012-01-15

    Use of herbal plant remedies to treat infectious diseases is a common practice in many countries in traditional and alternative medicine. However to date there are only few antimicrobial agents derived from botanics. Based on microbiological screening tests of crude plant extracts we identified four compounds derived from Krameria, Aesculus hippocastanum and Chelidonium majus that showed a potentially interesting antimicrobial activity. In this work we present an in depth characterization of the inhibition activity of these pure compounds on the formation of biofilm of Staphylococcus aureus as well as of Staphylococcus epidermidis strains. We show that two of these compounds possess interesting potential to become active principles of new drugs. PMID:22182580

  8. Structures and antiviral activities of butyrolactone derivatives isolated from Aspergillus terreus MXH-23

    Ma, Xinhua; Zhu, Tianjiao; Gu, Qianqun; Xi, Rui; Wang, Wei; Li, Dehai

    2014-12-01

    A new butyrolactone derivative, namely butyrolactone VIII ( 1), and six known butyrolactones ( 2-7) were separated from the ethyl acetate (EtOAc) extract of the fermentation broth of a fungus, Aspergillus terreus MXH-23. The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance (NMR) and mass spectrometry (MS). Known butyrolactone derivatives contain an α, β-unsaturated γ-lactone ring with α-hydroxyl and γ-benzyl, and butyrolactone VIII ( 1) was the first butyrolactones contains α-benzyl and γ-hydroxyl on α, β-unsaturated lactone ring. All of the butyrolactone derivatives were tested for their anti-influenza (H1N1) effects. Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified, derivative 1, did not.

  9. Sulfonamide and carbamate derivatives of 6-chloropurine: synthesis, characterization and antimicrobial activity evaluation

    K. Venkata Narayana

    2016-07-01

    Full Text Available A series of new sulfonamide derivatives, 9-(substitutedbenzenesulfonyl-6-chloro-9H-purines 7(a-e and carbamate derivatives, 6-chloro-purine-9-carboxylic acid substituted alkyl/arylester 9(a-d, have been synthesized through an intermediate, sodium salt of 6-chloro-9(H-purine (6 which was prepared by the treatment of 6-chloro-9(H-purine (4 with sodium hydride. Structures of the newly synthesized compounds were elucidated by IR, NMR ( 1H and 13C, mass spectra and elemental analysis. Antimicrobial activity against three bacterial strains and three fungal strains at two different concentrations, 100 and 200 µg/mL including MIC values was investigated. Bio-screening data disclosed that most of the sulfonamide derivatives, 7a, 7c and 7d, and one carbamate derivative 9a showed promising antimicrobial activity having MIC values in the range of 18.0-25.0 µg/mL.

  10. Structure-function activity of dehydrozingerone and its derivatives as antioxidant and antimicrobial compounds.

    Kubra, Ismail Rahath; Bettadaiah, Bheemanakere Kempaiah; Murthy, Pushpa Srinivas; Rao, Lingamallu Jagan Mohan

    2014-02-01

    Dehydrozingerone, structural half analogue of curcumin, is a phenolic compound isolated from ginger (Zingiber officinale) rhizomes. Dehydrozingerone and several of its derivatives such as glucopyranosides and its tetra acetate derivative and 4-O-acetyl and methyl derivatives of dehydrozingerone were synthesized in the present study. Dehydrozingerone, synthesised with improved yield was used for the synthesis of Dehydrozingerone 4-O-β-D-glucopyranoside (first time report) by modified Koenigs-Knorr-Zemplén method. Structures of all the compounds have been established using spectroscopic methods. These compounds were tested for radical scavenging activity by DPPH and FRAP method as well as for antibacterial and antifungal activities. The parent molecule exhibited better scavenging activity as compared to its derivatives indicating the significance of free phenolic hydroxyl group. Also, Dehydrozingerone and its derivatives exhibited antibacterial as well as antifungal activity due to the conjugation system present, which includes α,β-unsaturated carbonyl (C = O) group. This study gave an insight into structural requirements for dehydrozingerone activity. PMID:24493881

  11. Antitumor activity of placenta-derived mesenchymal stem cells producing pigment epithelium-derived factor in a mouse melanoma model.

    Chen, Qiaoling; Cheng, Ping; Song, Na; Yin, Tao; He, Hong; Yang, Li; Chen, Xiancheng; Wei, Yuquan

    2012-09-01

    Mesenchymal stem cells (MSCs) are a new tool that can be used for the delivery of therapeutic agents to tumor cells. Among the various types of MSCs, placenta-derived MSCs (PDMSCs) have emerged as one of the most attractive vehicles for gene therapy due to their high throughput, lack of ethical concerns, non-invasive procedure for their harvesting and ease of isolation. In this study, we evaluated the antitumor activity of human PDMSCs loaded with recombinant adenoviruses expressing pigment epithelium-derived factor (PEDF). PDMSCs were transduced with adenovirus PEDF and the expression of PEDF was confirmed by western blotting and ELISA. The inhibition of angiogenesis mediated by PEDF-expressing PDMSCs (PDMSC-PEDF) was determined using human umbilical vein endothelial cell (HUVEC) proliferation inhibition assay and migration inhibition assay in vitro. In in vivo experiments, C57BL/6 mice bearing B16-F10 melanoma were treated with intratumoral injection of PDMSC-PEDF twice at a 4-day interval. The tumor volume and weight were recorded. The results demonstrated that the administration of PDMSC-PEDF resulted in marked suppression of tumor growth in an established melanoma model, which was associated with a decreased number of microvessels and increased apoptosis of tumor cells compared with the controls. The results suggest that human PDMSCs have potential use as effective delivery vehicles for cancer gene therapy. PMID:23741242

  12. Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities.

    Beteck, Richard M; Coertzen, Dina; Smit, Frans J; Birkholtz, Lyn-Marie; Haynes, Richard K; N'Da, David D

    2016-07-01

    As part of a programme aimed at identifying rational new triple drug combinations for treatment of malaria, tuberculosis and toxoplasmosis, we have selected quinolones as one component, given that selected examples exhibit exceptionally good activities against the causative pathogens of the foregoing diseases. The quinolone decoquinate (DQ), an old and inexpensive coccidiostat, displays anti-malarial activity in vitro against Plasmodium falciparum (Pf). However, because of its exceedingly poor solubility in water or organic solvents, development of DQ as a drug is problematical. We have therefore converted DQ in straightforward fashion into tractable new derivatives that display good activities in vitro against chloroquine-sensitive NF54 and multidrug-resistant K1 and W2 Pf, and relatively low toxicities against human fibroblast cells. The most active compound, the N-acetyl derivative 30, is 5-fold more active than DQ against NF54 and K1 and equipotent with DQ against W2. It possesses an activity profile against all strains comparable with that of the artemisinin derivative artesunate. Overall, this compound and the other accessible and active derivatives serve as an attractive template for development of new and economic lead quinolones. PMID:27210430

  13. Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

    A C60-based ebselen derivative 4 was synthesized through the cycloaddition of C60 with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C60). Its structure was characterized by 1H NMR, 13C NMR, IR, UV, and FAB-MS. To verify that the C60-based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C60 derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C60-based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 μmol/L), the results showed that the antioxidative and protective potencies of the C60-based ebselen derivative 4 (MTT (OD) 0.340 ± 0.035, LDH release (UL-1) 4.80 ± 0.16) against H2O2-mediated neuronal injury have an advantage over those of C60 derivative 5 (MTT (OD) 0.297 ± 0.036, LDH release (UL-1) 5.37 ± 0.31) and ebselen derivative 6 (MTT (OD) 0.267 ± 0.027, LDH release (UL-1) 5.85 ± 0.26). Correspondingly, the GPX activity of 4 (1.62 U/μmol) was higher than that of 5 (0.77 U/μmol) and 6 (1.24 U/μmol). These findings demonstrate that the incorporation of two components with similar biological activity (C60 component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C60-based compound. (author)

  14. Design, Synthesis and Antitumor Activity of Fluoroquinolone C3 Heterocyclic Bis-oxadiazole Methylsulfide Derivatives Derived from Levofloxacin

    HU Guo-qiang; WANG Guo-qiang; DUAN Nan-nan; WEN Xiao-yi; CAO Tie-yao; XIE Song-qiang; HUANG Wen-long

    2012-01-01

    To discover an efficient route for the shift from an antibacterial fluoroquinolone to an antitumor one based on the mechanistic similarities between targeting topoisomerases and the eukaryotic ones,two series of the title compounds,C3 bis-oxadiazole methylsulfides 6a-6h and corresponding dimethylpiperazinium iodides 7a-7h derived from levofloxacin 1 were designed and synthesized.Their in vitro antiproliferative activities against Chinese hamster ovary cell line(CHO),murine leukemia cell line(Ll 210) and human leukocytoma cell line(HL60) were evaluated by MTT assay,and inhibitory effect on DNA topoisomerase Ⅱα was also measured by means of densitometric assay.

  15. Palladium-Catalyzed C–C Bond Formations via Activation of Carboxylic Acids and Their Derivatives

    Song, Bingrui

    2013-01-01

    Applications of carboxylic acids and their derivatives in transition metal-catalyzed cross-coupling reactions regio-selectively forming Csp3-Csp2, and Csp2-Csp2 bonds were explored in this thesis. Several important organic building blocks such as aryl acetates, diaryl acetates, imines, ketones, biaryls, styrenes and polysubstituted alkenes were successfully accessed from carboxylic acids and their derivatives by the means of C–H activation and decarboxylative cross-couplings. An efficient ...

  16. Synthesis of Benzofuran Derivatives via Rearrangement and Their Inhibitory Activity on Acetylcholinesterase

    Ling-Yi Kong

    2010-11-01

    Full Text Available During a synthesis of coumarins to obtain new candidates for treating Alzheimer’s Disease (AD, an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil.

  17. IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

    Kuppusamy Asokkumar; Lokeswari Prathyusha Tangella; Muthusamy Umamaheshwari; Thirumalaisamy Shivashanmugam; Varadharajan Subhadradevi; Puliyath Jagannath; Arumugam Madeswaran

    2012-01-01

    Objective Soluble epoxide hydrolase (sEH) belongs to the α/β -hydrolase superfamily, a subclass of α/β proteins. Chalcones are chemical compounds that show hopeful obliging efficacy in controlling numerous diseases. The main objective of the study is to evaluate the sEH inhibitory activity of some synthesized chalcone derivatives and identification of its mode of inhibition. Methods Four different chalcone derivatives (PC-1 to PC-4) were selected for synthesis by Claisen-Schmidt method. The i...

  18. A simple synthesis of kaurenoic esters and other derivatives and evaluation of their antifungal activity

    Representative esters derived from kaurenoic acid were prepared in order to evaluate their antifungal properties. Alkyl and substituted benzyl esters were obtained in good yield under mild conditions by esterification of kaurenoic acid with the corresponding alkyl halide in KOH-acetone. All synthesized compounds were tested for antifungal properties against pathogenic yeasts, hialohyphomycetes and dermatophytes. Kaurenoic acid and derivatives containing a free carboxyl group were moderately active against dermatophytes. (author)

  19. Synthesis and evaluation of acetylcholineesterase inhibitory potential and antioxidant activity of benzothiazine derivatives

    Shahwar, Durre; SANA, Uzma; Ahmad, Naeem

    2013-01-01

    The aim of the present study was to synthesize and characterize benzothiazine derivatives prepared by using 2-aminothiophenol and saccharine and in vitro screen their enzyme inhibition and antioxidant potential. Nine different derivatives were prepared and their structures were confirmed by spectral studies (EIMS, 1 H and 13C NMR). Enzyme inhibition potential of the synthesized compounds was evaluated by Ellman's method, while antioxidant activity was determined by DPPH and FRAP...

  20. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  1. Synthesis, Anti-Inflammatory and Anti-oxidant activity of some substituted Benzimidazole Derivatives

    Rajasekaran S; Abhiskek Chatterjee; Gopalkrishna Rao

    2012-01-01

    Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-fungal, antitumor and anthelmintic activity. In addition, few N-substituted benzimidazole derivatives have shown to exhibit significant activity against several viruses, including HIV, herpes simplex (HSV-1), influenza, picorna, human cytomegalovirus (HCMV) and hepatitis C virus. The five membered heterocyclic moiety 1,3,4-oxadiazole also confers for ...

  2. Synthesis and Antimicrobial Activity ofSome New Thioether Derivatives of Quinoxaline

    Singh, D. C. P.; S. R. Hashim; Singhal, R. G.

    2011-01-01

    2-Chloro-3-methylquinoxaline was selected as nucleus around which the molecular manipulations were carried out to get new compounds expected to possess better anti microbial activity. Various quinoxaline derivatives have been synthesized by replacing the chlorine at C-2 with a thioether linkage, which in turn attached to 2-(N-(substituted phenyl)acetamides. The synthesized compounds (5) were tested for their antimicrobial activity. Compounds 5b, 5c, 5d and 5i were found most active (comparabl...

  3. Synthesis and Immunosuppressive Activity of New Amino Alcohol Derivatives(Ⅰ)

    MI Hao-yu; CUI Lin-lin; ZHANG Qun-li; LI Fang; JIANG Tao; LIANG Yong-tao; WANG En-si

    2011-01-01

    A series of new amino alcohol derivatives was synthesized and evaluated for their immunosuppressive activity on mouse peripheral blood lymphocytes.The structures were confirmed by means of 1H NMR,13C NMR,IR and MS.Most of the compounds display moderate to potent inhibitory activity.Compound 9d shows the most activity among them that are expected as a powerful candidate for safer immunosuppressant for organ transplantations and the treatment of autoimmune diseases.

  4. Physicochemical Properties That Enhance Discriminative Antibacterial Activity of Short Dermaseptin Derivatives

    Rotem, Shahar; Radzishevsky, Inna; Mor, Amram

    2006-01-01

    Antimicrobial peptides are widely believed to exert their effects by nonspecific mechanisms. We assessed the extent to which physicochemical properties can be exploited to promote discriminative activity by manipulating the N-terminal sequence of the 13-mer dermaseptin derivative K4-S4(1-13) (P). Inhibitory activity determined in culture media against 16 strains of bacteria showed that when its hydrophobicity and charge were changed, P became predominantly active against either gram-positive ...

  5. Myeloid-derived Suppressor Cells Inhibit T Cell Activation by Depleting Cystine and Cysteine

    Minu K Srivastava; Sinha, Pratima; Clements, Virginia K.; Rodriguez, Paulo; Ostrand-Rosenberg, Suzanne

    2009-01-01

    Myeloid-derived suppressor cells (MDSC) are present in most cancer patients and are potent inhibitors of T-cell-mediated anti-tumor immunity. Their inhibitory activity is attributed to production of arginase, reactive oxygen species, inducible nitric oxide synthase, and IL-10. We now report that MDSC also block T cell activation by sequestering cystine and limiting the availability of cysteine. Cysteine is an essential amino acid for T cell activation because T cells lack cystathionase, which...

  6. Anticancer, Anti-Inflammatory, and Analgesic Activities of Synthesized 2-(Substituted phenoxy) Acetamide Derivatives

    Priyanka Rani; Dilipkumar Pal; Rahul Rama Hegde; Syed Riaz Hashim

    2014-01-01

    The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy)-N-(1-phenylethyl)acetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer), SK-N-SH (neuroblastoma), anti-inflammatory activity, and analgesic activ...

  7. Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

    Santos, Mauricio S. dos; Gomes, Adriana O.; Bernardino, Alice M.R.; Souza, Marcos C. de, E-mail: alicerolim@globo.co [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Programa de Pos-Graduacao em Quimica Organica; Khan, Misbahul A. [The Islamia University of Bahawalpur (Pakistan). Chemistry Dept.; Brito, Monique A. de [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Fac. de Farmacia. Lab. de Quimica Medicinal Computacional; Castro, Helena C.; Abreu, Paula A. [Universidade Federal Fluminense (LABioMol/GCM/UFF), Niteroi, RJ (Brazil). Inst. de Biologia. Lab. de Antibioticos, Bioquimica e Modelagem Molecular; Rodrigues, Carlos R. [Universidade Federal do Rio de Janeiro (ModMol/UFRJ), RJ (Brazil). Fac. de Farmacia. Lab. de Modelagem Molecular e QSAR; Leo, Rosa M.M. de; Leon, Leonor L.; Canto-Cavalheiro, Marilene M. [Fundacao Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto Oswaldo Cruz. Lab. de Bioquimica de Tripanosomatideos

    2011-07-01

    Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

  8. Synthesis, evaluation, and metabolism of novel [6]-shogaol derivatives as potent Nrf2 activators.

    Zhu, Yingdong; Wang, Pei; Zhao, Yantao; Yang, Chun; Clark, Anderson; Leung, TinChung; Chen, Xiaoxin; Sang, Shengmin

    2016-06-01

    Oxidative stress is a central component of many chronic diseases. The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2 p45-related factor 2 (Nrf2) system is a major regulatory pathway of cytoprotective genes against oxidative and electrophilic stress. Activation of the Nrf2 pathway plays crucial roles in the chemopreventive effects of various inducers. In this study, we developed a novel class of potent Nrf2 activators derived from ginger compound, [6]-shogaol (6S), using the Tg[glutathione S-transferase pi 1 (gstp1):green fluorescent protein (GFP)] transgenic zebrafish model. Investigation of structure-activity relationships of 6S derivatives indicates that the combination of an α,β-unsaturated carbonyl entity and a catechol moiety in one compound enhances the Tg(gstp1:GFP) fluorescence signal in zebrafish embryos. Chemical reaction and in vivo metabolism studies of the four most potent 6S derivatives showed that both α,β-unsaturated carbonyl entity and catechol moiety act as major active groups for conjugation with the sulfhydryl groups of the cysteine residues. In addition, we further demonstrated that 6S derivatives increased the expression of Nrf2 downstream target, heme oxygenase-1, in both a dose- and time-dependent manner. These results suggest that α,β-unsaturated carbonyl entity and catechol moiety of 6S derivatives may react with the cysteine residues of Keap1, disrupting the Keap1-Nrf2 complex, thereby liberating and activating Nrf2. Our findings of natural product-derived Nrf2 activators lead to design options of potent Nrf2 activators for further optimization. PMID:27021962

  9. Semisynthesis, cytotoxic activity, and oral availability of new lipophilic 9-substituted camptothecin derivatives.

    Rodriguez-Berna, Guillermo; Cabañas, Maria Jose Díaz; Mangas-Sanjuán, Victor; Gonzalez-Alvarez, Marta; Gonzalez-Alvarez, Isabel; Abasolo, Ibane; Schwartz, Simó; Bermejo, Marival; Corma, Avelino

    2013-07-11

    Despite that 9-substituted camptothecins are promising candidates in cancer therapy, the limited accessibility to this position has reduced the studies of these derivatives to a few standard modifications. We report herein a novel semisynthetic route based on the Tscherniac-Einhorn reaction to synthesize new lipophilic camptothecin derivatives with amidomethyl and imidomethyl substitutions in position 9. Compounds were evaluated for their antiproliferative activity, topoisomerase I inhibition, and oral availability. Preliminary data demonstrated that bulky imidomethyl modification is an appropriate lipophilic substitution for an effective oral administration relative to topotecan. In addition, this general procedure paves the way for obtaining new camptothecin derivatives. PMID:24900725

  10. A new phloroglucinol derivative from Hypericum calycinum with antifungal and in vitro antimalarial activity.

    Decosterd, L A; Hoffmann, E; Kyburz, R; Bray, D; Hostettmann, K

    1991-12-01

    The new phloroglucinol derivative 1 has been isolated from the light petroleum ether extract of the aerial parts of Hypericum calycinum. Its structure has been established by means of 1H- and 13C-NMR spectroscopy and by nOe, MHQC, and HMBC experiments on its monomethyl ether derivative 3. Compound 1 was fungicidal against Cladosporium cucumerinum in a TLC bioassay. In addition, this new phloroglucinol derivative was also found to exert an interesting antimalarial activity in an in vitro test system. PMID:1818346

  11. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

    Ruzica Livaja Koshiar

    Full Text Available Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte-derived

  12. Antitrypanosomal Activity of Novel Benzaldehyde-Thiosemicarbazone Derivatives from Kaurenoic Acid †

    Cecília M. A. de Oliveira

    2011-01-01

    Full Text Available A series of new thiosemicarbazones derived from natural diterpene kaurenoic acid were synthesized and tested against the epimastigote forms of Trypanosoma cruzi to evaluate their antitrypanosomal potential. Seven of the synthesized thiosemicarbazones were more active than kaurenoic acid with IC50 values between 2-24.0 mM. The o-nitro-benzaldehyde-thiosemicarbazone derivative was the most active compound with IC50 of 2.0 mM. The results show that the structural modifications accomplished enhanced the antitrypanosomal activity of these compounds. Besides, the thiocyanate, thiosemicarbazide and the p- methyl, p-methoxy, p-dimethylamine, m-nitro and o-chlorobenzaldehyde-thiosemicarbazone derivatives displayed lower toxicity for LLMCK2 cells than kaurenoic acid, exhibing an IC50 of 59.5 mM.

  13. Anticancer activity studies of cubebin isolated from Piper cubeba and its synthetic derivatives.

    Rajalekshmi, Dhanya S; Kabeer, Farha A; Madhusoodhanan, Arya R; Bahulayan, Arun K; Prathapan, Remani; Prakasan, Nisha; Varughese, Sunil; Nair, Mangalam S

    2016-04-01

    (-)-Cubebin, isolated from the seeds of Piper cubeba, and its five different types of derivatives (a total of 17), with varying functionalities, were tested for their in vitro anticancer activity against six human cancer cell lines (A549, K562, SiHa, KB, HCT116 and HT29) using MTT assay. Cubebin as well as its derivatives containing lactone and amide groups showed significant anticancer activity. In some of the tested cell lines, the amide derivatives showed higher activity. Morphological analysis indicated that these compounds act through apoptosis mediated pathway of cell death and we expect that these results will pave new paths in the development of novel anticancer agents by the derivatization of (-)-cubebin. PMID:26916436

  14. Synthesis and antileishmanial activity of C7- and C12-functionalized dehydroabietylamine derivatives.

    Dea-Ayuela, M Auxiliadora; Bilbao-Ramos, Pablo; Bolás-Fernández, Francisco; González-Cardenete, Miguel A

    2016-10-01

    Abietane-type diterpenoids, either naturally occurring or synthetic, have shown a wide range of pharmacological actions, including antiprotozoal properties. In this study, we report on the antileishmanial evaluation of a series of (+)-dehydroabietylamine derivatives functionalized at C7 and/or C12. Thus, the activity in vitro against Leishmania infantum, Leishmania donovani, Leishmania amazonensis and Leishmania guyanensis, was studied. Most of the benzamide derivatives showed activities at low micromolar concentration against cultured promastigotes of Leishmania spp. (IC50 = 2.2-46.8 μM), without cytotoxicity on J774 macrophage cells. Compound 15, an acetamide, was found to be the most active leishmanicidal agent, though it presented some cytotoxicity on J774 cells. Among the benzamide derivatives, compounds 8 and 10, were also active against L. infantum intracellular amastigotes, being 18- and 23-fold more potent than the reference compound miltefosine, respectively. Some structure-activity relationships have been identified for the antileishmanial activity in these dehydroabietylamine derivatives. PMID:27318121

  15. Structure–anticancer activity relationships among 4-azolidinone-3-carboxylic acids derivatives

    Lesyk R. B.

    2010-04-01

    Full Text Available The aim of present research was investigation of anticancer activity of 4-azolidinone-3-carboxylic acids derivatives, and studies of structure–activity relationships (SAR aspects. Methods. Organic synthesis; spectral methods; anticancer screening was performed according to the US NCI protocol (Developmental Therapeutic Program. Results. The data of new 4-thiazolidinone-3-alkanecarboxylic acids derivatives in vitro anticancer activity were described. The most active compounds which belong to 5-arylidene-2,4- thia(imidazolidinone-3-alkanecarboxylic acids; 5-aryl(heterylidenerhodanine-3-succinic acids derivatives were selected. Determination of some SAR aspects which allowed to determine directions in lead- compounds structure optimization, as well as desirable molecular fragments for design of potential anticancer agents based on 4-azolidinone scaffold were performed. 5-Arylidenehydantoin-3-acetic acids amides were identified as a new class of significant selective antileukemic agents. Possible pharmacophore scaffold of 5-ylidenerhodanine-3-succinic acids derivatives was suggested. Conclusions. The series of active compounds with high anticancer activity and/or selectivity levels were selected. Some SAR aspects were determined and structure design directions were proposed.

  16. Activated carbons derived from oil palm empty-fruit bunches: application to environmental problems.

    Alam, Md Zahangir; Muyibi, Suleyman A; Mansor, Mariatul F; Wahid, Radziah

    2007-01-01

    Activated carbons derived from oil palm empty fruit bunches (EFB) were investigated to find the suitability of its application for removal of phenol in aqueous solution through adsorption process. Two types of activation namely; thermal activation at 300, 500 and 800 degrees C and physical activation at 150 degrees C (boiling treatment) were used for the production of the activated carbons. A control (untreated EFB) was used to compare the adsorption capacity of the activated carbons produced from these processes. The results indicated that the activated carbon derived at the temperature of 800 degrees C showed maximum absorption capacity in the aqueous solution of phenol. Batch adsorption studies showed an equilibrium time of 6 h for the activated carbon at 800 degrees C. It was observed that the adsorption capacity was higher at lower values of pH (2-3) and higher value of initial concentration of phenol (200-300 mg/L). The equilibrium data fitted better with the Freundlich adsorption isotherm compared to the Langmuir. Kinetic studies of phenol adsorption onto activated carbons were also studied to evaluate the adsorption rate. The estimated cost for production of activated carbon from EFB was shown in lower price (USD 0.50/kg of activated carbon) compared the activated carbon from other sources and processes. PMID:17913162

  17. Synthesis and evaluation of antimicrobial activity of novel 1,3,4-oxadiazole derivatives

    Popat B. Mohite

    2011-09-01

    Full Text Available In attempt to find new pharmacologically active molecules, we report here the synthesis and in vitro antimicrobial activities of various novel 1,3,4-oxadiazole containing 5-phenyltetrazole. The Schiff bases were obtained by condensation 2-(5-phenyl-1H-tetrazol-1-ylacetohydrazide with various aromatic aldehydes. Cyclocondensation of Schiff’s bases with acetic anhydride results in 1,3,4-oxadiazole derivatives. The structures of the newly synthesized 1,3,4-oxadiazole were confirmed by FT-IR, 1H NMR and mass spectral data. The antimicrobial activity was determined by MIC method. All the compounds exhibited weak to potent antimicrobial activity. Some derivatives bearing a methoxy group exhibited very good antimicrobial activity at conc. of 62.5 µg/mL.

  18. Synthesis, Anti-Inflammatory and Anti-oxidant activity of some substituted Benzimidazole Derivatives

    Rajasekaran S

    2012-09-01

    Full Text Available Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-fungal, antitumor and anthelmintic activity. In addition, few N-substituted benzimidazole derivatives have shown to exhibit significant activity against several viruses, including HIV, herpes simplex (HSV-1, influenza, picorna, human cytomegalovirus (HCMV and hepatitis C virus. The five membered heterocyclic moiety 1,3,4-oxadiazole also confers for various biological activity. Hence a series of benzimidazole derivatives fused with oxadiazole ring system have been synthesized, characterized by UV, IR and 1H NMR spectral data and evaluated for their in vitro and in vivo anti-inflammatory and antioxidant activity.

  19. In vitro Potentiation of Antimalarial Activities by Daphnetin Derivatives Against Plasmodium falciparum

    FANG HUANG; LIN-HUA TANG; LIN-QIAN YU; YI-CHANG NI; QIN-MEI WANG; FA-JUN NAN

    2006-01-01

    Objective To screen the antimalarial compounds of daphnetin derivatives against Plasmodium falciparum in vitro. Method Plasmodium faciparum (FCC1) was cultured in vitro by a modified method of Trager and Jensen. Antimalarial compounds were screened by microscopy-based assay and microfluorimetric method. Results DA79 and DA78 showed potent antimalarial activity against Plasmodium falciparum cultured in vitro. Conclusion Though the relationship between the structures of daphnetin derivatives and their antimalarial activities has not been clarified yet, this study may provide a new direction for discovery of more potential antimalarial compounds.

  20. New stereoselective titanium reductive amination synthesis of 3-amino and polyaminosterol derivatives possessing antimicrobial activities.

    Salmi, Chanaz; Loncle, Celine; Vidal, Nicolas; Letourneux, Yves; Brunel, Jean Michel

    2008-03-01

    A series of 3-amino and polyaminosterol analogues of squalamine and trodusquemine were synthesized involving a new stereoselective titanium reductive amination reaction in high chemical yields of up to 95% in numerous cases. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. Activity was highly dependent on the different compounds' structures involved and best results have been obtained with aminosterol derivatives 4b, 4e and 6i exhibiting activities against yeasts, Gram positive and Gram negative bacteria at average concentrations of 6.25-12.5 microg/mL. PMID:17566609

  1. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives

    Gaballah, Samir T.; El-Nezhawy, Ahmed O. H.; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas

    2015-01-01

    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a–i) and sulfoxide (5a–h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a–i) and sulfoxide (5a–h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presen...

  2. SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME CHALCONE DERIVATIVES AND THEIR COPPERCOMPLEXES

    P. M. Rachmale

    2012-03-01

    Full Text Available In the present investigation, 4-chloro acetophenone on condensation with 2-nitro benzaldehydes in methanolic NaOH solution yielded the corresponding chalcone. These chalcone were further reacted with Isonicotyl hydrazide and semicarbazide in ethanol which led to the formation of chalcone Isonicotyl hydrazone and chalcone semicarbazone derivatives respectively. The newly synthesized derivatives and there copper complexes were characterized on the basis of their chemical properties and spectroscopic data such as IR, NMR and UV. All newly synthesized compounds were evaluated for their antibacterial activities against E. coli and S. aureus also for antifungal activities against P. notatum.

  3. Synthesis, Cytotoxic Activity and 2D-QSAR Study of Some Imidazoquinazoline Derivatives

    Hanan Georgey

    2014-03-01

    Full Text Available A novel series of 4-substituted amino-7,8-dimethoxy-1-phenylimidazo[1,5-a]quinazolin-5(4H-one derivatives was designed, synthesized and tested for their antitumor activity against a human mammary carcinoma cell line (MCF7. Compound 5a was found to be the most active derivative. Physico-chemical parameters were also determined and revealed that most of the compounds obeyed the “rule of five” properties with good absorption percentages. 2D-QSAR studies revealed a well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.

  4. Activated carbons derived from oil palm empty-fruit bunches: Application to environmental problems

    Md.Zahangir ALAM; Suleyman A.MUYIBI; Mariatul F.MANSOR; Radziah WAHID

    2007-01-01

    Activated carbons derived from oil palm empty fruit bunches (EFB) were investigated to find the suitability of its application for removal of phenol in aqueous solution through adsorption process. Two types of activation namely; thermal activation at 300, 500 and 800℃ and physical activation at 150℃ (boiling treatment) were used for the production of the activated carbons. A control (untreated EFB) was used to compare the adsorption capacity of the activated carbons produced from these processes. The results indicated that the activated carbon derived at the temperature of 800℃ showed maximum absorption capacity in the aqueous solution of phenol. Batch adsorption studies showed an equilibrium time of 6 h for the activated carbon at 800℃. It was observed that the adsorption capacity was higher at lower values of pH (2-3) and higher value of initial concentration of phenol (200-300 mg/L). The equilibrium data fitted better with the Freundlich adsorption isotherm compared to the Langmuir. Kinetic studies of phenol adsorption onto activated carbons were also studied to evaluate the adsorption rate. The estimated cost for production of activated carbon from EFB was shown in lower price (USD 0.50/kg of AC) compared the activated carbon from other sources and processes.

  5. Synthesis and Biological Activity of Peptide Derivatives of Iodoquinazolinones/Nitroimidazoles

    Rakesh Yadav

    2008-04-01

    Full Text Available Two substituted quinazolinyl/imidazolyl-salicylic acids 5, 6 were synthesized bythe reaction of 6-iodo-2-methylbenzoxazin-4-one/5-nitroimidazole with 5-aminosalicylicacid (5-ASA. Coupling of compounds 5 and 6 with different amino acid esterhydrochlorides, dipeptide and tripeptide methyl esters yielded novelquinazolino/imidazolopeptide derivatives 5a-f and 6a-g. The chemical structures of allnewly synthesized compounds were confirmed by means of FT-IR, 1H- and 13C-NMR, MSand elemental analysis. Selected peptide ester derivatives were further hydrolyzed by usinglithium hydroxide (LiOH to afford the corresponding acid derivatives 5ba-da and 6ea-ga.All peptide derivatives were assayed for antimicrobial and anthelmintic activities againsteight pathogenic microbes and three earthworm species. Among the tested compounds, 5e,5d, 6e and their hydrolyzed analogs 5da and 6ea exhibited higher antimicrobial activityagainst Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and 5a,6g and 6ga displayed better antifungal activity against the dermatophytes Trichophytonmentagrophytes and Microsporum audouinii. Moreover, 6f and its hydrolyzed derivative6fa showed good anthelmintic activity against Megascoplex konkanensis, Pontoscotexcorethruses and Eudrilus eugeniea at dose of 2 mg mL–1.

  6. Complete assignments of NMR data and assessment of trypanocidal activity of new eremantholide C derivatives

    Saude-Guimaraes, Denia Antunes, E-mail: saude@ef.ufop.br, E-mail: saudeguima@gmail.com [Universidade Federal de Ouro Preto (UFOP), MG (Brazil); Raslan, Delio S.; Chiari, Egler; Oliveira, Alaide B. de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2014-12-15

    Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1’,2’- epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1’,2’-epoxyeremantholide C (3), 5-n-propylammonium-4,5-dihydro-1’,2’-epoxyeremantholide C chloride (4), 5-n-propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide C (6). The structures of all these derivatives were assigned on the basis of IR, MS, {sup 1}H and {sup 13}C NMR data by 1D and 2D techniques. Eremantholide C and the derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the parasites strains while all derivatives were partially active against the CL strain and inactive against the Y strain. (author)

  7. Lipid Peroxidation Inhibitation Activity of Maillard Reaction Products Derived from Sugar-amino Acid Model Systems

    Nanjing Zhong

    2015-08-01

    Full Text Available The present study aimed to evaluate the lipid peroxidation inhibitation activity of Maillard Reaction Products (MRPs derived from sugar (glucose, fructose, lactose and maltose and 18 amino acid model systems in soybean oil. MRPs were produced by heating at 130°C for 2 h. Of the 18 amino acids-fructose model systems studied, MRPs derived from fructose-leucine, fructose-methionine, fructose-phenylalanine and fructose-isoleucine model sytems showed high lipid peroxidation inhibitation activity and best performance was observed from fructose-phenylalanine MRPs. Interestingly, glucose-phenylalanine MRPs also exhibited high inhibitation activity and inhibitation activity of both glucose-phenylalanine and fructose-phenylalanine MRPs exceeded 87% even with concentration at 1.1 wt % after 8 days storage.

  8. In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of a Novel Nitro-derivative

    Susana Muelas-Serrano

    2002-06-01

    Full Text Available Nitroarylidenemalononitriles and their cyanoacetamide derivatives with remarkable anti-epimastigote properties, were synthesized attempting to obtain new 3,5-diamino-4-(5'-nitroarylidene-4H-thiadiazine 1,1-dioxide derivatives, which in previous reports had shown anti-Trypanosoma cruzi activity. Tests to evaluate the cytotoxicity of compounds were performed on J774 macrophages. 5-nitro-2-thienyl-malononitrile (5NO2TM, was the only product which maintained a high anti-epimastigote activity at concentrations in which it was no longer cytotoxic, thus it was assayed against intracellular amastigotes. Its anti-amastigote activity was similar to that of nifurtimox. Afterwards in vivo toxicity and anti-chagasic activity were determined. A reduction in parasitemia was observed.

  9. Antibacterial, antifungal and antimycobacterial activities of some pyrazoline, hydrazone and chalcone derivatives.

    Evranos-Aksöz, Begüm; Onurdağ, Fatma Kaynak; Özgacar, Selda Özgen

    2015-07-01

    Twenty-seven previously reported chalcones and their pyrazoline and hydrazone derivatives as well as two further chalcones have been screened for their antimicrobial, antifungal and antimycobacterial activities against standard microbial strains and drug resistant isolates. The minimum inhibitory concentration (MIC) value of each compound was determined by a two-fold serial microdilution technique. The compounds were found to possess a broad spectrum of antimicrobial activities with MIC values of 8-128 μg/mL. One compound [(E)-1-(4-hydroxyphenyl)-3-p-tolylprop-2-en-1-one] had equal activity with gentamycin (8 μg/mL) against Enterococcus faecalis. Chalcones were found to be more active than their hydrazone and 2-pyrazoline derivatives against Staphylococcus aureus ATCC 29213 and E. faecalis ATCC 29212. PMID:26372110

  10. A chemometric approach for prediction of antifungal activity of some benzoxazole derivatives against Candida albicans

    Podunavac-Kuzmanović Sanja O.

    2012-01-01

    Full Text Available The purpose of the article is to promote and facilitate prediction of antifungal activity of the investigated series of benzoxazoles against Candida albicans. The clinical importance of this investigation is to simplify design of new antifungal agents against the fungi which can cause serious illnesses in humans. Quantitative structure activity relationship analysis was applied on nineteen benzoxazole derivatives. A multiple linear regression (MLR procedure was used to model the relationships between the molecular descriptors and the antifungal activity of benzoxazole derivatives. Two mathematical models have been developed as a calibration models for predicting the inhibitory activity of this class of compounds against Candida albicans. The quality of the models was validated by the leave-one-out technique, as well as by the calculation of statistical parameters for the established model. [Projekat Ministarstva nauke Republike Srbije, br. 172012 i br. 172014

  11. Halogenated benzoate derivatives of altholactone with improved anti-fungal activity.

    Euanorasetr, Jirayut; Junhom, Mayura; Tantimavanich, Srisurang; Vorasin, Onanong; Munyoo, Bamroong; Tuchinda, Patoomratana; Panbangred, Watanalai

    2016-05-01

    Altholactone exhibited the anti-fungal activity with a high MIC value of 128 μg ml(-1) against Cryptococcus neoformans and Saccharomyces cerevisiae. Fifteen ester derivatives of altholactone 1-15 were modified by esterification and their structures were confirmed by spectroscopic methods. Most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-Bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentration (MIC) values against C. neoformans at 16 μg ml(-1), while the 4-bromo-, 4-iodo-, and 1-bromo-3-chlorobenzoates (11-13) displayed potent activity against S. cerevisiae with MIC values of 1 μg ml(-1). In conclusion, this analysis indicates that the anti-fungal activity of altholactone is enhanced by addition of halogenated benzoyl group to the 3-OH group. PMID:26765144

  12. 5α-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives.

    Al-Mohizea, Abdullah M; Al-Omar, Mohamed A; Abdalla, Mohamed M; Amr, Abdel-Galil E

    2012-01-01

    We herein report the 5α-reductase inhibitors, antiviral and anti-tumor activities of some synthesized heterocyclic cyanopyridone and cyanothiopyridone derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds, except 3b, were interestingly less toxic than the reference drug (Prednisolone(®)). Seventeen heterocyclic derivatives containing a cyanopyridone or cyanothiopyridone rings fused to a steroidal moiety were synthesized and screened for their 5α-reductase inhibitors, antiviral and anti-tumor activities comparable to that of Anastrozole, Bicalutamide, Efavirenz, Capravirine, Ribavirin, Oseltamivir and Amantadine as the reference drugs. Some of the compounds exhibited better 5α-reductase inhibitors, antiviral and anti-tumor activities than the reference drugs. The detailed 5α-reductase inhibitors, antiviral and anti-tumor activities of the synthesized compounds were reported. PMID:22057085

  13. Synthesis of 4-Amino-1,5-dimethyl-2-phenylpyrazolone Derivatives and their Antioxidant Activity

    Schiff bases of 4-amino-1,5-dimethyl-2-phenylpyrazolone (2-18) were synthesized by treating with different benzaldehyde derivatives and tested for in vitro antioxidant activity. Synthesized Schiff base derivatives (2-18) were characterized by various spectroscopic techniques. Compounds specially having hydroxyl substituents showed good DPPH radical scavenging activity having IC/sub 50/ values between 15.16 and 48.26 meu M. Compounds 3-7 showed stronger potency than the standard (n-propyl gallate, IC/sub 50/ = 30.27 ± 0.25 meu M). However, in the superoxide anion radical assay, derivatives 2, 4, 5, 6 and 7 showed better potency than the standard (n-propyl gallate, IC/sub 50/ = 106.34 ± 1.60 meu M). (author)

  14. Antioxidant activity of galloyl quinic derivatives isolated from P. lentiscus leaves.

    Baratto, Maria Camilla; Tattini, Massimiliano; Galardi, Carlotta; Pinelli, Patrizia; Romani, Annalisa; Visioli, Francesco; Basosi, Riccardo; Pogni, Rebecca

    2003-04-01

    The antioxidant properties of galloyl quinic derivatives isolated from Pistacia lentiscus L. leaves have been investigated by means of Electron Paramagnetic Resonance spectroscopy (EPR) and UV-Vis spectrophotometry. Antioxidant properties have been also estimated using the biologically relevant LDL test. The scavenger activities of gallic acid, 5-O-galloyl, 3,5-O-digalloyl, 3,4,5-O-trigalloyl quinic acid derivatives, have been estimated against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide (O2) radical, and hydroxyl (OH) radical. On the whole, the scavenger activity raised as the number of galloyl groups on the quinic acid skeleton increased. The half-inhibition concentrations (IC50) of di- and tri-galloyl derivatives did not exceed 30 microM for all the tested free radicals. All the tested metabolites strongly reduced the oxidation of low-density lipoproteins (LDL), following a trend similar to that observed for the scavenger ability against OH radical. PMID:12747734

  15. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

    Bobek Libuse A; Campagna Alexander N; Wei Guo-Xian

    2007-01-01

    Abstract Background MUC7 12-mer (RKSYKCLHKRCR), a cationic antimicrobial peptide derived from the human low-molecular-weight salivary mucin MUC7, possesses potent antimicrobial activity in vitro. In order to evaluate the potential therapeutic application of the MUC7 12-mer, we examined the effects of mono- and divalent cations, EDTA, pH, and temperature on its antimicrobial activity. Methods Minimal Inhibitory Concentrations (MICs) were determined using a liquid growth inhibition assay in 96-...

  16. Antimicrobial Activity of Chitosan Derivatives Containing N-Quaternized Moieties in Its Backbone: A Review

    Alessandro F. Martins; Suelen P. Facchi; Follmann, Heveline D. M.; Antonio G. B. Pereira; Adley F. Rubira; Muniz, Edvani C.

    2014-01-01

    Chitosan, which is derived from a deacetylation reaction of chitin, has attractive antimicrobial activity. However, chitosan applications as a biocide are only effective in acidic medium due to its low solubility in neutral and basic conditions. Also, the positive charges carried by the protonated amine groups of chitosan (in acidic conditions) that are the driving force for its solubilization are also associated with its antimicrobial activity. Therefore, chemical modifications of chitosan ...

  17. Mechanism of anti-influenza virus activity of Maillard reaction products derived from Isatidis roots

    Ke, Lijing

    2011-01-01

    The cyto-protective compositions and effects of antiviral Maillard reaction products (MRPs) derived from roots of Isatis indigotica F. were examined using biochemical and biophysical methods. The Maillard reaction was identified as the main source of compounds with antiviral activity, an observation which has led to the proposal of a new class of active compounds that protect cells from influenza virus infection. In the roots, arginine and glucose were revealed to be the predom...

  18. Design, synthesis and antitumor activity of 3-substituted quinolone derivatives (Ⅰ)

    2008-01-01

    A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor cells are comparable to that of topotecan, one of topoisomerase I inhibitors.

  19. A new class of multi-substituted oxazole derivatives: Synthesis and antimicrobial activity

    A Babul Reddy; R V Hymavathi; G Narayana Swamy

    2013-05-01

    A new and efficient method for the synthesis of multi-substituted oxazole derivatives from various aldehydes has been described. Twenty novel multi-substituted oxazoles containing a heterocyclic moiety were synthesized and evaluated for their antimicrobial activity. The prepared compounds are all reported for the first time and their structures were established by elemental analysis, IR, 1H-NMR, and 13C-NMR and Mass spectra. All the synthesized compounds exhibited in vitro antimicrobial activity.

  20. RECENT ADVANCES OF QUINAZOLINONE DERIVATIVES AS MARKER FOR VARIOUS BIOLOGICAL ACTIVITIES

    Anshul Chawla; Chesta Batra

    2013-01-01

    Heterocyclic chemistry comprises at least half of all organic chemistry research worldwide. Quinazolinone and its derivatives constitute an important class of heterocyclic compounds. The chemistry of quinazoline compounds has more than centuries old history; however the intense search for biologically active substances in this series began only in the last few decades. In this present communication an attempt is made to cover the medicinally active compounds, along with the recent discoveries...

  1. Estimation of muscle activity using higher-order derivatives, static optimization, and forward-inverse dynamics.

    Yamasaki, Taiga; Idehara, Katsutoshi; Xin, Xin

    2016-07-01

    We propose a new method to estimate muscle activity in a straightforward manner with high accuracy and relatively small computational costs by using the external input of the joint angle and its first to fourth derivatives with respect to time. The method solves the inverse dynamics problem of the skeletal system, the forward dynamics problem of the muscular system, and the load-sharing problem of muscles as a static optimization of neural excitation signals. The external input including the higher-order derivatives is required for a calculation of constraints imposed on the load-sharing problem. The feasibility of the method is demonstrated by the simulation of a simple musculoskeletal model with a single joint. Moreover, the influences of the muscular dynamics, and the higher-order derivatives on the estimation of the muscle activity are demonstrated, showing the results when the time constants of the activation dynamics are very small, and the third and fourth derivatives of the external input are ignored, respectively. It is concluded that the method can have the potential to improve estimation accuracy of muscle activity of highly dynamic motions. PMID:27211782

  2. Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities

    Aissa Imen

    2012-01-01

    Full Text Available Abstract Background Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants. Results A large series of tyrosyl esters (TyC2 to TyC18:1 with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435. Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. Conclusion These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries.

  3. Probing the Active Surface Sites for CO Reduction on Oxide-Derived Copper Electrocatalysts

    Verdaguer Casadevall, Arnau; Li, Christina W.; Johansson, Tobias Peter; Scott, Soren B.; McKeown, Joseph T.; Kumar, Mukul; Stephens, Ifan E. L.; Kanan, Matthew W.; Chorkendorff, Ib

    2015-01-01

    CO electroreduction activity on oxide-derived Cu (OD-Cu) was found to correlate with metastable surface features that bind CO strongly. OD-Cu electrodes prepared by H-2 reduction of Cu2O precursors reduce CO to acetate and ethanol with nearly 50% Faradaic efficiency at moderate overpotential. Tem...

  4. Activated anilide in heterocyclic synthesis: Synthesis of new hydrazo, dihydropyridazine, tetrahydropyridine, dihydropyridine and pyranopyridine derivatives

    Ibrahim Saad Abdel Hafiz; Mahmoud Mohamed Mahfouz Ramiz; Mohamed Ahmed Elian

    2012-05-01

    A series of new hydrazo, dihydropyridazine, tetrahydropyridine, dihydropyridine and pyranopyridine derivatives with known biological activity have been prepared through the reactions of 3-oxo-3-phenyl-N- (pyridine-3-yl) propanamide 3 and enaminonitrile 17 with some electrophilic reagents, nucleophilic reagents, and aryl diazonium salts. The newly synthesized compounds were characterized by IR, 1H NMR and mass spectral studies.

  5. Quantitative structure activity relationship study of anticonvulsant activity of α_substituted acetamido-N-benzylacetamide derivatives

    Usman Abdulfatai

    2016-12-01

    Full Text Available To develop the quantitative structure–activity relationship (QSAR for predicting the anticonvulsant activity of α_substituted acetamido-N-benzylacetamide derivatives. Density Functional Theory (B3LYP/6-31G* quantum chemical calculation method was used to find the optimized geometry of the studied molecules. Nine types of molecular descriptors were used to derive a quantitative relation between anticonvulsant activity and structural properties. The relevant molecular descriptors were selected by genetic algorithm approximation. The high value of the correlation coefficient, (R2 of 0.98, indicates that the model was satisfactory. The proposed model has good stability, robustness, and predictability on verifying with internal and external validation.

  6. Effects of thermal activation conditions on the microstructure regulation of corncob-derived activated carbon for hydrogen storage

    Dabin Wang; Zhen Geng; Cunman Zhang; Xiangyang Zhou; Xupeng Liu

    2014-01-01

    Activated carbons derived from corncob (CACs) were prepared by pyrolysis carbonization and KOH activation. Through modifying activation conditions, samples with large pore volume and ultrahigh BET specific surface area could be obtained. The sample achieved the highest hydrogen uptake capacity of 5.80 wt%at 40 bar and -196◦C. The as-obtained samples were characterized by N2-sorption, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Besides, thermogravimetric analysis was also employed to investigate the activation behavior of CACs. Detailed investigation on the activation parameters reveals that moderate activation temperature and heating rate are favorable for preparing CACs with high surface area, large pore volume and optimal pore size distribution. Meanwhile, the micropore volume between 0.65 nm and 0.85 nm along with BET surface area and total pore volume has great effects on hydrogen uptake capacities. The present results indicate that CACs are the most promising materials for hydrogen storage application.

  7. Lycibarbarspermidines A-O, New Dicaffeoylspermidine Derivatives from Wolfberry, with Activities against Alzheimer's Disease and Oxidation.

    Zhou, Zheng-Qun; Fan, Hong-Xia; He, Rong-Rong; Xiao, Jia; Tsoi, Bun; Lan, Kang-Hua; Kurihara, Hiroshi; So, Kwok-Fai; Yao, Xin-Sheng; Gao, Hao

    2016-03-23

    Fifteen new dicaffeoylspermidine derivatives, lycibarbarspermidines A-O (1-15), were isolated from the fruit of Lycium barbarum (wolfberry). The structures were unambiguously determined by spectroscopic analyses and chemical methods. Dicaffeoylspermidine derivatives, a rare kind of plant secondary metabolites, are primarily distributed in the family of Solanaceae. Only six compounds were structurally identified, and all of them are acyclic aglycones. Compounds 1-15 are the first glycosidic products of dicaffeoylspermidine derivatives, and compounds 14-15 are the first cyclization products of dicaffeoylspermidine derivatives. Moreover, dicaffeoylspermidine derivatives were first isolated and identified from wolfberry. The short-term memory assay on a transgenic fly Alzheimer's disease (AD) model showed that 1-15 exhibited different levels of anti-AD activity. The oxygen radical absorbance capacity assay revealed that 1-15 all displayed antioxidant capacity. Both anti-AD and antioxidant functions are related to the effects of wolfberry. Therefore, dicaffeoylspermidine derivatives are considered beneficial constituents responsible for the antiaging, neuroprotective, anti-AD, and antioxidant effects of wolfberry. PMID:26953624

  8. Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents.

    Liu, Cong-Jun; Yu, Shu-Ling; Liu, Yan-Ping; Dai, Xing-Jie; Wu, Ya; Li, Rui-Jun; Tao, Jing-Chao

    2016-06-10

    A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 μM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule. PMID:26994841

  9. Design, synthesis and structure-activity relationship of novel diphenylamine derivatives.

    Li, Huichao; Guan, Aiying; Huang, Guang; Liu, Chang-Ling; Li, Zhinian; Xie, Yong; Lan, Jie

    2016-02-01

    Diphenylamine derivatives have been reported with good fungicidal, insecticidal, acaricidal, rodenticidal and/or herbicidal activities. To find new lead compound of this kind, a series of novel diphenylamine derivatives were designed and synthesized by the approach of Intermediate Derivatization Methods. All compounds were identified by (1)H NMR and elemental analysis. Bioassays demonstrated that some compounds substituted at 2,4,6-positions or 2,4,5-positions of phenyl ring B exhibited excellent fungicidal activities. The optimal compounds P30 and P33 showed 80% and 85% control respectively against cucumber downy mildew at 12.5mgL(-1), both 100% control against rice blast at 0.3mgL(-1) and both 100% control against cucumber gray mold at 0.9mgL(-1). The relationship between structure and fungicidal activities was discussed as well. PMID:26432603

  10. Synthesis and Antimicrobial Activity of 4-Chloro-3-Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases.

    Bielenica, Anna; Stępień, Karolina; Napiórkowska, Agnieszka; Augustynowicz-Kopeć, Ewa; Krukowski, Sylwester; Włodarczyk, Marta; Struga, Marta

    2016-06-01

    A series of novel 4-chloro-3-nitrophenylthiourea derivatives were synthesized and evaluated for their antimicrobial, antibiofilm and tuberculostatic activities. Most of compounds exhibited high antibacterial activity against both standard and hospital strains (MIC values 0.5-2 μg/mL), as compared to Ciprofloxacin. Derivatives with 3,4-dichlorophenyl (11) and 3-chloro-4-methylphenyl (13) substituents were the most promising towards Gram-positive pathogens. Both of them exhibited antibiofilm potency and effectively inhibited the formation of biofilms of methicillin-resistant and standard strains of Staphylococcus epidermidis. Two N-alkylthioureas (20, 21) showed twofold to fourfold increase in in vitro potency against isolates of Mycobacterium tuberculosis, as compared to Isoniazid. An action of 7, 10, 11, 13, 20 and 21 against activity of topoisomerases isolated from Staphylococcus aureus was studied. Synthesized compounds were found as non-genotoxic. PMID:26804238

  11. New pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity.

    Carvalho, Rita C C; Martins, Wagner A; Silva, Tayara P; Kaiser, Carlos R; Bastos, Mônica M; Pinheiro, Luiz C S; Krettli, Antoniana U; Boechat, Núbia

    2016-04-15

    Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)n=2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n=4 and 7-chloroquinolinyl has displayed better activity (IC50=0.40μM) than chloroquine. The primaquine derivative showed IC50=1.41μM, being less toxic and more active than primaquine. PMID:26988303

  12. Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

    Liu, X.-F. [Huazhong Univ. of Science and Technology, Dept. of Chemistry, Wuhan (China); Hubei Univ., Ministry of Education Key Lab. for the Synthesis and Application of Organic Functional Molecules, Wuhan (China); Guan, W.-C. [Huazhong Univ. of Science and Technology, Dept. of Chemistry, Wuhan (China)], E-mail: wcguan04@yahoo.com.cn; Ke, W.-S. [Hubei Univ., College of Life Science, Wuhan (China)

    2007-03-15

    A C{sub 60}-based ebselen derivative 4 was synthesized through the cycloaddition of C{sub 60} with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C{sub 60}). Its structure was characterized by {sup 1}H NMR, {sup 13}C NMR, IR, UV, and FAB-MS. To verify that the C{sub 60}-based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C{sub 60} derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C{sub 60}-based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 {mu}mol/L), the results showed that the antioxidative and protective potencies of the C{sub 60}-based ebselen derivative 4 (MTT (OD) 0.340 {+-} 0.035, LDH release (UL{sup -1}) 4.80 {+-} 0.16) against H{sub 2}O{sub 2}-mediated neuronal injury have an advantage over those of C{sub 60} derivative 5 (MTT (OD) 0.297 {+-} 0.036, LDH release (UL{sup -1}) 5.37 {+-} 0.31) and ebselen derivative 6 (MTT (OD) 0.267 {+-} 0.027, LDH release (UL{sup -1}) 5.85 {+-} 0.26). Correspondingly, the GPX activity of 4 (1.62 U/{mu}mol) was higher than that of 5 (0.77 U/{mu}mol) and 6 (1.24 U/{mu}mol). These findings demonstrate that the incorporation of two components with similar biological activity (C{sub 60} component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C{sub 60}-based compound. (author)

  13. Inhibition of M-MuLV reverse transcriptase activity by fullerene derivatives

    MENG Xianmei; CHEN Zhe; LI Bo; ZHANG Yufei; ZHAO Dongxu; YANG Xinlin

    2006-01-01

    Influence of fullerene (C6o) derivatives on M-MuLV reverse transcriptase activity is investigated. Two water-soluble fullerene derivatives, fullerol (C60(OH)23-24) and trimalonic acid C60 (TMA C60,C63(COOH)6) are used in the experiments and their effects on in vitro reverse transcription-polymerase chain reaction (RT-PCR) of β-actin mRNA in HeLa cells are determined. PCR products are detected by agarose gel electrophoresis. It is found that the amounts of PCR products decrease with addition of either of two fullerene derivatives to RT reaction mixture. The inhibition of fullerene derivatives is dose-dependent, and IC50 values of fullerol and TMA C60 are 0.089 and 0.039 mmol/L, respectively. The amount of PCR products obtained by direct addition of fullerol or TMA C60 to PCR are greater than those obtained by addition of the equivalent amount of fullerol or TMA C60 to RT, indicating an inhibitory effect of fullerol or TMA C60 on RT. The compensative experiment of M-MuLV reverse transcriptase shows that increasing enzyme amounts can antagonize the activity of fullerol or TMA C60. These results imply that fullerenes can inhibit M-MuLV reverse transcriptase activity, with the inhibition of TMA C60 slightly stronger than fullerol, and that their potential in treatment of diseases induced by RNA viruses such as leukemia virus needs further investigation.

  14. Synthesis and antifungal activity evaluation of new heterocycle containing amide derivatives.

    Wang, Xuesong; Gao, Sumei; Yang, Jian; Gao, Yang; Wang, Ling; Tang, Xiaorong

    2016-01-01

    A series of heterocycle containing amide derivatives (1-28) were synthesised by the combination of acyl chlorides (1a, 2a) and heterocyclic/homocyclic ring containing amines, and their in vitro antifungal activity was evaluated against five plant pathogenic fungi, namely Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum. Results of antifungal activity analysis indicated that some of the products showed good to excellent antifungal activity, as compound 2 showed excellent activity against G. zeae and R. solani and potent activity against H. maydi, B. cinerea and S. sclerotiorum, and compounds 1, 8 and 10 also displayed excellent antifungal potential against H. maydi, B. cinerea and S. sclerotiorum and good activity against R. solani when compared with the standard carbendazim. PMID:26140452

  15. Synthesis of Hydroxystilbene Derivatives and their Antioxidant Activity by DPPH Method

    2006-01-01

    Five hydroxystilbene derivatives were synthesized and their structures were determined using high-resolution mass spectrometry, 1H NMR, and IR. In this study, the antioxidant activities of eight hydroxystilbenes(five synthesized hydroxystilbene derivatives and three other compounds) were evaluated with the free radical scavenging model 1,1-diphenyl-2-picrylhydrazyl. It was observed that there exists a very significant linear relationship between the reciprocal of the EC50 value of each of the compounds and the maximum wavelength of the ultraviolet absorption peaks. It is believed that this result will be helpful for the further synthesis of such antioxidants.

  16. Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity

    Krzysztof M. Borys

    2012-02-01

    Full Text Available A halogenmethylsulfonyl moiety is incorporated in numerous active herbicides and fungicides. The synthesis of tribromomethyl phenyl sulfone derivatives as novel potential pesticides is reported. The title sulfone was obtained by following three different synthetic routes, starting from 4-chlorothiophenol or 4-halogenphenyl methyl sulfone. Products of its subsequent nitration were subjected to the SNAr reactions with ammonia, amines, hydrazines and phenolates to give 2-nitroaniline, 2-nitrophenylhydrazine and diphenyl ether derivatives. Reduction of the nitro group of 4-tribromomethylsulfonyl-2-nitroaniline yielded the corresponding o-phenylenediamine substrate for preparation of structurally varied benzimidazoles.

  17. Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.

    Wu, Yuelin; Min, Xiao; Zhuang, Chunlin; Li, Jin; Yu, Zhiliang; Dong, Guoqiang; Yao, Jiangzhong; Wang, Shengzheng; Liu, Yang; Wu, Shanchao; Zhu, Shiping; Sheng, Chunquan; Wei, Yunyang; Zhang, Huojun; Zhang, Wannian; Miao, Zhenyuan

    2014-07-23

    In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity. PMID:24937186

  18. Synthesis and Biological Activity of Arylspiroborate Salts Derived from Caffeic Acid Phenethyl Ester

    Martin J. G. Hébert

    2015-01-01

    Full Text Available Two novel boron compounds containing caffeic acid phenethyl ester (CAPE derivatives have been prepared and characterized fully. These new compounds and CAPE have been investigated for potential antioxidant and antimicrobial properties and their ability to inhibit 5-lipoxygenase and whether chelation to boron improves their biological activity. Sodium salt 4 was generally more active than ammonium salt 5 in the biological assays and surpassed the radical scavenging ability of CAPE. Compounds 4 and 5 were more active than CAPE and Zileuton in human polymorphonuclear leukocytes. These results clearly show the effectiveness of the synthesized salts as transporter of CAPE.

  19. Synthesis and antiproliferative activity of novel limonene derivatives with a substituted thiourea moiety

    A series of R-(+)-limonene derivatives bearing a substituted thiourea moiety (3-13) and five S-methyl analogs (14-18) were synthesized and evaluated for their in vitro antiproliferative activity against human cancer cell lines. Compounds bearing aromatic substituents (3-6) exhibit cytostatic activity in the full panel of cell lines tested, with GI50 values in the range of 2.5 to 24 μmol L-1. Compounds 3, 10, 12 and 16 were the most active with GI5)0 values in the range of 0.41 to 3.0 μmol L-1, against different cell lines. (author)

  20. Synthesis and Anticonvulsant Activity of Some Quinazolin-4-(3H-one Derivatives

    Safinaz Abbas

    2008-10-01

    Full Text Available A number of 3-substituted-2-(substituted-phenoxymethyl quinazolin-4(3H-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS. A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds 6, 8b and 8d show mild to moderate activity.

  1. Design, synthesis and antiproliferative activities of diaryl urea derivatives bearing N-acylhydrazone moiety

    Bei Zhang; Yan Fang Zhao; Xin Zhai; Wei Jie Fan; Jun Ling Ren; Chun Fu Wu; Ping Gong

    2012-01-01

    A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized.All the target compounds were evaluated for their antiproliferative activities against human leukemia cell line (HL-60),human lung adenocarcinoma epithelial cell hne (A549) and human breast cancer cell line (MDA-MB-231) in vitro by standard MTT assay.The pharmacological results indicated that some compounds exhibited promising antitumor activities.Compound lj showed the most potent antiproliferative activity against the tested three cell lines with IC50 values of 0.13 μmol/L,0.7 μ mol/L and 0.5 μmol/L,respectively.

  2. Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D derivatives.

    Chen, Zhong; Duan, Huaqing; Wang, Minglei; Han, Li; Liu, Yanli; Zhu, Yongming; Yang, Shilin

    2015-06-15

    The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated. Structure-activity relationship and structure-toxicity relationship had been observed. The mice acute toxicity of compound 11 was reduced greatly than that of PSA. This study indicates that compound 11 may represent an interesting class of potent antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The present study has important significance for the development of antitumor saponins. PMID:25958248

  3. Synthesis, anti-microbial activity and molecular docking studies on triazolylcoumarin derivatives

    Chinnadurai Satheeshkumar; Mahalingam Ravivarma; Pandian Arjun; Vaithiyanathan Silambarasan; Nanjian Raaman; Devadasan Velmurugan; Changsik Song; Perumal Rajakumar

    2015-03-01

    A series of triazolylcoumarins was synthesized by the cycloaddition of acetylenic derivatives to azide in the presence of Cu(I) catalyst at room temperature. All the synthesized compounds were evaluated for their anti-microbial activity against Gram-positive (B. subtilis and S. aureus), Gram-negative bacteria (K. pneumonia and P. vulgaris) and human pathogenic fungi (C. tropicalis and C. krusei), with tetracycline and fluconazole as standards for anti-microbial and anti-fungal activity. Triazolylcoumarins exhibit anti-microbial activity against all the tested pathogens, which is further supported by molecular docking studies.

  4. Microwave-assisted synthesis, characterization and biological activity of novel pyrazole derivatives

    Theivendren Panneer Selvam

    2014-12-01

    Full Text Available A series of 1-(4-substitutedphenyl-3-phenyl-1H-pyrazole-4-carbaldehydes 4a–l have been synthesized and tested for their biological activities. Formation of the pyrazole derivatives was achieved by treating with Vilsmeier-Haack reagent. The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activities compared to Diclofenac sodium as standard drug. Compounds 4g, 4i and 4k exhibited the maximum anti-inflammatory and analgesic activities. The detailed synthesis, spectroscopic and toxicity data are reported.

  5. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  6. The effect of lipophilicity on the antibacterial activity of some 1-benzylbenzimidazole derivatives

    D. J. BARNA

    2008-10-01

    Full Text Available In the present paper, the antibacterial activity of some 1-benzylbenzimidazole derivatives were evaluated against the Gram-negative bacteria Escherichia coli. The minimum inhibitory concentration was determined for all the compounds. Quantitative structure–activity relationship (QSAR was employed to study the effect of the lipophilicity parameters (log P on the inhibitory activity. Log P values for the target compounds were experimentally determined by the “shake-flask” method and calculated by using eight different software products. Multiple linear regression was used to correlate the log P values and antibacterial activity of the studied benzimidazole derivatives. The results are discussed based on statistical data. The most acceptable QSAR models for the prediction of the antibacterial activity of the investigated series of benzimidazoles were developed. High agreement between the experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on the antibacterial activity of this class of compounds, which simplifies the design of new biologically active molecules.

  7. Antibacterial activity of RU 64004 (HMR 3004), a novel ketolide derivative active against respiratory pathogens.

    Agouridas, C; Bonnefoy, A; Chantot, J F

    1997-01-01

    The antibacterial activity of RU 64004, a new ketolide, was evaluated against more than 600 bacterial strains and was compared with those of various macrolides and pristinamycin. RU 64004 had good activity against multiresistant pneumococci, whether they were erythromycin A resistant or not, including penicillin-resistant strains. RU 64004 inhibited 90% of pneumococci resistant to erythromycin A and penicillin G at 0.6 and 0.15 microg/ml, respectively. Unlike macrolides, RU 64004 did not indu...

  8. Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives.

    Giraud, Francis; Alves, Georges; Debiton, Eric; Nauton, Lionel; Théry, Vincent; Durieu, Emilie; Ferandin, Yoan; Lozach, Olivier; Meijer, Laurent; Anizon, Fabrice; Pereira, Elisabeth; Moreau, Pascale

    2011-07-14

    The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents. PMID:21623630

  9. Synthesis, Antioxidant and Antimicrobial Activity of a New Phloridzin Derivative for Dermo-Cosmetic Applications

    Silvia Vertuani

    2012-11-01

    Full Text Available The phenolic compound phloridzin (phloretin 2′-O-glucoside, variously named phlorizin, phlorrhizin, phlorhizin or phlorizoside is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. Phloridzin is specifically found in apple and apple juice and known for its biological properties. In particular we were attracted by potential dermo-cosmetic applications. Here we report the synthesis, stability studies and antimicrobial activity of compound F2, a new semi-synthetic derivative of phloridzin. The new derivative was also included in finished formulations to evaluate its stability with a view to a potential topical use. Stability studies were performed by HPLC; PCL assay and ORAC tests were used to determine the antioxidant activity. F2 presented an antioxidant activity very close to that of the parent phloridzin, but, unlike the latter, was more stable in formulations. To further explore potential health claims, antifungal activity of phloridzin and its derivative F2 were determined; the results, however, were rather low; the highest value was 31,6% of inhibition reached by F2 on Microsporum canis at the highest dose.

  10. Synthesis and Insecticidal Activity of Novel Camptothecin Derivatives Containing Analogs of Chrysanthemic Acid Moieties

    DENG Li; ZHANG Lan; CAO Li-dong; XIE Ru-liang; ZHANG Yan-ning; HE Wei-zhi; JIANG Hong-yun

    2014-01-01

    Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin (CPT) and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin (1) and 10-hydroxycamptothecin (2) derivatives (1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e) were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua Hübner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.

  11. Ribulose Bisphosphate Carboxylase Activity in Anther-Derived Plants of Saintpaulia ionantha Wendl. Shag.

    Bhaskaran, S; Smith, R H; Finer, J J

    1983-11-01

    Plants obtained from anther culture of the African violet, Saintpaulia ionantha Wendl. ;Shag' and vegetatively cloned copies of the parent anther donor plant were examined for their ploidy and ribulose-1,5-biphosphate carboxylase (RuBPcase) activity. The cloned parent plants were all diploid and did not vary much in their nuclear DNA, chlorophyll, and RuBPcase activity. Some of the anther-derived plants were similar to the parent plants while others were not. Different levels of ploidy were observed among the androgenetic plants. RuBPcase activities higher than that of the parent plants were found in some anther-derived plants. However, there was no direct correlation between ploidy and RuBPcase activity. Expression of nuclear genes from a single parent in the anther-derived plants and it's diploidization or plastid changes during early stages of microsporogenesis or androgenesis are suggested as possible reasons for the variations observed among them. This could be a useful technique to obtain physiological variants which could be agronomically desirable. PMID:16663273

  12. Syntheses and In Vitro Biological Activity of Some Derivatives of C-9154 Antibiotic

    Isaac Asusheyi Bello

    2012-01-01

    Full Text Available In our continued attempts at designing new antibiotics based on the structure of the C-9154 antibiotic, to simultaneously improve activity and lower toxicity, an analogue to the C-9154 antibiotic and six derivatives of this analogue were synthesized. The approach was to significantly reduce the polarity of the synthesized analogue in the derivatives to achieve increased permeability across cell membranes by conversion of the highly polar carboxylic group to an ester functional group. The compounds were synthesized using a two-step reaction which involved an additional reaction between benzyl amine and maleic anhydride and then conversion of the terminal carboxylic acid functional group to an ester functional group using a thionyl chloride mediated esterification reaction. The compounds were fully characterized using Infrared, GC-MS, and 1D and 2D NMR experiments. The in vitro biological activity of the compounds showed that the derivatives were more active than the analogues as was anticipated with minimum inhibitory concentration in the range 0.625–5 μg/mL. The analogue had minimum inhibitory concentration in the range 2.5–10 μg/mL. These values are significantly better than that obtained for the original C-9154 antibiotic which had activity in the range 10–>100 μg/mL.

  13. Design, synthesis, antimicrobial activity and molecular modeling studies of novel benzofuroxan derivatives against Staphylococcus aureus.

    Jorge, Salomão Dória; Masunari, Andrea; Rangel-Yagui, Carlota Oliveira; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa

    2009-04-15

    Molecular modification is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N'-(benzofuroxan-5-yl)methylene]benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological profile. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 microg/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates. PMID:19324556

  14. Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives

    Barros, Francisco W.A. [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil); Bezerra, Daniel P., E-mail: danielpbezerra@gmail.com [Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe (Brazil); Ferreira, Paulo M.P. [Department of Biological Sciences, Federal University of Piauí, Picos, Piauí (Brazil); Cavalcanti, Bruno C. [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil); Silva, Teresinha G.; Pitta, Marina G.R.; Lima, Maria do C.A. de; Galdino, Suely L.; Pitta, Ivan da R. [Department of Antibiotics, Federal, University of Pernambuco, Recife, Pernembuco (Brazil); Costa-Lotufo, Letícia V.; Moraes, Manoel O. [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil); Burbano, Rommel R. [Institute of Biological Sciences, Federal University of Pará, Belém, Pará (Brazil); Guecheva, Temenouga N.; Henriques, João A.P. [Biotechnology Center, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul (Brazil); Pessoa, Cláudia, E-mail: cpessoa@ufc.br [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil)

    2013-04-01

    Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione — AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione — AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl) -1,3-thiazolidine-2,4-dione — AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2, 4-dione — AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways. - Highlights: ► Thiazacridine derivatives induce mitochondrial-dependent apoptotic cell death. ► Thiazacridine derivatives inhibit DNA topoisomerase I action. ► Thiazacridine derivatives failed to cause genotoxicity on human lymphocytes.

  15. Synthesis and Antibacterial Activity of Novel Levofloxacin Derivatives Containing a Substituted Thienylethyl Moiety

    Negar Mohammadhosseini

    2012-08-01

    Full Text Available Background and the purpose of the study Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities. Methods:The N-substituted analogs of levofloxacin 6a-j were prepared by nucleophilic reaction of Ndesmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria. Results:All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC = 0.04-6.25 mug/mL; however, the activity against Gram-negative bacteria was lower (MIC = 1.56-100 mug/mL. As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC = 0.04-0.19 mug/mL, and their activities were found to be 5-25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4. Conclusion:We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive chemotherapy.

  16. Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives

    Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione — AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione — AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl) -1,3-thiazolidine-2,4-dione — AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2, 4-dione — AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways. - Highlights: ► Thiazacridine derivatives induce mitochondrial-dependent apoptotic cell death. ► Thiazacridine derivatives inhibit DNA topoisomerase I action. ► Thiazacridine derivatives failed to cause genotoxicity on human lymphocytes

  17. Design, synthesis and anti-HIV activity of novel quinoxaline derivatives.

    Patel, Saloni B; Patel, Bhumika D; Pannecouque, Christophe; Bhatt, Hardik G

    2016-07-19

    In order to design novel anti-HIV agents, pharmacophore modelling, virtual screening, 3D-QSAR and molecular docking studies were performed. Pharmacophore model was generated using 17 structurally diverse molecules using DISCOtech followed by refinement with GASP module of Sybyl X. The best model containing four features; two donor sites, one acceptor atom and one hydrophobic region; was used as a query for virtual screening in NCI database and 6 compounds with Qfit value ≥98 were retrieved. The quinoxaline ring which is the bio-isostere of pteridine ring, retrieved as a hit in virtual screening, was selected as a core moiety. 3D-QSAR was carried on thirty five 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide derivatives. Contour map analysis of best CoMFA and CoMSIA model suggested incorporation of hydrophobic, bulky and electronegative groups to increase potency of the designed compounds. 50 quinoxaline derivatives with different substitutions were designed on basis of both ligand based drug design approaches and were mapped on the best pharmacophore model. From this, best 32 quinoxaline derivatives were docked onto the active site of integrase enzyme and in-silico ADMET properties were also predicted. From this data, synthesis of top 7 quinoxaline derivatives was carried out and were characterized using Mass, (1)H-NMR and (13)C-NMR spectroscopy. Purity of compounds were checked using HPLC. These derivatives were evaluated for anti-HIV activity on III-B strain of HIV-1 and cytotoxicity studies were performed on VERO cell line. Two quinoxaline derivatives (7d and 7e) showed good results, which can be further explored to develop novel anti-HIV agents. PMID:27105027

  18. Structure-activity of valencenoid derivatives and their repellence to the Formosan subterranean termite.

    Zhu, Betty C R; Henderson, Gregg; Sauer, Anne M; Yu, Ying; Crowe, William; Laine, Roger A

    2003-12-01

    Eight valencenoid derivatives were evaluated for their repelling activity against Formosan subterranean termites, Coptotermes formosanus Shiraki. Among them, 1,10-dihydronootkatone was the strongest repellent, and valencene was the weakest. Results of the structure-repellency relationships indicated (1) reduction of the ketone group to the alcohol on position 2 of nootkatone curtailed the activity; (2) because of the low activity of valencene relative to nootkatone that the ketone group was essential for repellent activity; (3) reduction of the 1,10 double bond (1,10-dihydronootkatone and tetrahydronootkatone) produced compounds more repellent than nootkatone; (4) the isopropenyl group probably does not participate in binding as evidenced by no significant difference in the repellent activity among nootkatone (double bond between position 11 and 12), isonootkatone (double bond between position 7 and 11), and 11,12-dihydronootkatone. PMID:14969356

  19. Antimicrobial Activity of Some Thiourea Derivatives and Their Nickel and Copper Complexes

    Cevdet Akbay

    2009-01-01

    Full Text Available Five thiourea derivative ligands and their Ni2+ and Cu2+ complexes have been synthesized. The compounds were screened for their in vitro anti-bacterial activity using Gram-positive bacteria (two different standard strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Bacillus cereus and Gram-negative bacteria (Esherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Proteus vulgaris, Enterobacter aerogenes and in vitro anti-yeast activity (Candida albicans, Candida krusei, Candida glabrata, Candida tropicalis, Candida parapsilosis. The minimum inhibitory concentration was determined for all ligands and their complexes. In vitro anti-yeast activity of both ligands and their metal complexes is greater than their in vitro anti-bacterial activity. The effect of the structure of the investigated compounds on the antimicrobial activity is discussed.

  20. Activated carbon derived from waste coffee grounds for stable methane storage

    Kemp, K. Christian; Baek, Seung Bin; Lee, Wang-Geun; Meyyappan, M.; Kim, Kwang S.

    2015-09-01

    An activated carbon material derived from waste coffee grounds is shown to be an effective and stable medium for methane storage. The sample activated at 900 °C displays a surface area of 1040.3 m2 g-1 and a micropore volume of 0.574 cm3 g-1 and exhibits a stable CH4 adsorption capacity of ˜4.2 mmol g-1 at 3.0 MPa and a temperature range of 298 ± 10 K. The same material exhibits an impressive hydrogen storage capacity of 1.75 wt% as well at 77 K and 100 kPa. Here, we also propose a mechanism for the formation of activated carbon from spent coffee grounds. At low temperatures, the material has two distinct types with low and high surface areas; however, activation at elevated temperatures drives off the low surface area carbon, leaving behind the porous high surface area activated carbon.

  1. Design, synthesis and antibacterial activity of isatin derivatives as FtsZ inhibitors

    Lian, Zhi-Min; Sun, Juan; Zhu, Hai-Liang

    2016-08-01

    Seven isatin derivatives have been designed, and their chemical structures were characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. These compounds were evaluated for antimicrobial activities. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding models. All of the compounds exhibited better antibacterial activities. Interestingly, compound 5c and 5d exhibited better antibacterial activities with IC50 values of 0.03 and 0.05 μmol/mL against Staphylococcus aureus, respectively. Compound 5g displays antibacterial activity with IC50 values of 0.672 and 0.830 μmol/mL against Escherichia coli and Pseudomonas aeruginosa, respectively.

  2. Anticancer Activity of Some New Synthesized Tetrahydroquinoline and Tetrahydrochromene Carbonitrile Derivatives

    Usama W. Hawas

    2011-01-01

    Full Text Available Problem statement: In continuation to our search for new heterocyclic chemistry based anticancer, the suggestion, synthesis, structure elucidation of some naphthalene, chromene and quinoline derivatives 3-7 were realized herein using 3-methylcyclohexanone 1 as a starting material. Approach: The antitumor activities of the newly synthesized compounds 4-7 were evaluated utilizing 60 different human tumor cell lines, representing leukemia, melanoma, lung, colon, brain, ovary, breast and prostate as well as kidney. Results: Some of the tested compounds exhibited better in vitro antitumor activities at low concentration (log10 GI50 = -4.7 against the used human tumor cell lines. Conclusion: From the obtained results, we can conclude that cyanopyridine and pyrane moieties fused to 3-methycyclohexane ring are essential for antitumor activities. In the present work, we can suggest that the anticancer activity is due to the presence of nitrogen heterocyclic rings and the presence of the nitrile groups (CN generally enhancing the activity.

  3. Synthesis and in vitro antibacterial and antifungal activities of benzoxazole derivatives

    The in vitro antibacterial and antifungal activities of twenty-nine (29) benzoxazole derivatives were tested against fifteen Gram-positive and sixteen Gram-negative strains. Out of the twenty-nine compounds, eighteen compounds 3-5, 7-9, 11-13, 15-25 showed a broad range of activity against tested Gram-positive microorganisms, whereas rest of the compounds 6, 10, 14 and 26-31 were found to be completely inactive against all the tested strains of Gram-positive bacteria. Five compounds 8, 11-13, and 15 showed activities against Gram-negative strains whereas the rest were devoid of any activity. Twenty-one (21) out of twenty-nine (29) compounds possessed antifungal activity. The structures of the synthetic compounds were confirmed by IR, EIMS and /sup 1/H-NMR spectral data. (author)

  4. Synthesis of Novel (E) -α-(methoxyimino) Benzeneacetate Derivatives and their Fungicidal Activities

    In order to find novel strobilurin derivatives with good fungicidal activities, a series of (E)-α-(methoxyimino)benzeneacetate analogues containing 1,2,4-triazole Schiff base moiety were designed and synthesized. Their structures were confirmed by IR,1H-NMR, HRMS or elemental analyses. The antifungal activities indicated that compounds 6 showed moderate to good fungicidal activities against Rhizoctonia solani, Botrytis cinereapers, Fusarium graminearum and Blumeria graminis at the concentration 50 μ g/mL. For example, compounds 6e and 6h exhibited promising antifungal activity against Rhizoctonia solani, Botrytis cinereapers and Fusarium graminearum. Compounds 6g and 6j had higher fungicidal activities against Blumeria graminis at the concentration of 50 μ g/ml, inhibitory rate is 95.32 percentage and 89.67 percentage, respectively. (author)

  5. Anticancer, Anti-Inflammatory, and Analgesic Activities of Synthesized 2-(Substituted phenoxy Acetamide Derivatives

    Priyanka Rani

    2014-01-01

    Full Text Available The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy-N-(1-phenylethylacetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer, SK-N-SH (neuroblastoma, anti-inflammatory activity, and analgesic activity. These investigations revealed that synthesized products 3a–j with halogens on the aromatic ring favors as the anticancer and anti-inflammatory activity. Among all, compound 3c N-(1-(4-chlorophenylethyl-2-(4-nitrophenoxyacetamide exhibited anticancer, anti-inflammatory, and analgesic activities. In conclusion, 3c may have potential to be developed into a therapeutic agent.

  6. Anticancer, anti-inflammatory, and analgesic activities of synthesized 2-(substituted phenoxy) acetamide derivatives.

    Rani, Priyanka; Pal, Dilipkumar; Hegde, Rahul Rama; Hashim, Syed Riaz

    2014-01-01

    The aphorism was to develop new chemical entities as potential anticancer, anti-inflammatory, and analgesic agents. The Leuckart synthetic pathway was utilized in development of novel series of 2-(substituted phenoxy)-N-(1-phenylethyl)acetamide derivatives. The compounds containing 1-phenylethylamine as basic moiety attached to substituted phenols were assessed for their anticancer activity against MCF-7 (breast cancer), SK-N-SH (neuroblastoma), anti-inflammatory activity, and analgesic activity. These investigations revealed that synthesized products 3a-j with halogens on the aromatic ring favors as the anticancer and anti-inflammatory activity. Among all, compound 3c N-(1-(4-chlorophenyl)ethyl)-2-(4-nitrophenoxy)acetamide exhibited anticancer, anti-inflammatory, and analgesic activities. In conclusion, 3c may have potential to be developed into a therapeutic agent. PMID:25197642

  7. Anti-Inflammatory Activity of Tanzawaic Acid Derivatives from a Marine-Derived Fungus Penicillium steckii 108YD142

    Hee Jae Shin; Gam Bang Pil; Soo-Jin Heo; Hyi-Seung Lee; Jong Seok Lee; Yeon-Ju Lee; Jihoon Lee; Ho Shik Won

    2016-01-01

    Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4), and K (5). The structures of tanzawaic acid derivatives 1–5 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis. These compounds significantly inhibited nitric oxide (NO) production a...

  8. Short communication: an in vitro assessment of the antibacterial activity of plant-derived oils.

    Mullen, K A E; Lee, A R; Lyman, R L; Mason, S E; Washburn, S P; Anderson, K L

    2014-09-01

    Nonantibiotic treatments for mastitis are needed in organic dairy herds. Plant-derived oils may be useful but efficacy and potential mechanisms of action of such oils in mastitis therapy have not been well documented. The objective of the current study was to evaluate the antibacterial activity of the plant-derived oil components of Phyto-Mast (Bovinity Health LLC, Narvon, PA), an herbal intramammary product, against 3 mastitis-causing pathogens: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis. Plant-derived oils evaluated were Thymus vulgaris (thyme), Gaultheria procumbens (wintergreen), Glycyrrhiza uralensis (Chinese licorice), Angelica sinensis, and Angelica dahurica. Broth dilution testing according to standard protocol was performed using ultrapasteurized whole milk instead of broth. Controls included milk only (negative control), milk + bacteria (positive control), and milk + bacteria + penicillin-streptomycin (antibiotic control, at 1 and 5% concentrations). Essential oil of thyme was tested by itself and not in combination with other oils because of its known antibacterial activity. The other plant-derived oils were tested alone and in combination for a total of 15 treatments, each replicated 3 times and tested at 0.5, 1, 2, and 4% to simulate concentrations potentially achievable in the milk within the pre-dry-off udder quarter. Thyme oil at concentrations ≥2% completely inhibited bacterial growth in all replications. Other plant-derived oils tested alone or in various combinations were not consistently antibacterial and did not show typical dose-response effects. Only thyme essential oil had consistent antibacterial activity against the 3 mastitis-causing organisms tested in vitro. Further evaluation of physiological effects of thyme oil in various preparations on mammary tissue is recommended to determine potential suitability for mastitis therapy. PMID:25022682

  9. Enhanced adsorption of perfluorooctane sulfonate and perfluorooctanoate by bamboo-derived granular activated carbon.

    Deng, Shubo; Nie, Yao; Du, Ziwen; Huang, Qian; Meng, Pingping; Wang, Bin; Huang, Jun; Yu, Gang

    2015-01-23

    A bamboo-derived granular activated carbon with large pores was successfully prepared by KOH activation, and used to remove perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) from aqueous solution. The granular activated carbon prepared at the KOH/C mass ratio of 4 and activation temperature of 900°C had fast and high adsorption for PFOS and PFOA. Their adsorption equilibrium was achieved within 24h, which was attributed to their fast diffusion in the micron-sized pores of activated carbon. This granular activated carbon exhibited the maximum adsorbed amount of 2.32mmol/g for PFOS and 1.15mmol/g for PFOA at pH 5.0, much higher than other granular and powdered activated carbons reported. The activated carbon prepared under the severe activation condition contained many enlarged pores, favorable for the adsorption of PFOS and PFOA. In addition, the spent activated carbon was hardly regenerated in NaOH/NaCl solution, while the regeneration efficiency was significantly enhanced in hot water and methanol/ethanol solution, indicating that hydrophobic interaction was mainly responsible for the adsorption. The regeneration percent was up to 98% using 50% ethanol solution at 45°C. PMID:24721493

  10. Mutagenic activity of some coal-derived humic compounds evaluated by the Ames test.

    Bernacchi, F; Ponzanelli, I; Barale, R; Loprieno, N

    1996-07-10

    Two coal-derived humic substances (Sulcis and South Africa, Eniricerche, Italy) have been evaluated for their mutagenic activity on TA98 and TA100 Salmonella typhimurium strains, either in presence or in absence of metabolic activation (S9). Both compounds showed no effect on the two strains, as observed with natural humic acid (Fluka). After chlorination, coal-derived humic acids induced a strong dose-related increase in the number of revertants on TA100 without S9, whose extent was directly proportional to the chlorination ratios. Such effect was completely suppressed when a sodium thiosulfate solution (10%) was added at the end of the chlorination period (about 90 h). The analogies with natural humic acid mutagenicity are discussed. PMID:8700175

  11. Mutagenic activity of some coal-derived humic compunds evaluated by the Ames test

    Bernacchi, F.; Ponzanelli, I.; Barale, R.; Loprieno, N. [Universita degli Studi di Pisa, Pisa (Italy). Dipt. Scienze dell`Ambiente e del Territorilo

    1996-07-10

    Two coal-derived humic substances were evaluated for their mutagenic activity on TA98 and TA100 Salmonella typhimurium strains, either in the presence or absence of metabolic activation (S9). Both compounds showed no effect on the two strains, as observed with natural humic acid (Fluka). After chlorination, coal-derived humic acids induced a strong dose-related increase in the number of revertants on TA100 without S9, whose extent was directly proportional to the chlorination ratios. Such effect was completely suppressed when a sodium thiosulphate solution (10%) was added at the end of the chlorination period (about 90 h). The analogies with natural humic acid mutagenicity are discussed. 19 refs., 5 tabs.

  12. [Anticoagulant activity of low-molecular-weight sulfated derivatives of galactomannan from Cyamopsis tetragonoloba (L.) seeds].

    Mestechkina, N M; Shcherbukhin, V D; Bannikova, G E; Varlamov, V P; Drozd, N N; Tolstenkov, A S; Makarov, V A; Tikhonov, V E

    2008-01-01

    Galactomannan from seeds of Cyamopsis tetragonoloba (L.) Taub. (guar) was depolymerized using immobilized enzymatic preparation celloviridin. A set of fragments whose molecular weights varied from 12.6 to 245.6 kDa was obtained. Sulfated derivatives of components of all fractions were synthesized, in which the content of HSO3(-) groups was 48.05% +/- 2.31. All preparations exhibited anticoagulant activity, which was recorded in vitro in two tests--aIIa and aXa. The antithrombin activity (aIIa) was high (up to 65-87 U/mg) and did not depend on the molecular weight of a sulfated derivative; in the second test (aXa), the effect of molecular weight was observed. Biospecific electrophoresis allowed us to detect the ability of galactomannan sulfates to form complexes with protamine sulfate, a classic antidote to heparin. PMID:18491607

  13. Synthesis and Anti-tumor Activity of Novel Glycyrrhetinic Acid Derivatives

    MENG Yan-qiu; DING Jia-qi; LIU Yuan; NIE Hui-hui; GUAN Sai; ZOU Chao; ZHAO Na; CHEN Hong; CAO Bo

    2012-01-01

    Twenty-five derivatives of glycyrrhetinic acid(GA)modified on the A-ring,at C30 and C11 positions were synthesized.Their in vitro cytotoxicity against various cancer cell lines[henrietta lacks strain of cancer cells(HeLa),human hepatocellular liver carcinoma cells(HepG2)and human gastric carcinoma cells(BGC-823)]was evaluated by standard MTT[3-(4,5-dimethyl-2-thiazol-yl)-2,5-diphenyl-2H-tetrazolium bromide]assay.All the tested derivatives were found to have stronger cell growth inhibitory than their parent compound GA.Among them,compounds 3a,5a,and 8d have similar activity on HeLa cell line,and compound 8a has similar activity on HeLa,HepG2 and BGC-823 cell lines as Gefitinib.

  14. Tumor-derived vaccines containing CD200 inhibit immune activation: implications for immunotherapy.

    Xiong, Zhengming; Ampudia-Mesias, Elisabet; Shaver, Rob; Horbinski, Craig M; Moertel, Christopher L; Olin, Michael R

    2016-09-01

    There are over 400 ongoing clinical trials using tumor-derived vaccines. This approach is especially attractive for many types of brain tumors, including glioblastoma, yet so far the clinical response is highly variable. One contributor to poor response is CD200, which acts as a checkpoint blockade, inducing immune tolerance. We demonstrate that, in response to vaccination, glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune tolerance. The addition of the CD200 inhibitor significantly increased leukocyte infiltration into the vaccine site, cytokine and chemokine production, and cytolytic activity. Our data therefore suggest that CD200 suppresses the immune system's response to vaccines, and that blocking CD200 could improve the efficacy of cancer immunotherapy. PMID:27485078

  15. [The influence of docosahexaenoic acid moiety on cytotoxic activity of 1,2,4-thiadiazole derivatives].

    Akimov, M G; Gretskaia, N M; Karnoukhova, V A; Serkov, I V; Proshin, A N; Shtratnikova, V Iu; Bezuglov, V V

    2014-01-01

    Among 3-(2-aminopropyl)-1,2,4-thiadiazole derivatives contatining substitution-ready secondary amino group and exhibiting cytotoxic towards rat C 6 glioma cells three compounds with LD 50 values ranged from 6 to 48 мM were chosen. For these compounds amides with docosahexaenoic acid were synthetised and their cytotoxic activity was studied. It was shown that, although docosahexaenoic acid itself was not toxic for C 6 glioma cells, its addition to the amino derivatives of 1,2,4-thiadiazole increased or decreased resultant cytotoxicity. The effect depended on the structure of 1,2,4-thiadiazole substituents. The obtained data show that the acylation of cytotoxic compounds with docosahexaenoic acid does not necessarily lead to the increase of their activity, but sometimes can inactivate a compound. This fact should be taken into account, especially in the case of anti-cancer drug development. PMID:25249531

  16. Synthesis, Spectral Characterization and biological activity of N-Substituted Derivatives of Tetrahydrofuran-2-ylmethylamine

    Aziz-ur-Rehman; Rasool, S; Abbasi, M. A.; Khan, K. M.; Ahmad, I.; 2S. Afzal

    2014-01-01

    Tetrahydrofuran-2-ylmethylamine (1) was subjected to condensation reaction with 4-chlorobenzenesulfonyl chloride (2) in a mild basic medium to synthesize N-(tetrahydrofuran-2-ylmethyl)-4-chlorobenzenesulfonamide (3). A series of N-substituted derivatives, 5a-f, were synthesized by condensing alkyl/aralkyl halides, 4a-f, with 3 under polar aprotic conditions using sodium hydride activator. The spectral characterization of all the molecules included IR, 1H-NMR and EI-MS data. The biological act...

  17. Effect of vanillin and its acid and alcohol derivatives on the diphenolase activity of mushroom tyrosinase

    Masoomeh Bagheri-Kalmarzi; Sajedi, Reza H.; Elham Asadollahi; Nosrat O. Mahmoodi; Reza Haji-Hosseini

    2012-01-01

    For the first time in the present study the effects of vanillin, vanillyl alcohol, vanillic acid, as well as the newly synthesized vanillin derivative, bis-vanillin, were investigated on the oxidation of dopamine hydrochloride by mushroom tyrosinase. Among them, vanillin and bis-vanillin act as activators, while vanillyl alcohol and vanillic acid exhibited inhibitory effects, the IC50 values being estimated 1.5 and 1.0 mM, respectively. These compounds were mixed inhibitors. The presence of a...

  18. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric ...

  19. Fluorescein dye derivatives and their nanohybrids: Synthesis, characterization and antimicrobial activity.

    Negm, Nabel A; Abou Kana, Maram T H; Abd-Elaal, Ali A; Elwahy, Ahmed H M

    2016-09-01

    Fluorescein (resorcinolphthalein) is a synthetic organic photoactive dye compound soluble in water, alcohol and polar solvents. It is widely used as a fluorescent tracer in medicinal and biological applications and tumor infected tissues tracer. In this study, fluorescein (F) was condensed by five coupling agents namely: p,p-phenylene diamine, p-hydroxy aniline, o-hydroxy aniline, p-methoxy aniline and p-methyl aniline in a molar ratio of 2(F):1 (coupling agent). The chemical structures of the synthesized fluorescein derivatives were confirmed using: microelemental analysis, FTIR spectroscopy, 1H-NMR spectroscopy, and mass spectroscopy. The synthesized compounds were loaded on chemically prepared silver nanoparticles via reduction reaction of silver nitrate. The structures and properties of the formed fluorescein derivatives silver nanohybrids were determined using: UV/Vis spectroscopy, TEM images and dynamic light scattering (DLS). The synthesized compounds and their nanohybrids were evaluated for their antimicrobial activities against different bacterial strains and fungi. The results showed that the formed fluorescein derivatives silver nanohybrids are in moderate diameter range, and the loading of the synthesized compounds protect the silver nanoparticles against coagulation. The antimicrobial activity against the studied microorganisms was comparable to the standard used. Moreover, the antimicrobial activity was increased considerably in case of using fluorescein derivatives silver nanohybrids. The antimicrobial activities were correlated to the chemical structures of the compounds, diameter of the formed nanohybrids and to the nature of the tested bacterial strains. The mechanism of the antimicrobial action of the synthesized compounds and their nanohybrids was proposed. PMID:27450296

  20. Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity.

    Wróbel, Tomasz M; Kosikowska, Urszula; Kaczor, Agnieszka A; Andrzejczuk, Sylwia; Karczmarzyk, Zbigniew; Wysocki, Waldemar; Urbańczyk-Lipkowska, Zofia; Morawiak, Maja; Matosiuk, Dariusz

    2015-01-01

    Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenyl)imidazolidine-1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using molecular modelling. It was found to be similar to that of fluconazole. The potential for further optimization including SAR of the compound is briefly discussed. PMID:26287137

  1. Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity

    Tomasz M. Wróbel

    2015-08-01

    Full Text Available Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenylimidazolidine-1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using molecular modelling. It was found to be similar to that of fluconazole. The potential for further optimization including SAR of the compound is briefly discussed.

  2. Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives

    Sinara Mônica Vitalino de Almeida; Elizabeth Almeida Lafayette; Lúcia Patrícia Bezerra Gomes da Silva; Cézar Augusto da Cruz Amorim; Tiago Bento de Oliveira; Ana Lucia Tasca Gois Ruiz; João Ernesto de Carvalho; Ricardo Olímpio de Moura; Eduardo Isidoro Carneiro Beltrão; Maria do Carmo Alves de Lima; Luiz Bezerra de Carvalho Júnior

    2015-01-01

    In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a–h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as re...

  3. Synthesis of novel kavain-like derivatives and evaluation of their cytotoxic activity

    Palladium-catalyzed cross coupling reactions (Sonogashira-Hagihara, Suzuki-Miyaura, and Heck) coupling and nickel hydride-mediated tandem isomerization aldolisation have been used for the synthesis of three series of δ-valerolactones substituted in positions 3, 4, 5 and 6 of the lactone ring. The 26 kavaien-like derivatives were tested against three cell lines and five of them exhibited a weak cytotoxic activity. (author)

  4. Synthesis of Some New Quinazolinone Derivatives and Evaluation of Their Antimicrobial Activities

    Khodarahmi, Ghadamali; Jafari, Elham; Hakimelahi, Gholamhossein; Abedi, Daryoush; Rahmani Khajouei, Marzieh; Hassanzadeh, Farshid

    2012-01-01

    Wide range of quinazolinone biological properties including: antibacterial, anticancer, and anti-inflammatory activities encouraged us to synthesis some fused quinazolinone derivatives. Anthranilic acid was condensed with chloro acylchloride followed by dehydration to form the benzoxazinone intermediate; subsequent addition of an amine provided the fused quinazolinones. Deoxyvasicinone which was previously synthesized by a multi step complex reactions was prepared in three steps using the fol...

  5. Synthesis, antibacterial and antifungal activity of some derivatives of 2-phenyl-chromen-4-one

    Sayed Alam

    2004-11-01

    Some derivatives of 2-phenyl-chromen-4-one (flavone ring) have been synthesized and tested for antibacterial and antifungal activities along with their chalcone precursors against four human pathogenic bacteria and five plant mould fungi. The structures of the synthesized compounds were elucidated by UV, IR and 1H NMR spectroscopic techniques, and elemental analysis. The antibacterial and antifungal screens of the synthesized compounds were performed in vitro by the filter paper disc diffusion method and the poisoned food technique.

  6. Novel Cycloheximide Derivatives Targeting the Moonlighting Protein Mip Exhibit Specific Antimicrobial Activity Against Legionella pneumophila

    Rasch, Janine; Theuerkorn, Martin; Ünal, Can; Heinsohn, Natascha; Tran, Stefan; Fischer, Gunter; Weiwad, Matthias; Steinert, Michael

    2015-01-01

    Macrophage infectivity potentiator (Mip) and Mip-like proteins are virulence factors in a wide range of pathogens including Legionella pneumophila. These proteins belong to the FK506 binding protein (FKBP) family of peptidyl-prolyl-cis/trans-isomerases (PPIases). In L. pneumophila, the PPIase activity of Mip is required for invasion of macrophages, transmigration through an in vitro lung–epithelial barrier, and full virulence in the guinea pig infection model. Additionally, Mip is a moonlighting protein that binds to collagen IV in the extracellular matrix. Here, we describe the development and synthesis of cycloheximide derivatives with adamantyl moieties as novel FKBP ligands, and analyze their effect on the viability of L. pneumophila and other bacteria. All compounds efficiently inhibited PPIase activity of the prototypic human FKBP12 as well as Mip with IC50-values as low as 180 nM and 1.7 μM, respectively. Five of these derivatives inhibited the growth of L. pneumophila at concentrations of 30–40 μM, but exhibited no effect on other tested bacterial species indicating a specific spectrum of antibacterial activity. The derivatives carrying a 3,5-dimethyladamantan-1-[yl]acetamide substitution (MT_30.32), and a 3-ethyladamantan-1-[yl]acetamide substitution (MT_30.51) had the strongest effects in PPIase- and liquid growth assays. MT_30.32 and MT_30.51 were also inhibitory in macrophage infection studies without being cytotoxic. Accordingly, by applying a combinatorial approach, we were able to generate novel, hybrid inhibitors consisting of cycloheximide and adamantane, two known FKBP inhibitors that interact with different parts of the PPIase domain, respectively. Interestingly, despite the proven Mip-inhibitory activity, the viability of a Mip-deficient strain was affected to the same degree as its wild type. Hence, we also propose that cycloheximide derivatives with adamantyl moieties are potent PPIase inhibitors with multiple targets in L

  7. Activity Coefficient Derivatives of Ternary Systems Based on Scatchard's Neutral Electrolyte description

    Miller, D G

    2007-05-16

    Activity coefficient derivatives with respect to molality are presented for the Scatchard Neutral Electrolyte description of a ternary common-ion electrolyte system. These quantities are needed for the calculation of 'diffusion Onsager coefficients' and in turn for tests of the Onsager Reciprocal Relations in diffusion. The usually-omitted b{sub 23} term is included. The direct SNE binary approximations and a further approximation are discussed. Binary evaluation strategies other than constant ionic strength are considered.

  8. Comparative Angiogenic Activities of Induced Pluripotent Stem Cells Derived from Young and Old Mice

    Suzuki, Hirohiko; Shibata, Rei; Kito, Tetsutaro; Yamamoto, Takashi; Ishii, Masakazu; Nishio, Naomi; Ito, Sachiko; Isobe, Ken-ichi; Murohara, Toyoaki

    2012-01-01

    Advanced age is associated with decreased stem cell activity. However, the effect of aging on the differentiation capacity of induced pluripotent stem (iPS) cells into cardiovascular cells has not been fully clarified. We investigated whether iPS cells derived from young and old mice are equally capable of differentiating into vascular progenitor cells, and whether these cells regulate vascular responses in vivo. iPS cells from mouse embryonic fibroblasts (young) or 21 month-old mouse bone ma...

  9. Deriving Derivatives

    Soklakov, Andrei N.

    2013-01-01

    Quantitative Structuring is a rigorous framework for the design of financial products. We show how it incorporates traditional investment ideas while supporting a more accurate expression of clients' views on the market. We briefly touch upon adjacent topics regarding the safety of financial derivatives and the role of pricing models in product design.

  10. Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives.

    Horita, Yasuhiro; Takii, Takemasa; Kuroishi, Ryuji; Chiba, Taku; Ogawa, Kenji; Kremer, Laurent; Sato, Yasuo; Lee, YooSa; Hasegawa, Tomohiro; Onozaki, Kikuo

    2011-02-01

    The present study was undertaken to optimize the anti-tubercular activity of 2-acetamido-2-deoxy-β-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313, Glc-NAc-DMDC), a lead compound previously reported by us. Structural modifications of OCT313 included the replacements of the DMDC group at C-1 by pyrrolidine dithiocarbamate (PDTC) and the acetyl group at C-2 by either propyl, butyl, benzyl or oleic acid groups. The antimycobacterial activities of these derivatives were evaluated against Mycobacterium tuberculosis (MTB). Glc-NAc-pyrrolidine dithiocarbamate (OCT313HK, Glc-NAc-PDTC) exhibited the most potent anti-tubercular activity with the minimal inhibitory concentration (MIC) of 6.25-12.5 μg/ml. The antibacterial activity of OCT313HK was highly specific to MTB and Mycobacterium bovis BCG, but not against Mycobacterium avium, Mycobacterium smegmatis, Staphylococcus aureus or Escherichia coli. Importantly, OCT313HK was also effective against MTB clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Interestingly, OCT313HK was exerted the primary bactericidal activity, and it was also exhibited the bacteriolytic activity at high concentrations. We next investigated whether the mycobacterial monooxygenase EthA, a common activator of thiocarbamide-containing anti-tubercular drugs, also activated OCT313HK. Contrary to our expectations, the anti-tubercular activity of dithiocarbamate sugar derivatives and dithiocarbamates were not dependent on ethA expression, in contrast to thiocarbamide-containing drugs. Overall, this study presents OCT313HK as a novel and potent compound against MTB, particularly promising to overcome drug resistance. PMID:21232949

  11. Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM Analyses

    Yahia Nasser Mabkhot

    2016-02-01

    Full Text Available Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6–8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, 1H-13C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn’t guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

  12. Effect of vanillin and its acid and alcohol derivatives on the diphenolase activity of mushroom tyrosinase

    Masoomeh Bagheri-Kalmarzi

    2012-01-01

    Full Text Available For the first time in the present study the effects of vanillin, vanillyl alcohol, vanillic acid, as well as the newly synthesized vanillin derivative, bis-vanillin, were investigated on the oxidation of dopamine hydrochloride by mushroom tyrosinase. Among them, vanillin and bis-vanillin act as activators, while vanillyl alcohol and vanillic acid exhibited inhibitory effects, the IC50 values being estimated 1.5 and 1.0 mM, respectively. These compounds were mixed inhibitors. The presence of aldehyde and metoxy groups at the meta position of aromatic compounds seems to cause them to react as tyrosinase activators, as observed in the case of vanillin and bis-vanillin. The presence of both groups in bis-vanillin results in a stronger activation effect compared to vanillin. The results indicate that the electron-withdrawing capacity of the functional group at the C-1 position is essential for the inhibitory potency of vanillin derivatives. In comparison with other benzoic acid derivatives, the results obtained in this study suggest that the relative positioning of hydroxy and methoxy groups at meta and para positions plays an important role in the inhibition effects of benzoic acids and their inhibition potency.

  13. Synthesis and characterization of 3-aminoquinoline derivatives and studies of photophysicochemical behaviour and antimicrobial activities

    Zengin, Gulay; Nafea Al Kawaz, Ali Muayad; Zengin, Huseyin; Mert, Adem; Kucuk, Bedia

    2016-01-01

    A series of 3-aminoquinoline derivatives were synthesized, where their chemical structures were confirmed by various analytical techniques, such as, Elemental Analysis, Nuclear Magnetic Resonance Spectroscopy (1H and 13C NMR), Liquid Chromatography-Mass-Mass Spectroscopy (LC-MS-MS), Ultraviolet-Visible Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FTIR) and Photoluminescence (PL). The quinoline ring core, typical of aminoquinolines, and a naphthalene group was combined to devise (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives. These derivatives were designed and synthesized in light of the chemical and biological profiles of these important subunits. All the compounds were evaluated for their in vitro antibacterial and antifungal activities by the paper disc diffusion method with Gram-positive Bacillus subtilis, Bacillus megaterium and Staphylococcus aureus, Gram-negative Enterobacter aerogenes, Eschericha coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and yeasts Candida albicans, Saccharomyces cerevisiae and Yarrovia lipolytica. These compounds showed antimicrobial activities against Gram-positive and Gram-negative bacteria and several yeasts, and thus their activity was not restricted to any particular type of microorganism.

  14. Synthesis, Spectral Characterization and biological activity of N-Substituted Derivatives of Tetrahydrofuran-2-ylmethylamine

    Aziz-ur-Rehman

    2014-06-01

    Full Text Available Tetrahydrofuran-2-ylmethylamine (1 was subjected to condensation reaction with 4-chlorobenzenesulfonyl chloride (2 in a mild basic medium to synthesize N-(tetrahydrofuran-2-ylmethyl-4-chlorobenzenesulfonamide (3. A series of N-substituted derivatives, 5a-f, were synthesized by condensing alkyl/aralkyl halides, 4a-f, with 3 under polar aprotic conditions using sodium hydride activator. The spectral characterization of all the molecules included IR, 1H-NMR and EI-MS data. The biological activity evaluation rendered 5c as moderate inhibitor of all the bacterial strains.

  15. Facile synthesis, characterization and antimicrobial activities of diphenylphosphoryl derivatives of substituted aryl and nitrogen heterocycles

    G. Subba Reddy

    2013-03-01

    Full Text Available Diphenylphosphoryl derivatives of substituted aryl and nitrogen heterocycles were prepared by a one-pot process involving sequential reaction of diphenylphosphine chloride with dry methyl alcohol/ethyl alcohol and then with different halides of substituted nitrogen heterocycles/aryl halides. The title compounds (5a-j structures were established by analytical, IR, NMR ( 1H, 13C and 31P and mass spectra, and they have been screened for their antimicrobial activity. They exhibited significant antibacterial and antifungal activity.

  16. Synthesis and in vitro antioxidant activity of quinolin-5-ylamine derivatives

    L. Mallesha

    2013-07-01

    Full Text Available Imines of six new quinolin-5-ylamine derivatives 3(a-c and 5(a-c were synthesized by the reaction of quinolin-5-ylamine (1 with different aldehydes 2(a-c and ketones 4(a-c. The chemical structures of the compounds were confirmed by UV-visible, FT-IR and 1H NMR spectral study. New compounds were screened for the antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl method. Butylated Hydroxytoluene (BHT was used as standard. All the compounds showed DPPH radical scavenging activity, where compound 3c was the best radical scavenger.

  17. Synthesis and in vitro antioxidant activity of quinolin-5-ylamine derivatives

    Mallesha, L.; B. K. Kendagannaswamy; K. N. Mohana

    2013-01-01

    Imines of six new quinolin-5-ylamine derivatives 3(a-c) and 5(a-c) were synthesized by the reaction of quinolin-5-ylamine (1) with different aldehydes 2(a-c) and ketones 4(a-c). The chemical structures of the compounds were confirmed by UV-visible, FT-IR and 1H NMR spectral study. New compounds were screened for the antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Butylated Hydroxytoluene (BHT) was used as standard. All the compounds showed DPPH radical scavenging activity...

  18. Highly Accurate Derivatives for LCL-Filtered Grid Converter with Capacitor Voltage Active Damping

    Xin, Zhen; Loh, Poh Chiang; Wang, Xiongfei;

    2016-01-01

    The middle capacitor voltage of an LCL-filter, if fed back for synchronization, can be used for active damping. An extra sensor for measuring the capacitor current is then avoided. Relating the capacitor voltage to existing popular damping techniques designed with capacitor current feedback would...... then proposed, based on either second-order or non-ideal generalized integrator. Performances of these derivatives have been found to match the ideal “s” function closely. Active damping based on capacitor voltage feedback can therefore be realized accurately. Experimental results presented have...

  19. Comparative Study on the Antioxidant and Anti-Toxoplasma Activities of Vanillin and Its Resorcinarene Derivative

    Oliveira, Claudio; Meurer, Ywlliane; Oliveira, Marianne; Medeiros, Wendy; Silva, Francisco; Brito, Ana; Pontes, Daniel; Andrade-Neto, Valter

    2014-01-01

    2,000 µg/mL). The in vivo acute toxicity assays of vanillin and resvan exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg during the first 30 min, 24 h or 14 days after administration. The obtained derivative showed greater antioxidative activity (84.9%) when comparing to vanillin (19.4%) at 1,000 μg/mL. In addition, vanillin presents anti-Toxoplasma activity, while resvan does not show that feature. Our findings suggest that this par...

  20. Synthesis and biological activity of pyrimido [1, 2-a] quinoline moiety and its 2-substituted derivatives

    Jadhav, A. G.; Halikar, N. K.

    2013-04-01

    2-Amino-3-cyano quinoline (1) and bis (methylthio) methylene malononitrile (2) were refluxed in N,N-dimethyl formamide (DMF) in presence of catalytic amount of anhydrous potassium carbonate to afforded 3, 11-dicyano-4-imino-2-methylthio -4H-pyrimido [1, 2-a] quinoline (3). The latter were further reacted with different substituted aniline, phenol, hetryl amine and compound containing active methyl group. Afforded to 3, 11-dicyano-4-imino -4H-pyrimido [1, 2-a] quinoline and their 2-substuited derivatives (4a-7c). All these newly synthesized compounds were characterized by elemental analysis and spectral data, and screened for their antimicrobial activities.

  1. Inhibition of Heme Peroxidase During Phenol Derivatives Oxidation. Possible Molecular Cloaking of the Active Center

    Juozas Kulys

    2005-10-01

    Full Text Available Abstract: Ab initio quantum chemical calculations have been applied to the study of the molecular structure of phenol derivatives and oligomers produced during peroxidasecatalyzed oxidation. The interaction of substrates and oligomers with Arthromyces ramosus peroxidase was analyzed by docking methods. The most possible interaction site of oligomers is an active center of the peroxidase. The complexation energy increases with increasing oligomer length. However, the complexed oligomers do not form a precise (for the reaction hydrogen bonding network in the active center of the enzyme. It seems likely that strong but non productive docking of the oligomers determines peroxidase inhibition during the reaction.

  2. Effects of resveratrol, curcumin and their derivatives on the activation of microglia induced by LPS

    YANG Jing-yu; MENG Xue-lian; ZHANG Li-jia; CHEN Guo-liang; WU Chun-fu

    2008-01-01

    Objective To determine the inhibitory effects of 21 resveratrol derivatives and 3 natural eureumiholds on lipopolysaccharide (LPS)-induced Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) production in mieroglia and their structure-activity relationships. Methods Cell viability was evaluated by the MTT reduction assay. Accumulation of nitrite (NO2-) in culture supernatant fluids was measured by the Griess reaction. Sodium nitroprusside (SNP) (2.5 mM) solution was used to determine the scavenging activities of these compounds. The levels of TNF-α in the culture medium were measured by using an ELISA kit. Semi-quantitative RT-PCR analysis was used to determine the mRNA levels of inducible NOS (iNOS) and TNF-α. Results It was found, for the first time, that certain resveratrol derivatives that have 3, 5-dimethoxyl groups in the A-ring, such as (E)-4- (3, 5-dimethoxystyryl) phenol (pterostilbene, compound 2), or have substituted the B-ring of resveratrol with quinolyl, such as (E)-5-[2-(quinolin-4-yl)vinyl] benzene-1, 3-diol (compound 18) and (E)-4-(3, 5-dimethoxystyryl)quinoline (compound 19), strongly inhibited NO production. Compounds 2, 18, and 19 reduced LPS-induced protein and mRNA expression of inducible NO synthase (iNOS), but did not display direct NO-scavenging activity up to 30 μM in sodium nitroprusside (SNP) solution. Moreover, compounds 2, 18, and 19 could also significantly inhibit the production of TNF-α by LPS-activated microglia. Furthermore, we found the demethoxy derivatives of eurcumin have more potent inhibition activity on NO and TNF-α releasing in activated-microglia. Conclusions In the present study we compared the activated-rnicroglia inhibition effect of resvertrol, curcumin and their derivatives and provided a glance of the structure-activity relationships of these compounds, the information is beneficial to design new potent compounds which can provide better therapeutic implications for various neurodegenerative diseases.

  3. Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation.

    Ma, Chunhua; Cao, Jiangying; Liang, Xuewu; Huang, Yongxue; Wu, Ping; Li, Yingxia; Xu, Wenfang; Zhang, Yingjie

    2016-01-27

    Aminopeptidase N (APN/CD13) over-expressed on tumor cells and tumor microenvironment, plays critical roles in tumor invasion, metastasis and angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel leucine ureido derivatives as aminopeptidase N (APN/CD13) inhibitors. The results showed that compound 7a had the most potent inhibitory activity against APN with the IC50 value of 20 nM, which could be used for further anticancer agent research. PMID:26629857

  4. Screening of biological activities of a series of chalcone derivatives against human pathogenic microorganisms.

    Karaman, Isa; Gezegen, Hayreddin; Gürdere, M Burcu; Dingil, Alparslan; Ceylan, Mustafa

    2010-02-01

    In an effort to develop new antimicrobial agents, a series of chalcone derivatives, 3-60, were prepared by Claisen-Schmidt condensation of appropriate acetophenones and 2-furyl methyl ketones with appropriate aromatic aldehydes, furfural, and thiophene-2-carbaldehyde in an aqueous solution of NaOH and EtOH at room temperature. The synthesized compounds were characterized by means of their IR- and NMR-spectral data, and elemental analysis. All compounds were tested for their antibacterial and antifungal activities by the disc diffusion method. For the most active compounds, also minimum inhibitory concentrations (MICs) were determined. PMID:20151389

  5. Plant derived substances with anti-cancer activity: from folklore to practice

    Marcelo eFridlender; Yoram eKapulnik; Hinanit eKoltai

    2015-01-01

    Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. I...

  6. Plant derived substances with anti-cancer activity: from folklore to practice

    Fridlender, Marcelo; Kapulnik, Yoram; Koltai, Hinanit

    2015-01-01

    Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70–95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early nineteenth century. This trend led to the discovery of different active compounds that are derived from pla...

  7. Barbiturate bearing aroylhydrazine derivatives: Synthesis, NMR investigations, single crystal X-ray studies and biological activity

    Giziroglu, Emrah; Sarikurkcu, Cengiz; Aygün, Muhittin; Basbulbul, Gamze; Soyleyici, H. Can; Firinci, Erkan; Kirkan, Bulent; Alkis, Ayse; Saylica, Tayfur; Biyik, Halil

    2016-03-01

    A series of barbituric acid aroylhydrazine derivatives have been prepared from their corresponding 1,3-dimethyl-5-acetyl barbituric acid and aroylhydrazines. All compounds have been fully characterized by using FT-IR, multinuclear NMR (1H, 13C) and Mass (MS) spectrometry. We also describe the X-ray crystal structure of 3a, which crystallizes in the monoclinic P21/n space group. The crystal structure is stabilized with infinite linear chains of dimeric units. Furthermore, all compounds were investigated for their tyrosinase inhibition, antioxidative and antimicrobial activies. The results from biological activity assays have shown that all of compounds have excellent antioxidant, significant tyrosinase inhibition and moderate antimicrobial activity.

  8. Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation on cytotoxic activities.

    Luo, Yan; Wang, Ke; Zhang, Meng-han; Zhang, Da-yong; Wu, Yang-chang; Wu, Xiao-ming; Hua, Wei-yi

    2015-06-01

    There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs. PMID:25913115

  9. Antitumoral, antileishmanial and antimalarial activity of pentacyclic 1,4-naphthoquinone derivatives

    Silva, Alcides J.M. da; Netto, Chaquip D.; Costa, Paulo R.R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nucleo de Pesquisas de Produtos Naturais. Lab. de Quimica Bioorganica]. E-mail: lqb@nppn.ufrj.br; Pacienza-Lima, Wallace; Rossi-Bergmann, Bartira; Maurel, Severine; Valentin, Alexis; Costa, Paulo R.R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho; Torres-Santos, Eduardo Caio [Instituto Oswaldo Cruz, Rio de Janeiro, RJ (Brazil). Lab. de Bioquimica de Tripanosomatideos; Maurel, Severine; Valentin, Alexis [Universite Paul Sabatier, Toulouse (France). Faculte de Pharmacie. Pharmacochimie des Substances Naturelles et Pharmacophores Redox

    2009-07-01

    Pterocarpanquinones 8a-c, previously synthesized in our laboratory, and an homologous series of derivatives, compounds 9a-c prepared in this work, were evaluated on breast cancer cells (MCF-7) and on the parasites Leishmania amazonensis and Plasmodium falciparum, in culture. Compounds 8a-c were more potent than 9a-c on tumor cells and Leishmania amazonensis. On the other hand, 9a-c showed to be more active on Plasmodium falciparum. All the compounds studied were bioselective, presenting negligible cytotoxicity against fresh murine lymphocytes and human lymphocytes activated by the mitogen phytohemagglutinin (PHA). (author)

  10. Cytotoxicity of phenothiazine derivatives associated with mitochondrial dysfunction: A structure-activity investigation

    Highlights: • Phenothiazines induced cell death in a concentration dependent manner in HTC cells. • Structural requirements that account to phenothiazine cytotoxicity were determined. • Phenothiazines promote immediate morphological changes in cultured liver cells. • Phenothiazine-induced cell death was accompanied of plasma membrane permeabilization. • The dissipation of mitochondrial membrane potential and permeabilization correlated with cytotoxicity. - Abstract: Phenothiazine derivatives are neuroleptic drugs used in the treatment of schizophrenia and anxiety. Several side effects are described for these drugs, including hepatotoxicity, which may be related to their cytotoxic activity. Working with isolated rat liver mitochondria, we previously showed that phenothiazine derivatives induced the mitochondrial permeability transition associated with cytochrome c release. Since the mitochondrial permeabilization process plays a central role in cell death, the aim of this work was to evaluate the effects of five phenothiazine derivatives (chlorpromazine, fluphenazine, thioridazine, trifluoperazine, and triflupromazine) on the viability of hepatoma tissue culture (HTC) cells to establish the structural requirements for cytotoxicity. All phenothiazine derivatives decreased the viability of the HTC cells in a concentration-dependent manner and exhibited different cytotoxic potencies. The EC50 values ranged from 45 to 125 μM, with the piperidinic derivative thioridazine displaying the most cytotoxicity, followed by the piperazinic and aliphatic derivatives. The addition of the phenothiazine derivatives to cell suspensions resulted in significant morphological changes and plasma membrane permeabilization. Octanol/water partition studies revealed that these drugs partitioned preferentially to the apolar phase, even at low pH values (≤4.5). Also, structural and electronic properties were calculated employing density functional theory. Interestingly, the

  11. Piperitone-derived saturated lactones: synthesis and aphid behavior-modifying activity.

    Grudniewska, Aleksandra; Dancewicz, Katarzyna; Białońska, Agata; Wawrzeńczyk, Czesław; Gabryś, Beata

    2013-04-10

    Two racemic and two enantiomeric pairs of new saturated lactones with the p-menthane system were obtained. The lactones were synthesized from racemic and enantiomerically enriched cis- and trans-piperitols, which were obtained from piperitone. The structures of the compounds were confirmed by spectroscopic data. The antifeedant activity of piperitone to Myzus persicae was studied, and the biological consequences of structural modifications of piperitone, that is, lactonization and chiral center configuration, were examined as well. The behavioral responses of M. persicae to piperitone and piperitone-derived saturated lactones were investigated to reveal the biological background of their deterrent activity. Piperitone appeared rather neutral or weakly deterrent to aphids. The introduction of a lactone moiety into a piperitone molecule dramatically changed its biological activity. All piperitone-derived lactones evoked negative aphid responses. However, the deterrent activity of individual compounds varied in potency, the time of expression, and the duration of the effect, depending on the spatial structure of the lactone. Lactones (1R,3S,6R)-3-isopropyl-6-methyl-9-oxabicyclo[4.3.0]nonan-8-one and trans-3-isopropyl-6-methyl-9-oxabicyclo[4.3.0]nonan-8-one showed the broadest ranges and the highest potencies and durabilities of deterrent activity to M. persicae: they acted immediately after application, caused a cessation of probing before aphids reached phloem elements, and decreased the quality of phloem sap. PMID:23477664

  12. Synthesis and in vitro Antimycobacterial Activity of Moxifloxacin Methylene and Ethylene Isatin Derivatives

    FENG Lian-shun; LIU Ming-liang; WANG Shuo; CHAI Yun; LI Su-jie; GUO Hui-yuan

    2012-01-01

    A series of novel moxifloxacin methylene and ethylene isatin derivatives with remarkable improvement in lipophilicity,compared to the parent moxifloxacin,was designed,synthesized and characterized by 1H NMR,MS and HRMS.These derivatives were initially evaluated for their in vitro antimycobacterial activity against M.smegmatis CMCC 93202.Compounds 3a-3f,5a,5f and 5j were chosen for the further evaluation of their in vitro activity against Mycobacterium tuberculosis(MTB) H37Rv ATCC 27294 and MDR-MTB 09710.All the target compounds[minimum inhibitory concentration(M1C):0.39->16 μg/mL] were far more active than rifampin(MIC:2.0->256 μg/mL),but less active than moxifloxacin(MIC:0.1-1.0 μg/mL) against the three tested strains.The most active compounds 3a and 3c were found to be 2-64 fold more potent than isoniazid and rifampin against M.smegmatis CMCC 93202,2 fold more potent than rifampin against MTB H37Rv ATCC 27294,and 16->64 fold more potent than ethambutol,isoniazid and rifampin against MDR-MTB 09710.

  13. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    Martinowich Keri

    2011-03-01

    Full Text Available Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark phase. Conclusion Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

  14. Chemical Signals of Synthetic Disaccharide Derivatives Dominate Rhamnolipids at Controlling Multiple Bacterial Activities.

    Singh, Nischal; Shetye, Gauri S; Zheng, Hewen; Sun, Jiayue; Luk, Yan-Yeung

    2016-01-01

    Microbes secrete molecules that modify their environment. Here, we demonstrate a class of synthetic disaccharide derivatives (DSDs) that mimics and dominates the activity of naturally secreted rhamnolipids by Pseudomonas aeruginosa. The DSDs exhibit the dual function of activating and inhibiting the swarming motility through a concentration-dependent activity reversal that is characteristic of signaling molecules. Whereas DSDs tethered with a saturated farnesyl group exhibit inhibition of both biofilm formation and swarming motility, with higher activities than rhamnolipids, a saturated farnesyl tethered with a sulfonate group only inhibits swarming motility but promote biofilm formation. These results identified important structural elements for controlling swarming motility, biofilm formation, and bacterial adhesion and suggest an effective chemical approach to control intertwined signaling processes that are important for biofilm formation and motilities. PMID:26511780

  15. Analysis of the antimicrobial activities of a chemokine-derived peptide (CDAP-4) on Pseudomonas aeruginosa

    Chemokines are key molecules involved in the control of leukocyte trafficking. Recently, a novel function as antimicrobial proteins has been described. CCL13 is the only member of the MCP chemokine subfamily displaying antimicrobial activity. To determine Key residues involved in its antimicrobial activity, CCL13 derived peptides were synthesized and tested against several bacterial strains, including Pseudomonas aeruginosa. One of these peptides, corresponding to the C-terminal region of CCL13 (CDAP-4) displayed good antimicrobial activity. Electron microscopy studies revealed remarkable morphological changes after CDAP-4 treatment. By computer modeling, CDAP-4 in α helical configuration generated a positive electrostatic potential that extended beyond the surface of the molecule. This feature is similar to other antimicrobial peptides. Altogether, these findings indicate that the antimicrobial activity was displayed by CCL13 resides to some extent at the C-terminal region. Furthermore, CDAP-4 could be considered a good antimicrobial candidate with a potential use against pathogens including P. aeruginosa

  16. Synthesis of Some Pyrazolone Derivatives and Evaluation of its Antibacterial and Cytotoxic Activity

    Rishiram Prajuli

    2015-12-01

    Full Text Available A series of novel pyrazolone derivative were synthesized by two different schemes (scheme-1 by the reaction of phenyl hydrazine and ethyl acetoacetate with substituted benzaldehydes PYR-1 to PYR-4 and (by the reaction of synthesized chalcone with phenyl hydrazine PYR-5 and characterised with its physical parameters (M.P, colour, %yield, solubility etc.. The entire synthesized compound was tested for their antimicrobial activity against Gram-positive and Gram-negative strains of bacteria and brimeshrimp bioassay was conducted for evaluation of cytotoxic activity The Investigation of antimicrobial screening data revealed that most of the tested compounds showed moderate to good antimicrobial activity. And cytotoxicity activity of compounds was also found to be satisfactory.

  17. Metal-based biologically active azoles and β-lactams derived from sulfa drugs.

    Ebrahimi, Hossein Pasha; Hadi, Jabbar S; Almayah, Abdulelah A; Bolandnazar, Zeinab; Swadi, Ali G; Ebrahimi, Amirpasha

    2016-03-01

    Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding

  18. QSAR and docking studies on capsazepine derivatives for immunomodulatory and anti-inflammatory activity.

    Aparna Shukla

    Full Text Available Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR model against target tumor necrosis factor-α (TNF-α was developed using multiple linear regression method (MLR with good internal prediction (r2 = 0.8779 and external prediction (r2pred = 0.5865 using Discovery Studio v3.5 (Accelrys, USA. The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-α. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug.

  19. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

    Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

    2016-01-01

    The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression. PMID:26700461

  20. Influence of Surface Seawater and Atmospheric Conditions on the Ccn Activity of Ocean-Derived Aerosol

    Quinn, P.; Bates, T. S.; Russell, L. M.; Frossard, A. A.; Keene, W. C.; Kieber, D. J.; Hakala, J. P.

    2012-12-01

    Ocean-derived aerosols are produced from direct injection into the atmosphere (primary production) and gas-to-particle conversion in the atmosphere (secondary production). These different production mechanisms result in a broad range of particle sizes that has implications for the impact of ocean-derived aerosol on climate. The chemical composition of ocean-derived aerosols is a result of a complex mixture of inorganic sea salt and organic matter including polysaccharides, proteins, amino acids, microorganisms and their fragments, and secondary oxidation products. Both production mechanisms and biological processes in the surface ocean impact the ability of ocean-derived aerosol to act as cloud condensation nuclei (CCN). In addition, CCN activity can be impacted by atmospheric processing that modifies particle size and composition after the aerosol is emitted from the ocean. To understand relationships between production mechanism, surface ocean biology, and atmospheric processing, measurements were made of surface ocean chlorophyll and dissolved organic matter; nascent sea spray aerosol freshly emitted from the ocean surface; and ambient marine aerosol. These measurements were made along the coast of California and in the North Atlantic between the northeast US and Bermuda. These regions include both eutrophic and oligotraphic waters and, thus, provide for observations over a wide range of ocean conditions.

  1. Antiadherent and Antibiofilm Activity of Humulus lupulus L. Derived Products: New Pharmacological Properties

    Marcin Rozalski

    2013-01-01

    Full Text Available New antimicrobial properties of products derived from Humulus lupulus L. such as antiadherent and antibiofilm activities were evaluated. The growth of gram-positive but not gram-negative bacteria was inhibited to different extents by these compounds. An extract of hop cones containing 51% xanthohumol was slightly less active against S. aureus strains (MIC range 31.2–125.0 μg/mL than pure xanthohumol (MIC range 15.6–62.5 μg/mL. The spent hop extract, free of xanthohumol, exhibited lower but still relevant activity (MIC range 1-2 mg/mL. There were positive coactions of hop cone, spent hop extracts, and xanthohumol with oxacillin against MSSA and with linezolid against MSSA and MRSA. Plant compounds in the culture medium at sub-MIC concentrations decreased the adhesion of Staphylococci to abiotic surfaces, which in turn caused inhibition of biofilm formation. The rate of mature biofilm eradication by these products was significant. The spent hop extract at MIC reduced biofilm viability by 42.8%, the hop cone extract by 74.8%, and pure xanthohumol by 86.5%. When the hop cone extract or xanthohumol concentration was increased, almost complete biofilm eradication was achieved (97–99%. This study reveals the potent antibiofilm activity of hop-derived compounds for the first time.

  2. Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities

    Dongwei Zhong

    2015-04-01

    Full Text Available Analogues or isosteres of α,γ-diketoacid (DKA 1a show potent inhibition of hepatitis C virus (HCV NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2 could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively. Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.

  3. Spectrum of activity and mechanisms of resistance of various nucleoside derivatives against gammaherpesviruses.

    Coen, Natacha; Duraffour, Sophie; Topalis, Dimitri; Snoeck, Robert; Andrei, Graciela

    2014-12-01

    The susceptibilities of gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and animal rhadinoviruses, to various nucleoside analogs was investigated in this work. Besides examining the antiviral activities and modes of action of antivirals currently marketed for the treatment of alpha- and/or betaherpesvirus infections (including acyclovir, ganciclovir, penciclovir, foscarnet, and brivudin), we also investigated the structure-activity relationship of various 5-substituted uridine and cytidine molecules. The antiviral efficacy of nucleoside derivatives bearing substitutions at the 5 position was decreased if the bromovinyl was replaced by chlorovinyl. 1-β-D-Arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), a nucleoside with an arabinose configuration of the sugar ring, exhibited no inhibitory effect against rhadinoviruses but was active against EBV. On the other hand, the fluoroarabinose cytidine analog 2'-fluoro-5-iodo-aracytosine (FIAC) showed high selectivity indices against gammaherpesviruses that were comparable to those of brivudin. Additionally, we selected brivudin- and acyclovir-resistant rhadinoviruses in vitro and characterized them by phenotypic and genotypic (i.e., sequencing of the viral thymidine kinase, protein kinase, and DNA polymerase) analysis. Here, we reveal key amino acids in these enzymes that play an important role in substrate recognition. Our data on drug susceptibility profiles of the different animal gammaherpesvirus mutants highlighted cross-resistance patterns and indicated that pyrimidine nucleoside derivatives are phosphorylated by the viral thymidine kinase and purine nucleosides are preferentially activated by the gammaherpesvirus protein kinase. PMID:25267682

  4. Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives

    Sinara Mônica Vitalino de Almeida

    2015-06-01

    Full Text Available In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z-2-(acridin-9-ylmethylene-N-phenylhydrazinecarbothioamide derivatives (3a–h were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 104 to 1.0 × 106 M−1 and quenching constants from −0.2 × 104 to 2.18 × 104 M−1 indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z-2-(acridin-9-ylmethylene-N- (4-chlorophenyl hydrazinecarbothioamide (3f, while the most active compound in antiproliferative assay was (Z-2-(acridin-9-ylmethylene-N-phenylhydrazinecarbothioamide (3a. There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

  5. Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives.

    de Almeida, Sinara Mônica Vitalino; Lafayette, Elizabeth Almeida; da Silva, Lúcia Patrícia Bezerra Gomes; Amorim, Cézar Augusto da Cruz; de Oliveira, Tiago Bento; Ruiz, Ana Lucia Tasca Gois; de Carvalho, João Ernesto; de Moura, Ricardo Olímpio; Beltrão, Eduardo Isidoro Carneiro; de Lima, Maria do Carmo Alves; de Carvalho Júnior, Luiz Bezerra

    2015-01-01

    In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a-h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 10(4) M(-1) indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties. PMID:26068233

  6. 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives: Synthesis and Antiproliferative Activity

    Guillermo Schmeda-Hirschmann

    2013-07-01

    Full Text Available Hybrid compounds are relevant products when searching for structure-activity relationships of natural products. Starting from the naturally occurring triterpene oleanolic acid, alkyl esters were prepared and treated with different aromatic azides using click chemistry to produce hybrid compounds. Some 18 new oleanolic acid derivatives were synthesized and the structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new derivatives was evaluated towards normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, promyelocytic leukemia (HL-60, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. The alkyne esters 1 and 3 showed activity on all cell lines but without selectivity (19.6–23.1 μM and 14.1–56.2 μM, respectively, their respective methyl esters were inactive. Compounds with a benzene and p-anisole attached to the triazole ring, showed no antiproliferative effect. Introduction of a chlorine atom into the benzene ring (compound 9 elicited a selective effect against AGS cells (IC50 value: 8.9 μM. The activity was lost when the COOH function at C-28 was methylated. Better antiproliferative effect was found for compounds 11 and 15 bearing a p-toluenesulphonyl group, with values in the range of 10.8–47.1 μM and 11.5–22.2 μM, respectively. The effect, however, was not associated with selectivity.

  7. Histamine modulates multiple functional activities of monocyte-derived dendritic cell subsets via histamine receptor 2.

    Simon, Tünde; Gogolák, Péter; Kis-Tóth, Katalin; Jelinek, Ivett; László, Valéria; Rajnavölgyi, Eva

    2012-02-01

    Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. The diverse biological effects of histamine are mediated by G-protein-coupled histamine receptors (HRs), which are able to modulate the functional activities of DC subsets. The goal of the present study was to compare the expression and activity of HRs in the CD1a(-) and CD1a(+) monocyte-derived DC subsets and to test the effects of histamine on the differentiation, activation and functional activities of these subsets. We show that H2R is present at high levels in both DC subsets, whereas H1R and H4R are expressed in a subset-specific manner. Histamine shifts DC differentiation to the development of CD1a(-) DCs and modulates DC activation through its inhibitory effect on CD1a(+) DC differentiation. Histamine-induced reduction of CD1a(+) DCs is associated with increased secretion of IL-6 and IL-10, up-regulation of a typical combination of chemokines, expression C5aR1 by the CD1a(-) DC subset and enhanced migration of both activated DC subsets supported by the production of MMP-9 and MMP-12 enzymes. All these effects were shown to be mediated in a H2R-specific manner as revealed by the specific antagonist of the receptor. As H2R is expressed at high levels in both DC subsets, we propose that it may dominate the regulation of multiple DC functions. In contrast, H1R and H4R with opposing subset-related expression may have a regulatory or fine-tuning role in histamine-induced functional activities. PMID:22232416

  8. Antibacterial activity of irradiated and non-irradiated chitosan and chitosan derivatives against Escherichia coli growth

    Samples of chitosan and four chitosan derivatives [ionic chitosan, chitosan lactate, carboxymethyl chitosan (C) and carboxymethyl chitosan (L)] were studied for their antibacterial activities against Escherichia coli growth. Chitosan and chitosan derivatives were prepared at concentrations 20, 100, 1000, 10000 ppm and 250, 1000, 5000, 10000, 20000 ppm, respectively. Each of the samples was tested before and after irradiation with electron beam at 25 kGy. The turbidity of bacterial growth media was measured periodically at 0, 0.5, 1, 2, 4, 6 and 24 h after inoculation using the optical density method. The results indicated that non- irradiated chitosan inhibited E. coli growth at 20 and 100 ppm. Meanwhile, irradiated chitosan at 100 and 1000 ppm concentration inhibited E. coli growth. Both irradiated and non-irradiated ionic chitosan inhibited E. coli growth at all concentrations used. Chitosan lactate was found to inhibit E. coli at concentration as low as 5000 ppm for both irradiated and non-irradiated samples. E. coli growth was not inhibited by carboxymethyl chitosan (C) and carboxymethyl chitosan (L), before and after irradiation. The findings suggested that chitosan has greater antibacterial activity as compared to the chitosan derivative samples. (Author)

  9. Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model

    Kaspar Emanuel Vogt

    2014-03-01

    Full Text Available Neurodevelopmental diseases such as the Rett syndrome have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2 gene (MeCP2-/y and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind Rett syndrome pathophysiology.

  10. Reduced synaptic activity in neuronal networks derived from embryonic stem cells of murine Rett syndrome model.

    Barth, Lydia; Sütterlin, Rosmarie; Nenniger, Markus; Vogt, Kaspar E

    2014-01-01

    Neurodevelopmental diseases such as the Rett syndrome (RTT) have received renewed attention, since the mechanisms involved may underlie a broad range of neuropsychiatric disorders such as schizophrenia and autism. In vertebrates early stages in the functional development of neurons and neuronal networks are difficult to study. Embryonic stem cell-derived neurons provide an easily accessible tool to investigate neuronal differentiation and early network formation. We used in vitro cultures of neurons derived from murine embryonic stem cells missing the methyl-CpG-binding protein 2 (MECP2) gene (MeCP2-/y) and from wild type cells of the corresponding background. Cultures were assessed using whole-cell patch-clamp electrophysiology and immunofluorescence. We studied the functional maturation of developing neurons and the activity of the synaptic connections they formed. Neurons exhibited minor differences in the developmental patterns for their intrinsic parameters, such as resting membrane potential and excitability; with the MeCP2-/y cells showing a slightly accelerated development, with shorter action potential half-widths at early stages. There was no difference in the early phase of synapse development, but as the cultures matured, significant deficits became apparent, particularly for inhibitory synaptic activity. MeCP2-/y embryonic stem cell-derived neuronal cultures show clear developmental deficits that match phenotypes observed in slice preparations and thus provide a compelling tool to further investigate the mechanisms behind RTT pathophysiology. PMID:24723848

  11. Design, synthesis, and herbicidal activity of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives.

    Xie, Yong; Chi, Hui-Wei; Guan, Ai-Ying; Liu, Chang-Ling; Ma, Hong-Juan; Cui, Dong-Liang

    2014-12-31

    A series of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives were designed and synthesized using 2-phenylpridines as the lead compound by intermediate derivatization methods in an attempt to obtain novel compound candidates for weed control. The herbicidal activity assay in glasshouse tests showed several compounds (II6, II7, II8, II9, II10, II11, III2, III3, III4, and III5) could efficiently control velvet leaf, youth-and-old age, barnyard grass, and foxtail at the 37.5 g/ha active substance. Especially, the activities of II6, II7, III2, and III4 were proved roughly equivalent to the saflufenacil and better than 95% sulcotrione at the same concentration. The result of the herbicidal activity assay in field tests demonstrated that II7 at 60 g/ha active substance could give the same effect as bentazon at 1440 g/ha active substance to control dayflower and nightshade, meanwhile II7 showed better activity than oxyfluorfen to control arrowhead and security to rice. The present work indicates that II7 may be a novel compound candidate for potential herbicide. PMID:25437124

  12. SYNTHESIZING DERIVATIVES FROM CYCLOPENTANONE ANALOGUE CURCUMIN AND THEIR TOXIC, ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES

    Adel Zamri1

    2011-11-01

    Full Text Available Three types of cyclopentanone derivatives have been synthesized from aromatic aldehyde and ketone derivatives undera base condition through aldol condensation. These cyclopentanone products were 2,5-dibenzylidene-cyclopentanone(a, 2,5-bis-(4-hydroxy-benzylidene-cyclopentanone (b, and 2,5-bis-(4-hydroxy-benzylidene-cyclopentanone (cwhich has a yield of 63-99%. The chemical structure of these compounds were determined using UV, IR and NMRspectroscopy. In order to clarify the role of hydroxyl and amine moieties, toxic, antioxidant and anti-inflammatoryactivities were carried out. The toxic test indicated that the compounds showed strong toxicity. In addition, the presenceof hydroxyl and amine groups on both rings of curcumin increased the antioxidant and anti-inflammatory activities

  13. Semisynthesis and Antifeedant Activity of New Derivatives of a Dihydro-β-Agarofuran from Parnassia wightiana

    Jun-Mian Tian

    2013-09-01

    Full Text Available Five new derivatives (2–6 were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 2–6 were confirmed by 1D- and 2D-NMR and HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (1–6 were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant effects of compounds 2 and 4 were greater than the parent compound 1 whereas other compounds exhibited low to no feeding deterrent effects against third instar M. separata larvae in lab bioassays. Therefore, our results suggest that acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve the antifeeding effect. This preliminary information will be useful in designing new insect control agents against M. separata and other important pests.

  14. Synthesis of 1-isopropyl-3-acyl-5-methyl-benzimidazolone Derivatives and Their Antimicrobial Activity

    Shaopeng Wei

    2013-03-01

    Full Text Available A series of N-acylated analogues of 1-isopropyl-3-acyl-5-methyl-benzimidazolone were synthesized. Bioassay results indicated that analogues 5-07 and 5-19 exhibited the most potency against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Analogues 5-02, 5-07, 5-12, 5-15, 5-19, 5-20 and 5-25 could effectively inhibit the spore germination of Botrytis cinerea. The relationship between structure and their antimicrobial activity (SAR has also been discussed according to aliphatic acids and aromatic acids derivatives, respectively. This implied that the N-acylated derivatives of 5-methyl-benzimidazolone might be potential antimicrobial agents.

  15. Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus

    Hui ZHANG; Lu ZHANG; Li-juan PENG; Xiao-wu DONG; Di WU; Vivian Chi-Hua WU; Feng-qin FENG

    2012-01-01

    Fatty acids and derivatives (FADs) are resources for natural antimicrobials.In order to screen for additional potent antimicrobial agents,the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay.Monoglycerides of fatty acids were the most potent class of fatty acids,among which monotridecanoin possessed the most potent antimicrobial activity.The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR:R2=0.942,Q2LOO=0.910; CoMFA:R2=0.979,Q2=0.588,respectively).Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structureactivity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents.

  16. Nomex-derived activated carbon fibers as electrode materials in carbon based supercapacitors

    Leitner, K.; Lerf, A.; Winter, M.; Besenhard, J. O.; Villar-Rodil, S.; Suárez-García, F.; Martínez-Alonso, A.; Tascón, J. M. D.

    Electrochemical characterization has been carried out for electrodes prepared of several activated carbon fiber samples derived from poly (m-phenylene isophthalamide) (Nomex) in an aqueous solution. Depending on the burn-off due to activation the BET surface area of the carbons was in the order of 1300-2800 m 2 g -1, providing an extensive network of micropores. Their capability as active material for supercapacitors was evaluated by using cyclic voltammetry and impedance spectroscopy. Values for the capacitance of 175 F g -1 in sulfuric acid were obtained. Further on, it was observed that the specific capacitance and the performance of the electrode increase significantly with increasing burn-off degree. We believe that this fact can be attributed to the increase of surface area and porosity with increasing burn-off.

  17. Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives.

    Kumar, Sujeet; Gopalakrishnan, Vidya; Hegde, Mahesh; Rana, Vivek; Dhepe, Sharad S; Ramareddy, Sureshbabu A; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Srivastava, Mrinal; Raghavan, Sathees C; Karki, Subhas S

    2014-10-01

    A series of 2,5,6-substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives have been prepared and were tested for antiproliferative activity on cancer cells at the National Cancer Institute. Results showed that molecules with a benzyl group at position 2, exhibited an increase in activity for the introduction of a formyl group at the 5 position. The compound 2-benzyl-5-formyl-6-(4-bromophenyl)imidazo[2,1-b][1,3,4]thiadiazole 22 has been chosen for understanding the mechanism of action by various molecular and cellular biology studies. Results obtained from cell cycle evaluation analysis, analysis of mitochondrial membrane potential and Annexin V-FITC by flow cytometric analysis, ROS production and expression of apoptotic and DNA-repair proteins suggested that compound 22 induced cytotoxicity by activating extrinsic pathway of apoptosis, however, without affecting cell cycle progression. PMID:25205189

  18. AN INVESTIGATION OF MUTAGENIC ACTIVITIES OF SOME 9- SUBSTITUEDPHENANTHRENE DERIVATIVES WITH AMES / SALMONELLA / MICROSOME TEST

    Mehtap KUTLU

    2011-02-01

    Full Text Available In this study, three different 9-Substituted phenantrene derivatives that were synthesized to be used as basic matter for drugs were tested for their mutagenic potency in strains TA 98 and TA 100 ofSalmonella typhimurium by using Ames test. Therefore, both strains were tested in the absence or presence of S9 metabolic activation, for five different doses of each test substances in two paralel independent experiments. In the absence of metabolic activation, while only one of the compounds were causing frame-shift mutations, two of them were determined to induce base pair substitution mutations. In the presence of metabolic activation, while two of the compounds were mutagenic for TA 98, base pair substitution mutations were not detected for any of the substances. Each of the compoundstested were found to be mutagenic for at least one strain in the presence or absence of S9.

  19. Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

    Borgati, Thiago F.; Alves, Rosemeire B., E-mail: thfborgati@gmail.com, E-mail: rosebrondi@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Quimica; Teixeira, Robson R.; Freitas, Rossimiriam P. de; Perdigao, Thays G.; Silva, Silma F. da; Santos, Aline Aparecida dos [Universidade Federal de Vicosa, MG (Brazil). Departamento de Quimica; Bastidas, Alberto de Jesus O. [Laboratorio de Quimica Ecologica, Departamento de Quimica, Universidad de Los Andes, Nucleo Universitario Pedro Rincon Gutierrez, Merida (Viet Nam)

    2013-06-15

    Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10{sup -4} mol L{sup -1}. Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

  20. N-(4-((E)-3-arylacryloyl)phenyl)acetamide derivatives and their antileishmanial activity

    The antileishmanial activity of a series of enonic derivatives (chalcones) synthesized via Claisen-Schmidt condensation reactions assisted by ultrasonic radiation was characterized by analyzing their cytotoxicity against Leishmania (Viannia) panamensis promastigotes, a species responsible for over 90% of Leishmania cases in Colombia. Two compounds were active against Leishmania with selectivity indexes of LC50 EC50-1 (lethal concentration 50 and effective concentration 50) higher than 27 and 3, respectively. These results suggest that a substitution on one of the two chalcone rings (aromatic ring A) with oxygen is convenient. Compound 3g should be further investigated for its antileishmanial activity, especially for being easy to obtain in high yields, making it possible to produce drugs for the treatment of cutaneous leishmaniasis. (author)

  1. N-(4-((E)-3-arylacryloyl)phenyl)acetamide derivatives and their antileishmanial activity

    Pacheco, Dency J.; Trilleras, Jorge; Prent, Luis; Coaves, Tobinson, E-mail: jorgetrilleras@mail.uniatlantico.edu.co [Universidad del Atlantico, Barranquilla-Atlantico (Colombia). Facultad de Ciencias Basicas. Grupo de Investigacion en Compuestos Heterociclicos; Quiroga, Jairo [Universidad del Valle, Cali (Colombia). Dept. de Quimica. Grupo de Investigacion de Compuestos Heterociclicos; Gutierrez, Jennifer; Delgado, Gabriela [Universidad Nacional de Colombia, Bogota, D.C. (Colombia). Facultad de Ciencias. Departamento de Farmacia. Grupo de Investigacion en Inmunotoxicologia; Marin, Juan C. [Universidad Nacional de Colombia, Bogota, D.C. (Colombia). Facultad de Ciencias. Departamento de Farmacia. Grupo de Investigacion Farmacognosia y Fitoquimica

    2013-10-15

    The antileishmanial activity of a series of enonic derivatives (chalcones) synthesized via Claisen-Schmidt condensation reactions assisted by ultrasonic radiation was characterized by analyzing their cytotoxicity against Leishmania (Viannia) panamensis promastigotes, a species responsible for over 90% of Leishmania cases in Colombia. Two compounds were active against Leishmania with selectivity indexes of LC{sub 50} EC{sub 50} {sup -1} (lethal concentration 50 and effective concentration 50) higher than 27 and 3, respectively. These results suggest that a substitution on one of the two chalcone rings (aromatic ring A) with oxygen is convenient. Compound 3g should be further investigated for its antileishmanial activity, especially for being easy to obtain in high yields, making it possible to produce drugs for the treatment of cutaneous leishmaniasis. (author)

  2. Synthesis, Antimicrobial and Antitubercular Activities of Some Novel Carboxamide Derivatives of 2-Quinolones

    Abhishek Kumar

    2014-12-01

    Full Text Available A series of novel substituted N-(3-acetyl-2-oxoquinolin-1(2H-ylbenzamide (AJQC1-AJQC12 have been synthesized upon refluxing 3-acetyl-1-amino-quinolin-2-one and substituted benzoic acid in the presence of dry redistilled pyridine and silicon tetra chloride as coupling agent. 3-acetyl-1-amino-quinolin-2-one (AJQ1-AJQ12 were synthesized from substituted 3-acetyl coumarin upon refluxing with hydrazine hydrate and ethanol. The structures of the final carboxamide derivatives were confirmed by IR, 1H NMR and mass spectra. The synthesized compounds were screened for their antimicrobial activity by tube dilution method and anti tubercular activity by microplate Alamar blue assay. Most of the compounds have exhibited promising antibacterial, anti fungal and anti tubercular activities.

  3. Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

    Zhang, Xiang; Geo, Yongxin; Liu, Huijun; Guo, Baoyuan; Wang, Huili [Research Center for Eco-Environmental Sciences/Chinese Academy of Sciences, Beijing (China)

    2012-04-15

    Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, {sup 1}H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin.

  4. Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

    Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, 1H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin

  5. Multispectral studies of DNA binding, antioxidant and cytotoxic activities of a new pyranochromene derivative

    Dehkordi, Mahvash Farajzadeh; Dehghan, Gholamreza; Mahdavi, Majid; Hosseinpour Feizi, Mohammad Ali

    2015-06-01

    The binding properties of a new pyranochromene derivative, 2-amino-4-(3-hydroxyphenyl)-5-oxo-4H, 5H-pyrano-[3, 2-c] chromene-3-carbonitrile (3-HC) with calf thymus DNA (ctDNA) have been investigated by UV-vis absorption, circular dichroism, fluorescence spectroscopy and viscosity measurement. These results indicated that 3-HC can interact with DNA through non-intercalative mode and the intrinsic binding constant (Kb) for 3-HC with DNA was estimated to be 3.6 × 103 M-1. The antioxidant activity experiments show that 3-HC also exhibit good antioxidant activity in DPPH free radical scavenging and ferric reducing ability methods. Moreover, 3-HC exhibited cytotoxic activity against K562, human chronic myelogenous leukemia cells, with IC50 value of 146 μM and the cells responded to the treatment with mostly through apoptosis.

  6. Synthesis, antifeedant activity against Coleoptera and 3D QSAR study of alpha-asarone derivatives.

    Łozowicka, B; Kaczyński, P; Magdziarz, T; Dubis, A T

    2014-01-01

    For the first time, a set of 56 compounds representing structural derivatives of naturally occurring alpha-asarone as an antifeedants against stored product pests Sitophilus granarius L., Trogoderma granarium Ev., and Tribolium confusum Duv., were subjected to the 3D QSAR studies. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for 56 compounds, including 15 newly synthesized, were performed using comparative molecular field analysis s-CoMFA and SOM-CoMSA techniques. QSAR was conducted based on a combination of biological activity (against Coleoptera larvae and beetles) and various geometrical, topological, quantum-mechanical, electronic, and chromatographic descriptors. The CoMSA formalism coupled with IVE (CoMSA-IVE) allowed us to obtain highly predictive models for Trogoderma granarium Ev. larvae. We have found that this novel method indicates a clear molecular basis for activity and lipophilicity. This investigation will facilitate optimization of the design of new potential antifeedants. PMID:24601760

  7. Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

    Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10-4 mol L-1. Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

  8. Synthesis of isatin thiosemicarbazones derivatives: In vitro anti-cancer, DNA binding and cleavage activities

    Ali, Amna Qasem; Teoh, Siang Guan; Salhin, Abdussalam; Eltayeb, Naser Eltaher; Khadeer Ahamed, Mohamed B.; Majid, A. M. S. Abdul

    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (kb = 5.03-33.00 × 105 M-1) for L1-L3 and L5 and (6.14-9.47 × 104 M-1) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.

  9. Regioselective synthesis, characterization, and antimicrobial activities of some new monosaccharide derivatives.

    Kawsar, Sarkar M A; Faruk, Md O; Rahman, Mohammad S; Fujii, Yuki; Ozeki, Yasuhiro

    2014-03-01

    A regioselective acylation series of methyl α-D-glucopyranoside (1), methyl 3-O-benzoyl-4,6-O-benzylidene-α-D-mannopyranoside (1A), and methyl 4,6-O-benzylidene-2-O-(3,5-dinitrobenzoyl)-α-D-mannopyranoside (1B) has been carried out by the direct acylation method and afforded the 2,6-di-O-glucopyranoside and 2 or 3-O-mannopyranoside derivatives in an excellent yield. In order to obtain newer products, the 2,6-di-O-glucopyranoside derivative was further transformed to a series of 3,4-di-O-acyl derivatives containing a wide variety of functionalities in a single molecular framework. The structures of the newly synthesized compounds were elucidated on the basis of IR, (1)H-NMR, (13)C-NMR, (13)C-DEPT spectral data, and elemental analysis. These synthesized derivatives were screened for in vitro antimicrobial activities against ten human pathogenic and five phytopathogenic microorganisms. A number of test compounds showed remarkable antimicrobial activity comparable to, and in some cases even higher than, the standard antibiotics employed. It was observed that methyl 3,4-di-O-(3-chlorobenzoyl)-2,6-di-O-hexanoyl-α-D-glucopyranoside (8) exhibited a varied range of MIC from 12.5 μg/disc to 25 μg/disc by the disk diffusion method and 1000 μg/mL to 1250 μg/mL by the broth macrodilution method. PMID:24634838

  10. Anti-cancer efficacy of silybin derivatives -- a structure-activity relationship.

    Chapla Agarwal

    Full Text Available Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that potency of silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of silybin derivatives namely 2,3-dehydrosilybin (DHS, 7-O-methylsilybin (7OM, 7-O-galloylsilybin (7OG, 7,23-disulphatesilybin (DSS, 7-O-palmitoylsilybin (7OP, and 23-O-palmitoylsilybin (23OP; and compared their anti-cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to silybin, while other silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy. Isomers of these three silybin derivatives also showed better efficacy compared with respective silybin isomers, but in each, there was no clear cut silybin A versus B isomer activity preference. Further studies in HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall, these results clearly suggest that the anti-cancer efficacy of silybin could be significantly enhanced through structural modifications, and identify strong anti-cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical cancer models in rodents.

  11. Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety

    Mohammadhosseini Negar

    2012-08-01

    Full Text Available Abstract Background and the purpose of the study Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities. Methods The N-substituted analogs of levofloxacin 6a–j were prepared by nucleophilic reaction of N-desmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria. Results All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC = 0.04-6.25 μg/mL; however, the activity against Gram-negative bacteria was lower (MIC = 1.56–100 μg/mL. As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC = 0.04–0.19 μg/mL, and their activities were found to be 5–25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4. Conclusion We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive

  12. Synthesis, antifungal activity, and QSAR studies of 1,6-dihydropyrimidine derivatives

    Chirag Rami

    2013-01-01

    Full Text Available Introduction: A practical synthesis of pyrimidinone would be very helpful for chemists because pyrimidinone is found in many bioactive natural products and exhibits a wide range of biological properties. The biological significance of pyrimidine derivatives has led us to the synthesis of substituted pyrimidine. Materials and Methods: With the aim of developing potential antimicrobials, new series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine derivatives namely 2-(5-cyano-6-oxo-4-substituted (aryl-1,6-dihydropyrimidin-2-ylthio-N-substituted (phenyl acetamide (C1-C41 were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR, mass analysis, and proton nuclear magnetic resonance ( 1 H NMR. All the compounds were screened for their antifungal activity against Candida albicans (MTCC, 227. Results and Discussion: Quantitative structure activity relationship (QSAR studies of a series of 1,6-dihydro-pyrimidine were carried out to study various structural requirements for fungal inhibition. Various lipophilic, electronic, geometric, and spatial descriptors were correlated with antifungal activity using genetic function approximation. Developed models were found predictive as indicated by their square of predictive regression values (r 2pred and their internal and external cross-validation. Study reveals that CHI_3_C, Molecular_SurfaceArea, and Jurs_DPSA_1 contributed significantly to the activity along with some electronic, geometric, and quantum mechanical descriptors. Conclusion: A careful analysis of the antifungal activity data of synthesized compounds revealed that electron withdrawing substitution on N-phenyl acetamide ring of 1,6-dihydropyrimidine moiety possess good activity.

  13. Synthesis, cytotoxicity, and antiplasmodial and antitrypanosomal activity of new neocryptolepine derivatives.

    Jonckers, Tim H M; van Miert, Sabine; Cimanga, Kanyanga; Bailly, Christian; Colson, Pierre; De Pauw-Gillet, Marie-Claire; van den Heuvel, Hilde; Claeys, Magda; Lemière, Filip; Esmans, Eddy L; Rozenski, Jef; Quirijnen, Ludo; Maes, Louis; Dommisse, Roger; Lemière, Guy L F; Vlietinck, Arnold; Pieters, Luc

    2002-08-01

    On the basis of the original lead neocryptolepine or 5-methyl-5H-indolo[2,3-b]quinoline, an alkaloid from Cryptolepis sanguinolenta, derivatives were prepared using a biradical cyclization methodology. Starting from easily accessible educts, this approach allowed the synthesis of hitherto unknown compounds with a varied substitution pattern. As a result of steric hindrance, preferential formation of the 3-substituted isomers over the 1-substituted isomers was observed when cyclizing N-(3-substituted-phenyl)-N'-[2-(2-trimethylsilylethynyl)phenyl]carbodiimides. All compounds were evaluated for their activity against chloroquine-sensitive as well as chloroquine-resistant Plasmodium falciparum strains, for their activity against Trypanosoma brucei and T. cruzi, and for their cytotoxicity on human MRC-5 cells. Mechanisms of action were investigated by testing heme complexation using ESI-MS, inhibition of beta-hematin formation, DNA interactions (DNA-methyl green assay and linear dichroism), and inhibition of human topoisomerase II. Neocryptolepine derivatives with a higher antiplasmodial activity and a lower cytotoxicity than the original lead have been obtained. This selective antiplasmodial activity was associated with inhibition of beta-hematin formation. 2-Bromoneocryptolepine was the most selective compound with an IC(50) value against chloroquine-resistant P. falciparum of 4.0 microM in the absence of cytotoxicity (IC(50) > 32 microM). Although cryptolepine, a known lead for antimalarials also originally isolated from Cryptolepis sanguinolenta, was more active (IC(50) = 2.0 microM), 2-bromoneocryptolepine showed a low affinity for DNA and no inhibition of human topoisomerase II, in contrast to cryptolepine. Although some neocryptolepine derivatives showed a higher antiplasmodial activity than 2-bromocryptolepine, these compounds also showed a higher affinity for DNA and/or a more pronounced cytotoxicity. Therefore, 2-bromoneocryptolepine is considered as the most

  14. Parameterizing ice nucleation rates using contact angle and activation energy derived from laboratory data

    J.-P. Chen

    2008-12-01

    Full Text Available The rate of ice nucleation in clouds is not easily determined and large discrepancies exist between model predictions and actual ice crystal concentration measured in clouds. In an effort to improve the parameterization of ice nucleating in cloud models, we investigate the rate of heterogeneous ice nucleation under specific ambient conditions by knowing the sizes as well as two thermodynamic parameters of the ice nuclei – contact angle and activation energy. Laboratory data of freezing and deposition nucleation modes were analyzed to derive inversely the two thermodynamic parameters for a variety of ice nuclei, including mineral dusts, bacteria, pollens, and soot particles. The analysis considered the Zeldovich factor for the adjustment of ice germ formation, as well as the solute and curvature effects on surface tension; the latter effects have strong influence on the contact angle. Contact angle turns out to be a more important factor than the activation energy in discriminating the nucleation capabilities of various ice nuclei species. By extracting these thermodynamic parameters, laboratory results can be converted into a formulation that follows classical nucleation theory, which then has the flexibility of incorporating factors such as the solute effect and curvature effect that were not considered in the experiments. Due to various uncertainties, contact angle and activation energy derived in this study should be regarded as "apparent" thermodynamics parameters.

  15. Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

    Mariano Walter Pertino

    2014-02-01

    Full Text Available Dehydroabietic acid (DHA is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid, and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol, four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

  16. Importance of being Nernst: Synaptic activity andfunctional relevance in stem cell-derived neurons

    2015-01-01

    Functional synaptogenesis and network emergence aresignature endpoints of neurogenesis. These behaviorsprovide higher-order confirmation that biochemicaland cellular processes necessary for neurotransmitterrelease, post-synaptic detection and network propagation of neuronal activity have been properly expressed andcoordinated among cells. The development of synapticneurotransmission can therefore be considered a definingproperty of neurons. Although dissociated primaryneuron cultures readily form functioning synapsesand network behaviors in vitro , continuously culturedneurogenic cell lines have historically failed to meet thesecriteria. Therefore, in vitro -derived neuron models thatdevelop synaptic transmission are critically needed for awide array of studies, including molecular neuroscience,developmental neurogenesis, disease research andneurotoxicology. Over the last decade, neurons derivedfrom various stem cell lines have shown varying ability todevelop into functionally mature neurons. In this review,we will discuss the neurogenic potential of various stemcells populations, addressing strengths and weaknessesof each, with particular attention to the emergenceof functional behaviors. We will propose methods tofunctionally characterize new stem cell-derived neuron(SCN) platforms to improve their reliability as physiologicalrelevant models. Finally, we will review howsynaptically active SCNs can be applied to accelerateresearch in a variety of areas. Ultimately, emphasizingthe critical importance of synaptic activity and networkresponses as a marker of neuronal maturation is anticipatedto result in in vitro findings that better translateto efficacious clinical treatments.

  17. Design, synthesis, and local anti-inflammatory activity of 17β-carboxamide derivatives of glucocorticoids.

    Dobričić, Vladimir; Marković, Bojan; Milenković, Nikola; Savić, Vladimir; Jaćević, Vesna; Rančić, Nemanja; Vladimirov, Sote; Cudina, Olivera

    2014-11-01

    Molecular docking studies were performed on 18 17β-carboxamide steroids in order to select compounds with potential local anti-inflammatory activity. These derivatives are amides of cortienic acids (obtained from hydrocortisone, prednisolone, and methylprednisolone) with methyl or ethyl esters of six amino acids. Interactions with the glucocorticoid receptor (GR), binding energies and ligand efficiency values of these compounds were compared with dexamethasone and cortienic acid obtained from prednisolone (inactive metabolite). On the basis of molecular docking studies, seven compounds were selected and their binding affinities for the GR were predicted by use of the exponential model created in this study. Subsequently, selected compounds were synthesized in good yields by use of modified N,N'-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) coupling procedure. Finally, the local anti-inflammatory activity of the synthesized compounds was examined by use of the croton oil-induced ear edema test. In vivo evaluation of systemic side effects as well as in silico prediction of metabolism were performed on the derivative with the best local anti-inflammatory activity. The combination of molecular docking studies and the exponential model for the GR binding affinity prediction could be used as an in silico tool for the rational design of novel 17β-carboxamide steroids with potentially better biological profile than dexamethasone. PMID:25159891

  18. Synthesis of benzamide derivatives of anacardic acid and their cytotoxic activity.

    Chandregowda, Venkateshappa; Kush, Anil; Reddy, Goukanapalli Chandrasekara

    2009-06-01

    Several benzamide derivatives were synthesized from anacardic acid (1a) which was the product of hydrogenation of the naturally occurring anacardic acid mixture (1a-d), a major constituent of cashew nut shell liquid. Anacardic acid (1a) was first alkylated followed by hydrolysis of the ester to obtain synthones namely, 2-ethoxy-6-pentadecylbenzoic acid (5) and 2-isopropoxy-6-pentadecylbenzoic acid (6). These salicylic acid derivatives were then coupled with a variety of anilines to obtain novel benzamide compounds (7-39). Cytotoxic effect of these synthesized compounds was tested on HeLa cell line of wild type with relatively high expression of p300 and on HCT-15, which is p300 negative. Of all the compounds, 2-isopropoxy-6-pentadecyl-N-pyridin-4-ylbenzamide (27), 2-ethoxy-N-(3-nitrophenyl)-6-pentadecylbenzamide (22) and 2-ethoxy-6-pentadecyl-N-pyridin-4-ylbenzamide (10) were found to be more potent with the respective IC(50) values 11.02 microM, 13.55 microM, 15.29 microM on HeLa cell line. Their activities are comparable with garcinol which is a cell permeable histone acetyltransferase (HAT) inhibitor and 10 fold more active than p300 HAT activators so far reported. PMID:19246131

  19. Antileishmanial and antitrypanosomal activity of triterpene derivatives from latex of two Euphorbia species.

    Mazoir, Noureddine; Benharref, Ahmed; Bailén, María; Reina, Matías; González-Coloma, Azucena; Martínez-Díaz, Rafael A

    2011-01-01

    The in vitro activity on Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes of 25 semisynthetic terpenoid derivatives has been evaluated. These compounds were obtained through chemical modifications of the major components of Euphorbia resinifera (alpha-euphol and alpha-euphorbol) and Euphorbia officinarum (obtusifoliol and 31-norlanosterol). Leishmaniasis and Chagas' disease are major worldwide health problems. The drugs of choice for their treatment are still problematic in both cases, and therefore there is an urgent need to discover new drugs with high activity and low side effects. Natural products have become a key source of new drugs in the last years. The genus Euphorbia has been the subject of abundant phytochemical and pharmacological research because of its potential medical applications, but the antiparasitic effects of derivatives from plants of this genus are still unknown. Our results showed that 76% and 64% of the test compounds had antiparasitic effects on L. infantum and T cruzi, respectively. The different activities on both parasites, especially their moderate effects on mammalian cells, indicate an interesting selective toxicity. PMID:21950160

  20. Plant-Derived Polyphenols Interact with Staphylococcal Enterotoxin A and Inhibit Toxin Activity

    Shimamura, Yuko; Aoki, Natsumi; Sugiyama, Yuka; Tanaka, Takashi; Murata, Masatsune; Masuda, Shuichi

    2016-01-01

    This study was performed to investigate the inhibitory effects of 16 different plant-derived polyphenols on the toxicity of staphylococcal enterotoxin A (SEA). Plant-derived polyphenols were incubated with the cultured Staphylococcus aureus C-29 to investigate the effects of these samples on SEA produced from C-29 using Western blot analysis. Twelve polyphenols (0.1–0.5 mg/mL) inhibited the interaction between the anti-SEA antibody and SEA. We examined whether the polyphenols could directly interact with SEA after incubation of these test samples with SEA. As a result, 8 polyphenols (0.25 mg/mL) significantly decreased SEA protein levels. In addition, the polyphenols that interacted with SEA inactivated the toxin activity of splenocyte proliferation induced by SEA. Polyphenols that exerted inhibitory effects on SEA toxic activity had a tendency to interact with SEA. In particular, polyphenol compounds with 1 or 2 hexahydroxydiphenoyl groups and/or a galloyl group, such as eugeniin, castalagin, punicalagin, pedunculagin, corilagin and geraniin, strongly interacted with SEA and inhibited toxin activity at a low concentration. These polyphenols may be used to prevent S. aureus infection and staphylococcal food poisoning. PMID:27272505

  1. Spectral Characterization and Antimicrobial Activity of Some Schiff Bases Derived from 4-Chloro-2-aminophenol and Various Salicylaldehyde Derivatives%Spectral Characterization and Antimicrobial Activity of Some Schiff Bases Derived from 4-Chloro-2-aminophenol and Various Salicylaldehyde Derivatives

    Cinarli, Adem; Gurbuz, Demet; Tavman, Aydin; Birteksoz, A. Seher

    2012-01-01

    A series of N-(5-chloro-2-hydroxyphenyl)-(3/4/5-substituted)-salicylaldimines (I--XI) were synthesized using appropriate synthetic route. Their structures were characterized by FT-IR, UV-Visible, ESI-MS, 1H and 13C NMR spectroscopic techniques and analytical methods. The crystal structure of N-(5-chloro-2-hydroxyphenyl)-5-bromo- salicylaldimine (V) was determined by X-ray diffraction at room temperature. Relationship between the melting points and the structures of the compounds was examined. Antimicrobial activity of the compounds was evaluated against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis. Antifungal activities were reported for Candida albicans. Schiff bases showed considerable antimicrobial activity against S. aureus, S, epidermidis and C. albicans. N-(5-Chloro-2-hydroxyphenyl)-3-hydroxy-salieylaldimine (II) has the broadest and highest antimicrobial activity according to the others.

  2. Synthesis and antibacterial activity studies of 6-methoxyquinazoline-triazole hybrid derivatives

    Venkataramireddy Veeramreddy

    2015-12-01

    Full Text Available The Click reaction between the electronically divergent triazole compounds 4-((l-(4-(tert-butylbenzyl-1H-l,2,3-triazol-4-ylmethoxy-5-methoxy-2-nitrobenzamides (8a-e with different aldehydes using Na 2S 2O 4 in DMSO was performed to obtain hybrid of quinazolinone-triazole derivatives (10a-o. All the synthesized compounds were fully characterized on the basis of their detailed spectral studies and screened for their antibacterial activities strains using paper disc method. The compounds (10 a-o were evaluated for their antibacterial activity against human pathogenic organism Escherichia Coli, Staphylococcus aureus (Table 1. The investigation of antibacterial screening data reveal that 10e, 10f, 10g, 10j and 10n were highly active against E. coli, where as 10b, 10d, 10j,10k and 10o showed least activity. Compounds 10b, 10e, 10f, 10g, 10i, 10k and 10n showed high activity against S. aureus, where as compounds 10d, 10j, 10o showed least activity. Compounds 10c, 10h, 10l and 10o were inactive against both organisms employed.

  3. Synthesis and antioxidant evaluation of isochroman-derivatives of hydroxytyrosol: structure-activity relationship.

    Mateos, Raquel; Madrona, Andrés; Pereira-Caro, Gema; Domínguez, Vanessa; Cert, Rosa M A; Parrado, Juan; Sarriá, Beatriz; Bravo, Laura; Espartero, José Luis

    2015-04-15

    Isochroman-derivatives of the natural olive oil phenol hydroxytyrosol (HT) have been synthesised via Oxa-Pictet-Spengler reaction in high yields. Lipophilicity and antioxidant activity were determined to establish the structure-activity relationship of isochromans compared to HT, BHT and α-tocopherol. Antioxidant capacity was tested in two different media: bulk oils, using the Rancimat test, and brain homogenates, by measuring malondialdehyde (MDA) levels as a lipoperoxidation biomarker. In addition, other antioxidant assays (FRAP, ABTS and ORAC) were carried out. Rancimat and MDA results show that antioxidant activity was related with lipophilicity, directly in brain homogenates and inversely in the oils, in agreement with the polar paradox. Free o-diphenolic groups positively determined the activity in the oils, whereas reducing and radical-scavenging activities were related to the number of free hydroxyl moieties. BHT and α-tocopherol showed lower antioxidant activity than isochromans and HT. We conclude that HT-isochromans present significant potential as bioactive compounds. PMID:25466028

  4. Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity.

    Sang-Ngern, Mayuramas; Youn, Ui Joung; Park, Eun-Jung; Kondratyuk, Tamara P; Simmons, Charles J; Wall, Marisa M; Ruf, Michael; Lorch, Sam E; Leong, Ethyn; Pezzuto, John M; Chang, Leng Chee

    2016-06-15

    Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8μM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6μM. PMID:27210437

  5. Acaricidal activities of materials derived from Pyrus ussuriensis fruits against stored food mites.

    Jeon, Ju-Hyun; Yang, Ji-Yeon; Lee, Hoi-Seon

    2012-07-01

    The acaricidal activities of materials derived from Pyrus ussuriensis fruits were evaluated against Tyrophagus putrescentiae and compared with that of commercial acaricide (benzyl benzoate). On the basis of the 50 % lethal dose (LD(50)) values, the ethyl acetate fraction of the fractions obtained from an aqueous extract of P. ussuriensis fruits had the highest acaricidal activity (16.32 μg/cm(2)) against T. putrescentiae. The acaricidal constituent of P. ussuriensis fruits was isolated by chromatographic techniques and identified as 1,4-benzoquinone. On the basis of the LD(50) values, 1,4-benzoquinone (1.98 μg/cm(2)) was 5.9 times more toxic than benzyl benzoate (11.69 μg/cm(2)), followed by 2-isopropyl-5-methyl-1,4-benzoquinone (3.29 μg/cm(2)), and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (5.03 μg/cm(2)) against T. putrescentiae in the fumigant bioassay. In a filter paper bioassay, the acaricidal activity of 1,4-benzoquinone (0.07 μg/cm(2)) was 120.1 times more effective than that of benzyl benzoate (8.41 μg/cm(2)), followed by 2-isopropyl-5-methyl-1,4-benzoquinone (0.11 μg/cm(2)) and 2,3-dimethoxy-5-methyl-1,4-benzoquinone (0.30 μg/cm(2)) against T. putrescentiae. These results demonstrate that P. ussuriensis fruit-derived material and its derivatives have potential as new preventive agents for the control of stored food mites. PMID:22980009

  6. Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line

    TOYOHARA, YUKIYO; HASHITANI, SUSUMU; Kishimoto, Hiromitsu; Noguchi, Kazuma; Yamamoto, Nobuto; Urade, Masahiro

    2011-01-01

    This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately...

  7. Synthesis and Antiplatelet Aggregation Activity Evaluation of some 2-Aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine Derivatives

    Esfahanizadeh, Marjan; Mohebbi, Shohreh; Dasht Bozorg, Behnam; Amidi, Salimeh; Gudarzi, Ali; Ayatollahi, Seyed Abdolmajid; Kobarfard, Farzad

    2015-01-01

    A series of novel 2-aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma using light transmission aggregometry. Among the tested derivatives, compounds Ia, Ib, IB and II16 exhibited the highest antiplatelet aggregation activity (36.75, 72.4, 62.5 and 80 µM). None of the compounds showed satisfactory activity against the ...

  8. Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity

    Chunli Liu; Ce Shi; Fei Mao; Yong Xu; Jinyan Liu; Bing Wei; Jin Zhu; Mingjie Xiang; Jian Li

    2014-01-01

    A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effect...

  9. N-Hydroxycinnamide Derivatives of Osthole Ameliorate Hyperglycemia through Activation of AMPK and p38 MAPK

    Wei-Hwa Lee

    2015-03-01

    Full Text Available Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4 translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the

  10. N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through activation of AMPK and p38 MAPK.

    Lee, Wei-Hwa; Wu, Hsueh-Hsia; Huang, Wei-Jan; Li, Yi-Ning; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

    2015-01-01

    Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor

  11. Synthesis and Pharmacological Activities of N-(3-HydroxyphenylBenzamide and its 3-O-Derivatives

    M. A. Abbasi

    2014-03-01

    Full Text Available N-(3-hydroxyphenyl benzamide (3 was synthesized by the condensation of 3-hydroxyaniline (1 with benzoyl chloride (2 in aqueous medium. From this parent molecule 3, various 3-O-derivatives, 5a-f, were prepared via O-alkylation, by reacting it with different alkyl halides, 4a-f, for 2 h under reflux conditions in the presence of mixture of Na-ethoxide and C2H5OH as solvent. The synthesized compounds were characterized by using different spectroscopic techniques and were subjected to enzyme inhibition activity against butylcholinesterase, acetylcholinesterase, and lipoxygenase enzymes.

  12. Synthesis and CDK2 kinase inhibitory activity of 7/7′-azaindirubin derivatives

    2010-01-01

    A series of novel 7'-azaindirubin(1a-g) and 7-azaindirubin(2a,2c,2e and 2f) derivatives were designed and synthesized.Their structures were characterized by ~1H NMR and MS spectroscopy as well as by elemental analysis.Their inhibitory properties against CDK2/cylinA were evaluated in vitro.In contrast to indirubin,some of the described azaindirubins emerged as potent inhibitors of CDK2/cylinA and compound 2b had more potent activity.Biological tests also showed that nitrogen atom at 7-position of azaindir...

  13. Comparative Study on the Antioxidant and Anti-Toxoplasma Activities of Vanillin and Its Resorcinarene Derivative

    Claudio B. S. Oliveira; Ywlliane S. R. Meurer; Marianne G. Oliveira; Wendy M. T. Q. Medeiros; Francisco O. N. Silva; Ana C. F. Brito; Daniel de L. Pontes; Andrade-Neto, Valter F

    2014-01-01

    A resorcinarene derivative of vanillin, resvan, was synthesized and characterized by spectroscopic techniques. We measured the cytotoxicity (in vivo and in vitro), antioxidant and anti-Toxoplasma activities of vanillin and the resorcinarene compound. Here we show that vanillin has a dose-dependent behavior with IC50 of 645 µg/mL through an in vitro cytotoxicity assay. However, we could not observe any cytotoxic response at higher concentrations of resvan (IC50 > 2,000 µg/mL). The in vivo a...

  14. Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil

    Jing Xiong

    2009-08-01

    Full Text Available A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (EDC•HCl and N-hydroxybenzotriazole (HOBt as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H-ylacetamido-3-(4-hydroxyphenyl propanoate showed more inhibitory effect against BEL-7402 than 5-FU.

  15. Theoretical insights on the antioxidant activity of edaravone free radical scavengers derivatives

    Cerón-Carrasco, José P.; Roy, Hélène M.; Cerezo, Javier; Jacquemin, Denis; Laurent, Adèle D.

    2014-04-01

    The prediction of antioxidant properties is not straightforward due to the complexity of the in vivo systems. Here, we use theoretical descriptors, including the potential of ionization, the electrodonating power and the spin density distribution, to characterize the antioxidant capacity of edaravone (EDV) derivatives. Our computations reveal the relationship between these parameters and their potential bioactivity as free radical scavengers. We conclude that more efficient antioxidants could be synthesized by tuning the R1 and R2 positions of the EDV structure, rather than modifying the R3 group. Such modifications might improve the antioxidant activity in neutral and deprotonated forms.

  16. Acetylcholinesterase-Inhibiting Activity of Pyrrole Derivatives from a Novel Marine Gliding Bacterium, Rapidithrix thailandica

    Khanit Suwanborirux; Anuchit Plubrukarn; Kornkanok Ingkaninan; Akkharawit Kanjana-opas; Supreeya Yuenyongsawad; Oraphan Sakulkeo; Yutthapong Sangnoi

    2008-01-01

    Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC50 4.9 mM). Two related pyrrole derivatives, 3-(2'-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 froma natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifac...

  17. Acetylcholinesterase-Inhibiting Activity of Pyrrole Derivatives from a Novel Marine Gliding Bacterium, Rapidithrix thailandica

    Sangnoi, Yutthapong; Sakulkeo, Oraphan; Yuenyongsawad, Supreeya; Kanjana-opas, Akkharawit; Ingkaninan, Kornkanok; Plubrukarn, Anuchit; Suwanborirux, Khanit

    2008-01-01

    Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC50 4.9 μM). Two related pyrrole derivatives, 3-(2′-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 from a natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifa...

  18. Proportional Derivative Active Force Control for “X” Configuration Quadcopter

    Niam Tamami

    2014-12-01

    Full Text Available This paper present a control method “x” configuration quadcopter. The control method used PDAFC (Proportional Derivative Active Force Control. PD is used to stabilize quadcopter, and AFC is used to reject uncertainty disturbance (e.g. wind by estimate disturbance torque value of quadcopter. By adding PD with AFC, better result is obtained, AFC can minimize uncertainty disturbance effect. The sensitivity toward uncertainty disturbance can be set from sensitivity constant to get best performance of disturbance rejection. Stability analysis of PDAFC was evaluated by Lyapunov stability theory.

  19. Characterization of Antiviral Activity of Benzamide Derivative AH0109 against HIV-1 Infection

    Chen, Liyu; Ao, Zhujun; Jayappa, Kallesh Danappa; Kobinger, Gary; Liu, ShuiPing; Wu, Guojun; Wainberg, Mark A.; Yao, Xiaojian

    2013-01-01

    In the absence of an effective vaccine against HIV-1 infection, anti-HIV-1 strategies play a major role in disease control. However, the rapid emergence of drug resistance against all currently used anti-HIV-1 molecules necessitates the development of new antiviral molecules and/or strategies against HIV-1 infection. In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 μM in HIV-1-susceptible CD...

  20. Anti-leukemia activity of semi-synthetic phenolic derivatives from Polygonum limbatum Meisn.

    Nkuété, Antoine Honoré Lonfouo; Kuete, Victor; Gozzini, Davide; Migliolo, Ludovico; Oliveira, Aline Lima; Wabo, Hippolyte K.; Tane, Pierre; Vidari, Giovanni; Efferth, Thomas; Franco, Octávio Luiz

    2015-01-01

    Background The present report describes the semi-synthesis of a few O-prenylated phenolic derivatives and their in vitro antitumor activities. These compounds were prepared by modifying two naturally occurring antitumor phenols, 5,7-dihydroxy-3-(1′-hydroxy-1′-phenyl-methyl)-6-methoxy-chroman-4-one (A) and 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (B), previously isolated from Polygonum limbatum Meisn. (Polygonaceae). The structures were elucidated by spectroscopic means and comparison with publ...

  1. Synthesis and In-vitro Antibacterial Activities of Acetylanthracene and Acetylphenanthrene Derivatives of Some Fluoroquinolones

    Shamsa, Fazel; Foroumadi, Alireza; Shamsa, Hashim; Samadi, Nasrin; Faramarzi, Mohammad Ali; Shafiee, Abbas

    2011-01-01

    Novel analogues of N-piperazinyl fluoroquinolones were prepared and evaluated against a panel of Gram-positive and Gram-negative bacteria, to study the effect of introducing bulky anthracene and phenanthrene moieties on the antibacterial effects of norfloxacin, ciprofloxacin and gatifloxacin. Although most of the novel synthesized compounds had lower antibacterial effects, some derivatives showed better activity in comparison with mother drugs based on molar concentration; for example, the 3-acetyl phenanthrene analogue of norfloxacin was more effective than E. coli and K. pneumonia. PMID:24250347

  2. Structural analysis and antitumor activity of androstane D-seco-mesyloxy derivatives

    Okljesa, Aleksandar M.; Jovanovic-Santa, Suzana S.; Sakac, Marija N.; Djurendic, Evgenija A.; Gasi, Katarina M. Penov, E-mail: suzana.jovanovic-santa@dh.uns.ac [University of Novi Sad (Serbia). Faculty of Sciences. Department of Chemistry, Biochemistry and Environmental Protection; Klisuric, Oliveira R. [University of Novi Sad (Serbia). Faculty of Sciences. Department of Physics; Jakimov, Dimitar S.; Aleksic, Lidija D. [Oncology Institute of Vojvodina, Sremska Kamenica (Serbia)

    2013-10-15

    he study of the influence of steroidal compounds on tumor cell cultures, cell growth, induction of apoptosis and/or cell cycle changes, is a common way of discovering potential therapeutics for treating people suffering from hormone-dependent problems and diseases. Because of the very high mortality rate associated with this class of disease, therapeutics for treating different types of cancers are among the most important. This work presents the synthesis of two stereoisomeric 16,17-secoandrostane mesyloxy derivatives and their 17-hydroxy precursors. Compounds were structurally analyzed by X-ray crystallography, and their antiproliferative activity, influence on the cell cycle and potential to induce apoptosis were investigated. (author)

  3. Antimycobacterial activity of a new rifamycin derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (T9).

    Reddy, V.M.; Nadadhur, G; Daneluzzi, D; Dimova, V; Gangadharam, P R

    1995-01-01

    The antimycobacterial activities of a new rifampin (RIF) derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (To), against 20 susceptible and multidrug-resistant strains of Mycobacterium tuberculosis and 20 Mycobacterium avium complex (MAC) strains were investigated. The radiometric MICs of T9 for M. tuberculosis were significantly lower than those of RIF. The MICs of T9 and RIF at which 90% of the RIF-susceptible strains were inhibited were < or = 0.25 and < or = 0.5 micrograms/ml...

  4. Lysine and pipecolic acid and some of their derivatives show anticonvulsant activity, and stimulation of benzodiazepine receptor activity

    Benzodiazepines are one of the most widely prescribed drugs in the treatment of anxiety, epilepsy and muscle tension. The natural products lysine and pipecolic acid known to be present in the animal, plant and microorganism, have been shown to be anticonvulsant against pentetrazol (PTZ)-induced seizures in mice. Methyl and ethyl esters of L-lysine and the N-isopropanol derivative of pipecolic acid appear to increase the anticonvulsant potency of the parent compounds, presumably due to their increase in hydrophobicity. Lysine and pipecolic acid showed significant stimulation of specific [3H]flunitrazepam (FZ) binding to mouse brain membranes. This stimulation was enhanced by chloride ions and stereospecific with L-isomer having higher effect. The dose-dependent anticonvulsant activity of lysine and pipecolic acid, and their stimulation of [3H]FZ binding appear to be correlated. The antiepileptic activity lysine, pipecolic acid and their derivatives therefore may be mediated through the γ-aminobutyric acid-benzodiazepine receptor complex

  5. Human-derived probiotic Lactobacillus reuteri demonstrate antimicrobial activities targeting diverse enteric bacterial pathogens.

    Spinler, Jennifer K; Taweechotipatr, Malai; Rognerud, Cheryl L; Ou, Ching N; Tumwasorn, Somying; Versalovic, James

    2008-06-01

    Lactobacillus reuteri is a commensal-derived anaerobic probiotic that resides in the human gastrointestinal tract. L. reuteri converts glycerol into a potent broad-spectrum antimicrobial compound, reuterin, which inhibits the growth of gram-positive and gram-negative bacteria. In this study, we compared four human-derived L. reuteri isolates (ATCC 55730, ATCC PTA 6475, ATCC PTA 4659 and ATCC PTA 5289) in their ability to produce reuterin and to inhibit the growth of different enteric pathogens in vitro. Reuterin was produced by each of the four L. reuteri strains and assessed for biological activity. The minimum inhibitory concentration (MIC) of reuterin derived from each strain was determined for the following enteric pathogens: enterohemorrhagic Escherichia coli, enterotoxigenic E. coli, Salmonella enterica, Shigella sonnei and Vibrio cholerae. We also analyzed the relative abilities of L. reuteri to inhibit enteric pathogens in a pathogen overlay assay. The magnitude of reuterin production did not directly correlate with the relative ability of L. reuteri to suppress the proliferation of enteric pathogens. Additional antimicrobial factors may be produced by L. reuteri, and multiple factors may act synergistically with reuterin to inhibit enteric pathogens. PMID:18396068

  6. Bivalent transition metal complexes of coumarin-3-yl thiosemicarbazone derivatives: Spectroscopic, antibacterial activity and thermogravimetric studies

    Refat, Moamen S.; El-Deen, Ibrahim M.; Anwer, Zeinab M.; El-Ghol, Samir

    2009-02-01

    Schiff base complexes of Cu(II), Co(II) and Ni(II) with two coumarin-3-yl thiosemicarbazone derivatives (1E)-1-(1-(2-oxo-2H-chromen-3-yl)ethylidene)thiosemicarbazide (OCET) and (1E)-1-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)thiosemicarbazide (BOCET) were synthesized by the reaction of Cu(II), Co(II) and Ni(II) chlorides with each mentioned ligand with molar ratio 1:2 metal-to-ligand. Both ligands and their metal complexes were characterized by different physicochemical methods, elemental analysis, molar conductivity, (UV-vis, Mass, Infrared, 1H NMR spectra) and also thermal analysis (TG and DTG) techniques. The discussion of the outcome data of the prepared complexes indicate that the coumarin-3-yl thiosemicarbazone derivatives ligands behave as a bidentate ligand through both thione sulphur and azomethine nitrogen with 1:2 (metal:ligand) stoichiometry for all complexes. The molar conductance measurements proved that the complexes are electrolytes. The kinetic thermodynamic parameters such as: E∗, Δ H∗, Δ S∗and Δ G∗are calculated from the DTG curves, all complexes are more ordered except Ni(II) complexes. The antibacterial activity of the coumarin-3-yl thiosemicarbazone derivatives and their metal complexes was evaluated against some kinds of Gram positive and Gram negative bacteria.

  7. Bioconversion of volatile fatty acids derived from waste activated sludge into lipids by Cryptococcus curvatus.

    Liu, Jia; Liu, Jia-Nan; Yuan, Ming; Shen, Zi-Heng; Peng, Kai-Ming; Lu, Li-Jun; Huang, Xiang-Feng

    2016-07-01

    Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fatty acids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. PMID:27038264

  8. Preparation, antioxidant and antitumor activities in vitro of different derivatives of levan from endophytic bacterium Paenibacillus polymyxa EJS-3.

    Liu, Jun; Luo, Jianguang; Ye, Hong; Zeng, Xiaoxiong

    2012-03-01

    A levan-type exopolysaccharide (EPS) from Paenibacillus polymyxa EJS-3 was successfully acetylated, phosphorylated and benzylated, respectively, affording its derivatives of acetylated levan (AL), phosphorylated levan (PL) and benzylated levan (BL). Then, the antioxidant and antitumor activities in vitro of the natural polysaccharide and its derivatives were determined. As results, AL, BL and PL all exhibited higher reducing power, scavenging activity against superoxide radical and scavenging activity on hydroxyl radical than the natural polysaccharide, EPS-1. In addition, AL, BL and PL also exhibited higher antiproliferative activity against human gastric cancer BGC-823 cells in vitro than EPS-1. The enhanced activities of the derivatives were probably due to the introduction of acetyl, benzyl, or phosphoryl groups into EPS-1 molecules that increased electron-donating ability and affinity with the receptors on immune cells. The results suggested that the derivatives could be explored as promising antioxidant and antitumor agents. PMID:22142695

  9. Antiviral and Quantitative Structure Activity Relationship Study for Dihydropyridones Derived from Curcumin

    Bahjat A. Saeed

    2010-01-01

    Full Text Available Problem statement: Pyridones are known to have variety of biological activities like antitumor, antibacterial, anti-inflammatory and antimalarial activities. This study presents antiviral evaluation of dihydropyridones derived from curcumin, as well as curcumin for comparison. Approach: The compounds evaluated for their in vitro antiviral activities against the viruses: HIV-1, Bovin viral Diarrhea, Yellow Fever, Reovirus 1, Herpesvirus 1, Vaccinia, Vescular Stomatitis, Coxackie virus B2, Poliovirus 1 and Respiratory Syncytial viruses by using Microculture Tetrazolium assay (MTT method. The method was based on the metabolic reduction of 3-(4,5-dimethylthiazol-2- yl-2,5-diphenyltetrazolium bromide. Results: Antiviral biological activities represented as CC50 were within the range >100-26 for BHK-21, while they were within the range >90-≥13 against Respiratory Syncytial Virus when represented as EC50 for example. Both CC50 and EC50 values were found to increase with increasing chain length of the substituent on the nitrogen atom. Conclusion: The in vitro antiviral activities of the tested dihydropyridones can be enhanced by increasing chain length of the substituent on the nitrogen atom.

  10. Effect of root derived organic acids on the activation of nutrients in the rhizosphere soil

    2002-01-01

    Four types of soils, including brown coniferous forest soil, dark brown soil, black soil, and black calic soil, sampled from three different places in northeast China were used in this test. The functions of two root-derived organic acids and water were simulated and compared in the activation of mineral nutrients from the rhizosphere soil. The results showed that the organic acids could activate the nutrients and the activated degree of the nutrient elements highly depended on the amount and types of the organic acid excreted and on the physiochemical and biochemical properties of the soil tested. The activation effect of the citric acid was obviously higher than that of malic acid in extracting Fe, Mn, Cu, and Zn for all the tested soil types. However, the activation efficiencies of P, K, Ca, and Mg extracting by the citric acid were not much higher, sometimes even lower, than those by malic acid. The solution concentration of all elements increased with increase of amount of the citric acid added.

  11. Composite electrodes of activated carbon derived from cassava peel and carbon nanotubes for supercapacitor applications

    Taer, E.; Iwantono, Yulita, M.; Taslim, R.; Subagio, A.; Salomo, Deraman, M.

    2013-09-01

    In this paper, a composite electrode was prepared from a mixture of activated carbon derived from precarbonization of cassava peel (CP) and carbon nanotubes (CNTs). The activated carbon was produced by pyrolysis process using ZnCl2 as an activation agent. A N2 adsorption-desorption analysis for the sample indicated that the BET surface area of the activated carbon was 1336 m2 g-1. Difference percentage of CNTs of 0, 5, 10, 15 and 20% with 5% of PVDF binder were added into CP based activated carbon in order to fabricate the composite electrodes. The morphology and structure of the composite electrodes were investigated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. The SEM image observed that the distribution of CNTs was homogeneous between carbon particles and the XRD pattern shown the amorphous structure of the sample. The electrodes were fabricated for supercapacitor cells with 316L stainless steel as current collector and 1 M sulfuric acid as electrolyte. An electrochemical characterization was performed by using an electrochemical impedance spectroscopy (EIS) method using a Solatron 1286 instrument and the addition of CNTs revealed to improve the resistant and capacitive properties of supercapacitor cell.

  12. The effects of electrolyte on the supercapacitive performance of activated calcium carbide-derived carbon

    Wu, Hao; Wang, Xianyou; Jiang, Lanlan; Wu, Chun; Zhao, Qinglan; Liu, Xue; Hu, Ben'an; Yi, Lanhua

    2013-03-01

    Porous calcium carbide-derived carbon (CCDC) has been prepared by one-step route from CaC2 in a freshly prepared chlorine environment at lower temperature, and following activated by ZnCl2 to get activated CCDC. The performances of the supercapacitors based on activated CCDC as electrode active material in aqueous KOH, K2SO4, KCl and KNO3 electrolytes are studied by cyclic voltammetry, constant current charged/discharged, cyclic life and electrochemical impedance spectroscopy. It has been found that the supercapacitor using 6 M KOH as electrolyte shows an energy density of 8.3 Wh kg-1 and a power density of 1992 W kg-1 based on the total weight of the electrode active materials with a voltage range 0 V-1 V. Meanwhile, the specific capacitance of the supercapacitor in 6 M KOH electrolyte is 68 F g-1 at the scan rate of 1 mV s-1 in the voltage range of 0 V-1 V, the charge-transfer resistance is extremely low and the relaxation time is the least of all. The supercapacitor also exhibits a good cycling performance and keeps 95% of initial capacity over 5000 cycles.

  13. The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

    McAllister, Sean D; Soroceanu, Liliana; Desprez, Pierre-Yves

    2015-06-01

    As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ(9)-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment. PMID:25916739

  14. Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of inflammatory activators and hypoxia.

    Maceckova, Michaela; Martiskova, Hana; Koudelka, Adolf; Kubala, Lukas; Lojek, Antonin; Pekarova, Michaela

    2015-11-01

    Caveolins are specific proteins involved in regulation of signal transduction to intracellular space. Still, their contribution to immune functions has not been completely clarified. Thus, we decided to characterize the expression of caveolins in bone marrow-derived macrophages (BMDMs) under resting and inflammatory conditions. The effect of classical activators (lipopolysaccharide, LPS; interferon-gamma, IFN-γ) was further potentiated with hypoxic (5% O2) conditions. The activation of p44/42-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and expression of caveolin-1, -2, and -3, hypoxia inducible factor-1 alpha (HIF-1α), as well as inducible nitric oxide synthase (iNOS) was monitored using the Western blot technique. The production of nitric oxide (NO) and tumor necrosis factor-alpha (TNFα) was analyzed by Griess method or ELISA, respectively. BMDMs were also transfected with siRNA against caveolin-2. Importantly, our study showed for the first time that BMDMs expressed only caveolin-2, and its level decreased after activation of macrophages with LPS, IFN-γ, and/or hypoxia. The expression of caveolin-2 negatively correlates with the iNOS and HIF-1α protein levels, as well as with the LPS/IFN-γ- and hypoxia-induced activation of ERK1/2. We concluded that caveolin-2 is most probably involved in regulation of pro-inflammatory responses of BMDMs, triggered via activation of ERK1/2. PMID:26215374

  15. Occurrence of fipronil and its biologically active derivatives in urban residential runoff.

    Gan, J; Bondarenko, S; Oki, L; Haver, D; Li, J X

    2012-02-01

    Insecticides are commonly used around homes for controlling insects such as ants, termites, and spiders. Such uses have been linked to pesticide contamination and toxicity in urban aquatic ecosystems. Fipronil is a relatively new and popular urban-use insecticide that has acute toxicity to arthropods at low-ppb levels. In this study, we collected runoff water from 6 large communities, each consisting of 152 to 460 single-family homes, in Sacramento County and Orange County, California, and evaluated the occurrence of fipronil and its biologically active derivatives over 26 months under dry weather conditions. Statistical modeling showed that the levels of fipronil and derivatives in the runoff water were both spatially and temporally correlated. More than 10-fold differences were observed between the Sacramento and Orange County sites, with the much higher levels for Orange County (southern California) coinciding with heavier use. The median concentrations of combined fipronil and derivatives for the Orange County sites were 204-440 ng L(-1), with the 90th percentile levels ranging from 340 to 1170 ng L(-1). These levels frequently exceeded the LC50 values for arthropods such as mysid shrimp and grass shrimp. The highest levels occurred from April to October, while decreases were seen from October to December and from January to March, likely reflecting seasonal use patterns and the effect of rain-induced washoff. Fipronil and fipronil sulfone (oxidation derivative) each accounted for about 35% of the total concentrations, with desulfinyl fipronil (a photolytic product) contributing about 25%. Results of this study clearly established residential drainage as a direct source for pesticide contamination in urban waterways, and for the first time, identified fipronil as a new and widespread contaminant with potential ecotoxicological significance. PMID:22242791

  16. Design, Synthesis, and Potential Antidepressant-like Activity of 7-prenyloxy-2,3-dihydroflavanone Derivatives.

    Zhen, Xing-Hua; Quan, Ying-Chun; Peng, Zhou; Han, Yan; Zheng, Zhou-Jun; Guan, Li-Ping

    2016-06-01

    A series of 7-prenyloxy-2, 3-dihydroflavanone derivatives were synthesized and screened for their antidepressant-like activity. Among them, it was observed that compounds 5j and 5k were found to be the most antidepressant-like activity. In addition, it was found that compounds 5j and 5k significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus, and cortex. Compounds 5j and 5k also significantly increased the contents of 5-HIAA in the hippocampus and cortex, shut down 5-HT metabolism compared with mice treated with stress vehicle. These results suggested that compounds 5j and 5k displayed potent antidepressant-like properties that were mediated via neurochemical systems. PMID:26705885

  17. Synthesis and Anti-Intestinal Nematode Activity of Variously Substituted Benzonaphthyridine Derivatives

    Ai-Dan Wen

    2011-02-01

    Full Text Available A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1H-NMR, 13C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4′-(1H-indol-5′-ylmethyleneaminophenyl-amino-benzo[b][1,5] naphthyridine (4n produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs.

  18. Antibacterial activity of commercially available plant-derived essential oils against oral pathogenic bacteria.

    Bardají, D K R; Reis, E B; Medeiros, T C T; Lucarini, R; Crotti, A E M; Martins, C H G

    2016-05-01

    This work investigated the antibacterial activity of 15 commercially available plant-derived essential oils (EOs) against a panel of oral pathogens. The broth microdilution method afforded the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the assayed EOs. The EO obtained from Cinnamomum zeylanicum (Lauraceae) (CZ-EO) displayed moderate activity against Fusobacterium nucleatum (MIC and MBC = 125 μg/mL), Actinomyces naeslundii (MIC and MBC = 125 μg/mL), Prevotella nigrescens (MIC and MBC = 125 μg/mL) and Streptococcus mutans (MIC = 200 μg/mL; MBC = 400 μg/mL). (Z)-isosafrole (85.3%) was the main chemical component of this oil. We did not detect cinnamaldehyde, previously described as the major constituent of CZ-EO, in specimens collected in other countries. PMID:26165725

  19. Application of activated carbon derived from scrap tires for adsorption of Rhodamine B.

    Li, Li; Liu, Shuangxi; Zhu, Tan

    2010-01-01

    Activated carbon derived from solid hazardous waste scrap tires was evaluated as a potential adsorbent for cationic dye removal. The adsorption process with respect to operating parameters was investigated to evaluate the adsorption characteristics of the activated pyrolytic tire char (APTC) for Rhodamine B (RhB). Systematic research including equilibrium, kinetics and thermodynamic studies was performed. The results showed that APTC was a potential adsorbent for RhB with a higher adsorption capacity than most adsorbents. Solution pH and temperature exert significant influence while ionic strength showed little effect on the adsorption process. The adsorption equilibrium data obey Langmuir isotherm and the kinetic data were well described by the pseudo second-order kinetic model. The adsorption process followed intra-particle diffusion model with more than one process affecting the adsorption process. Thermodynamic study confirmed that the adsorption was a physisorption process with spontaneous, endothermic and random characteristics. PMID:21179969

  20. Nonactivated and Activated Biochar Derived from Bananas as Alternative Cathode Catalyst in Microbial Fuel Cells

    Haoran Yuan

    2014-01-01

    Full Text Available Nonactivated and activated biochars have been successfully prepared by bananas at different thermotreatment temperatures. The activated biochar generated at 900°C (Biochar-act900 exhibited improved oxygen reduction reaction (ORR and oxygen evolution reaction (OER performances in alkaline media, in terms of the onset potential and generated current density. Rotating disk electron result shows that the average of 2.65 electrons per oxygen molecule was transferred during ORR of Biochar-act900. The highest power density of 528.2 mW/m2 and the maximum stable voltage of 0.47 V were obtained by employing Biochar-act900 as cathode catalyst, which is comparable to the Pt/C cathode. Owning to these advantages, it is expected that the banana-derived biochar cathode can find application in microbial fuel cell systems.

  1. Naturally occurring amino acid derivatives with herbicidal, fungicidal or insecticidal activity.

    Lamberth, Clemens

    2016-04-01

    Several naturally occurring amino acid derivatives display significant activities against weeds, fungi and insects: some of them have been even commercialized and are applied as crop protection agents. The 53 most important amino acid natural products with such efficacy are presented in this review together with their natural source, mode of action and biological activity. The diversity of the manifold bacterial, fungal and plantal sources of these compounds is impressive as well as their completely different structural scaffolds, ranging from cyclopeptides via unique non-proteinogenic amino acids to peptidyl nucleosides, the broad range of target enzymes from several different biochemical pathways, which they inhibit and also the plethora of different weeds, fungi and insects they are able to control. PMID:26801938

  2. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    Huang, T; Larsen, K T; Ried-Larsen, M;

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies....... met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational...

  3. Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives.

    França, Paulo H B; Da Silva-Júnior, Edeildo F; Aquino, Pedro G V; Santana, Antônio E G; Ferro, Jamylle N S; De Oliveira Barreto, Emiliano; Do Ó Pessoa, Cláudia; Meira, Assuero Silva; De Aquino, Thiago M; Alexandre-Moreira, Magna S; Schmitt, Martine; De Araújo-Júnior, João X

    2016-03-01

    Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L-1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents. PMID:26959549

  4. Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

    França Paulo H. B.

    2016-03-01

    Full Text Available Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma, MDA-MB-435 (melanoma and SF-295 (glioblastoma were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

  5. Synthesis, x-ray crystallography and leishmanicidal activity of benzimidazolinyl piperidine derivative

    Protozoan parasites of the Leishmania genus are the main cause of vector-borne disease leishmaniasis throughout the world. It is caused by at least 17 different species of protozoan Leishmania and transmitted by the bite of infected sand flies. Leishmaniasis could be fatal. Present drugs have limitations to cure it due to the development of drug resistance. Hence, to design an effective leishmanicidal agent would be of great interest. Benzimidazolinyl piperidine has served as potential target due to a vast range of biological activities. In the present study a new 4-(2-keto-1-benzimidazolinyl)piperidine derivative, 1-(2-(4-fluorophenyl)-2-oxoethyl)-4-(2-oxo-2,3-dihydro-1H-benzo(d)imidazol) piperidinium bromide has been synthesized and characterized by X-ray crystallography, 1D and 2D NMR spectroscopy. Evaluation by in vitro leishmanicidal assay showed good activity. (author)

  6. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Breuer, Aviva; Haj, Christeene G; Fogaça, Manoela V; Gomes, Felipe V; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A; Hallak, Jaime C; Crippa, José A; Zuardi, Antonio W; Mechoulam, Raphael; Guimarães, Francisco S

    2016-01-01

    Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. PMID:27416026

  7. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Aviva Breuer

    Full Text Available Cannabidiol (CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101 (1, is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  8. Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor.

    Ma, Ming-Liang; Li, Ming; Gou, Jiao-Jiao; Ruan, Tian-Yu; Jin, Hai-Shan; Zhang, Ling-Hong; Wu, Liang-Chun; Li, Xiao-Yan; Hu, Ying-He; Wen, Ke; Zhao, Zheng

    2014-11-01

    Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure-activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2'-fluoride group in ring B were essential for this class of compounds to be active against NMU2R. PMID:25262941

  9. Antileishmanial activity of natural diterpenes from Cistus sp. and semisynthetic derivatives thereof.

    Fokialakis, Nikolas; Kalpoutzakis, Eleftherios; Tekwani, Babu Lal; Skaltsounis, Alexios Leandros; Duke, Stephen Oscar

    2006-08-01

    Eleven cis-clerodane diterpenes, seven labdane type diterpenes and one triterpene isolated from Cistus monspeliensis and the resin "Ladano" of Cistus creticus subsp. creticus were evaluated against Leishmania donovani promastigotes, the causative agent for visceral leishmaniasis. In addition, eleven semisynthetic manoyl oxide, seventeen labdane type derivatives and a triterpene were also evaluated for their antileishmanial activity. 18-Acetoxy-cis-clerod-3-en-15-ol, 15,18-diacetoxy-cis-clerod-3-ene and 13-(E)-8a-hydroxylabd-13-en-15-ol 2-chloroethylcarbamate exhibited the most potent and selective leishmanicidal activity with IC50 values of 3.3 microg/ml, 3.4 microg/ml and 3.5 microg/ml, respectively. PMID:16880643

  10. Design, synthesis and antiproliferative activity studies of novel dithiocarbamate-chalcone derivates.

    Fu, Dong-Jun; Zhang, Sai-Yang; Liu, Ying-Chao; Zhang, Li; Liu, Jun-Ju; Song, Jian; Zhao, Ruo-Han; Li, Feng; Sun, Hui-Hui; Liu, Hong-Min; Zhang, Yan-Bing

    2016-08-15

    A series of novel dithiocarbamate-chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC50 values of 2.03μM and 2.46μM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase. PMID:27423479

  11. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

    Fogaça, Manoela V.; Gomes, Felipe V.; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A.; Hallak, Jaime C.; Crippa, José A.; Zuardi, Antonio W.; Guimarães, Francisco S.

    2016-01-01

    Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors. PMID:27416026

  12. New Lipophilic Piceatannol Derivatives Exhibiting Antioxidant Activity Prepared by Aromatic Hydroxylation with 2-Iodoxybenzoic Acid (IBX

    Roberta Bernini

    2009-11-01

    Full Text Available Piceatannol (E-3,5,3’,4’-tetrahydroxystilbene is a phytoalexin synthesized in grapes in response to stress conditions. It exhibits strong antioxidant and antileukaemic activities due to the presence of the catechol moiety. To modify some physical properties like solubility, and miscibility in non-aqueous media some new previously unreported piceatannol derivatives having lipophilic chains on the A-ring were prepared in good yields by a simple and efficient procedure. The key step was a chemo- and regioselective aromatic hydroxylation with 2-iodoxybenzoic acid (IBX. The new compounds showed antioxidant activity and seemed promising for possible applications as multifunctional emulsifiers in food, cosmetic and pharmaceutical fields.

  13. Synthesis and Antiviral Activity of N-Phenylbenzamide Derivatives, a Novel Class of Enterovirus 71 Inhibitors

    Zhuo-Rong Li

    2013-03-01

    Full Text Available A series of novel N-phenylbenzamide derivatives were synthesized and their anti-EV 71 activities were assayed in vitro. Among the compounds tested, 3-amino-N-(4-bromophenyl-4-methoxybenzamide (1e was active against the EV 71 strains tested at low micromolar concentrations, with IC50 values ranging from 5.7 ± 0.8–12 ± 1.2 μM, and its cytotoxicity to Vero cells (TC50 = 620 ± 0.0 μM was far lower than that of pirodavir (TC50 = 31 ± 2.2 μM. Based on these results, compound 1e is a promising lead compound for the development of anti-EV 71 drugs.

  14. Synthesis and Antifungal Activity of Novel Sulfone Derivatives Containing 1,3,4-Oxadiazole Moieties

    Maoguo Tong

    2011-11-01

    Full Text Available A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC50 values of 5.21 μg/mL, 8.25 µg/mL, 8.03 µg/mL, and 21.00 µg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.

  15. Catecholase activity investigations using in situ copper complexes continuing Schiff base derivatives with a theoretical calculation

    A. Djedouani

    2015-03-01

    Full Text Available The study of catecholase activity of a series of Schiff base compounds using in situ copper complexes of 4-hydroxy-6-methyl-3-(1-(phenyliminoethyl-2H-pyran-2-one derivatives has been reported. The reaction rate depends on four parameters: The nature of the substitution in para position to the benzene ring, the nature of counter anion, the concentration of ligand and the nature of solvent. The highest rate activity is given by complex resulting from one equivalent of ligand L2 and two equivalents of copper acetate in methanol, which equal to 62.25 µmol.min-1.L-1.In other part, a theoretical study of such ligands using the semi-empirical method AM1 were also investigated. A good relationship founded between the maximal reaction rate (Vmax and the HOMO energy (Pearson correlation: r=-0.794.

  16. Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil

    Khoshayand Mohammad

    2012-07-01

    Full Text Available Abstract Background and the purpose of the study Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In the present investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions was investigated. Methods 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substituted benzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29 cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively. Results and major conclusion Findings of the present study

  17. Cytotoxicity and Radiosensitising Activity of Synthesized Dinitrophenyl Derivatives of 5-Fluorouracil

    Khosrou Abdi

    2012-07-01

    Full Text Available Background and the purpose of the study: Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In thepresent investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide,and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions wasinvestigated.Methods: 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substitutedbenzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking,group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively.Results and major conclusion: Findings of the present study showed that

  18. Antipathogenic effects of structurally-related Schiff base derivatives: Structure–activity relationship

    Soleiman Hisaindee

    2015-11-01

    Full Text Available Eighteen structurally-related Schiff base derivatives, which belong to salicylidenebenzylamine and 2-hydroxy-1-naphthylidenebenzylamine families were prepared and characterized by spectroscopic techniques. All the synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Human pathogenic gram-negative (Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens, gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtilis, and fungi (Alternaria alternata, Aspergillus niger, Penicillium roqueforti, and Saccharomyces cerevisiae were evaluated based on their toxicity to different concentrations of Schiff base compounds. For assessment of toxicity to pathogens, a disc diffusion assay was used to test the antimicrobial properties. The results revealed some antimicrobial activities of some of the synthesized compounds. Among the tested pathogens, the synthesized salicylidinaniline derivatives show highly potent action towards Alternaria alternata. Interestingly, a compound which contains the –Cl group is only effective against gram negative bacteria, but not gram positive bacteria. No remarkable antibacterial or antifungal activities were observed in the presence of –CH3 or –Br group. Furthermore, most of the naphthalene-containing compounds show no growth retardation towards bacterial or fungal pathogens. On the other hand, the presence of –OH or –SH group at para or ortho position, respectively, on the aniline site is correlated with an increased inhibitory drug effect on all pathogens. The importance of our findings to the drug research and developments is discussed in the context of finding a correlation between the structural properties of the new drugs and their biological activities.

  19. IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

    Kuppusamy Asokkumar

    2012-09-01

    Full Text Available Objective Soluble epoxide hydrolase (sEH belongs to the α/β -hydrolase superfamily, a subclass of α/β proteins. Chalcones are chemical compounds that show hopeful obliging efficacy in controlling numerous diseases. The main objective of the study is to evaluate the sEH inhibitory activity of some synthesized chalcone derivatives and identification of its mode of inhibition. Methods Four different chalcone derivatives (PC-1 to PC-4 were selected for synthesis by Claisen-Schmidt method. The in vitro sEH inhibitory activity was performed for the synthesized compounds by fluorimetric assay. The percentage of sEH activity and IC50 values were calculated for the synthesized compounds. Dissociation constant were determined by following the method described by Lineweaver-Burks plot.Results and Conclusions The IC50 value obtained for PC-1, PC-2, PC-3, and PC-4 were found to be 0.8213 µg/mL, 2.64 µg/mL, 0.2490 µg/mL and 0.5238 µg/mL respectively. The order of potency (IC50 of the chalcone and chalcone oxide in sEH inhibition assay was PC-3 > PC-4 > PC-1 >PC-2. All the compounds (PC-1, PC-2, PC-3 showed mixed type of inhibition except PC-4 which showed non-competitive type of inhibition. Further in vivo studies are to be carried out for these compounds to confirm their activity and explore the mechanism by which these compounds act and rationalize their use.

  20. Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

    Bekdemir Yunus

    2008-08-01

    Full Text Available Abstract Background Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance. Methods Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested. Results The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably. Conclusion This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.

  1. Effects of amino acid derivatives on physical, mental, and physiological activities.

    Luckose, Feby; Pandey, Mohan Chandra; Radhakrishna, Kolpe

    2015-01-01

    Nutritional ergogenic aids have been in use for a long time to enhance exercise and sports performance. Dietary components that exhibit ergogenic activity are numerous and their consumption is common and popular among athletes. They often come under scrutiny by legal authorities for their claimed benefits and safety concerns. Amino acid derivatives are propagated as being effective aids to enhance physical and mental performance in many ways, even though studies have pointed out that individuals who are deficient are more likely to benefit from dietary supplementation of amino acid derivatives than normal humans. In this review, some of the most common and widely used amino acids derivatives in sports and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been discussed for their effects on exercise performance, mental activity as well as body strength and composition. Creatine, carnitine, HMB, and taurine are reported to delay the onset of fatigue, improve exercise performance, and body strength. HMB helps in increasing fat-free mass and reduce exercise induced muscle injury. Taurine has been found to reduce oxidative stress during exercise and also act as an antihypertensive agent. Although, studies have not been able to find any favorable effect of tyrosine administration on exercise performance, it has been proved to be very effective in fighting stress, improving mood and cognitive performance particularly in sleep-deprived subjects. While available data from published studies and findings are equivocal about the efficacy of creatine, tyrosine, and HMB, more comprehensive researches on carnitine and taurine are necessary to provide evidence for the theoretical basis of their ergogenic role in nutritional modification and supplementation. PMID:24279396

  2. Structural characteristics and antiviral activity of multiple peptides derived from MDV glycoproteins B and H

    Wang Ming

    2011-04-01

    Full Text Available Abstract Background Marek's disease virus (MDV, which is widely considered to be a natural model of virus-induced lymphoma, has the potential to cause tremendous losses in the poultry industry. To investigate the structural basis of MDV membrane fusion and to identify new viral targets for inhibition, we examined the domains of the MDV glycoproteins gH and gB. Results Four peptides derived from the MDV glycoprotein gH (gHH1, gHH2, gHH3, and gHH5 and one peptide derived from gB (gBH1 could efficiently inhibit plaque formation in primary chicken embryo fibroblast cells (CEFs with 50% inhibitory concentrations (IC50 of below 12 μM. These peptides were also significantly able to reduce lesion formation on chorioallantoic membranes (CAMs of infected chicken embryos at a concentration of 0.5 mM in 60 μl of solution. The HR2 peptide from Newcastle disease virus (NDVHR2 exerted effects on MDV specifically at the stage of virus entry (i.e., in a cell pre-treatment assay and an embryo co-treatment assay, suggesting cross-inhibitory effects of NDV HR2 on MDV infection. None of the peptides exhibited cytotoxic effects at the concentrations tested. Structural characteristics of the five peptides were examined further. Conclusions The five MDV-derived peptides demonstrated potent antiviral activity, not only in plaque formation assays in vitro, but also in lesion formation assays in vivo. The present study examining the antiviral activity of these MDV peptides, which are useful as small-molecule antiviral inhibitors, provides information about the MDV entry mechanism.

  3. Synthesis and trypanocidal activity of 7, 2'-dioxygenated isoflavones and oxypropanolamine derivatives

    Faria, Terezinha de J. [Universidade Estadual de Londrina, PR (Brazil). Dept. de Quimica]. E-mail: tjfaria@uel.br; Silva, Luiz G. Fonseca e; Souza Filho, Jose D. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Quimica; Chiari, Egler [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Parasitologia; Oliveira, Alaide B. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Dept. de Produtos Farmaceuticos

    2005-11-15

    '-Dihydroxyisoflavone was shown to be active against the bloodstream trypomastigote form of Trypanosoma cruzi, the etiologic agent of Chagas' disease. Amphiphilic derivatives of this isoflavone were synthesized aiming to obtain hydrosoluble compounds of potential use as prophylactic agents to be added to blood for transfusion. This isoflavone was obtained by demethylation of 7-hydroxy-2'-methoxyisoflavone that was synthesized via the intermediate deoxybenzoin. Its reaction with epichlorohydrin, followed by aminolysis with diethylamine, afforded the 7-oxypropanolamine which on treatment with methyl iodide gave the corresponding ammonium salt. The 7-hydroxy-2'-methoxyisoflavone was inactive in the in vitro assays, the 7-oxypropanolamine was more active than 7, 2'-dihydroxyisoflavone while the ammonium salt has not eliminated the parasite from the blood besides causing total lysis of the erythrocytes. The simple synthetic procedures described in the present paper can be used to provide gram quantities of 7, 2'-dihydroxyisoflavone and its 7-oxypropanolamine derivative that should be further investigated in in vivo murine models as potential chemotherapeutic agents for treatment of Chagas' disease. (author)

  4. Synthesis, crystal structure, superoxide scavenging activity, anticancer and docking studies of novel adamantyl nitroxide derivatives

    Zhu, Xiao-he; Sun, Jin; Wang, Shan; Bu, Wei; Yao, Min-na; Gao, Kai; Song, Ying; Zhao, Jin-yi; Lu, Cheng-tao; Zhang, En-hu; Yang, Zhi-fu; Wen, Ai-dong

    2016-03-01

    A novel adamantyl nitroxide derivatives has been synthesized and characterized by IR, ESI-MS and elemental analysis. Quantum chemical calculations have also been performed to calculate the molecular geometry using density functional theory (B3LYP) with the 6-31G (d,p) basis set. The calculated results showed that the optimized geometry can well reproduce the crystal structure. The antioxidant and antiproliferative activity were evaluated by superoxide (NBT) and MTT assay. The adamantyl nitroxide derivatives exhibited stronger scavenging ability towards O2· - radicals when compared to Vitamin C, and demonstrated a remarked anticancer activity against all the tested cell lines, especially Bel-7404 cells with IC50 of 43.3 μM, compared to the positive control Sorafenib (IC50 = 92.0 μM). The results of molecular docking within EGFR using AutoDock confirmed that the titled compound favorably fitted into the ATP binding site of EGFR and would be a potential anticancer agent.

  5. Trypanosoma cruzi: evaluation of (-)-cubebin derivatives activity in the messenger RNAs processing.

    Andrade e Silva, Márcio Luís; Cicarelli, Regina Maria Barretto; Pauletti, Patrícia M; Luz, Priscilla Paiva; Rezende, Karen Cristina Souza; Januário, Ana Helena; da Silva, Rosangela; Pereira, Ana Carolina; Bastos, Jairo Kenupp; de Albuquerque, Sérgio; Magalhães, Lizandra Guidi; Cunha, Wilson Roberto

    2011-08-01

    No fully effective treatment has been developed since the discovery of Chagas' disease. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effective in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing, which is unusual RNA processing reaction, and it implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. Cubebin derivatives seem to provide treatments with less collateral effects than benznidazole and showed similar or better trypanocidal activities than benznidazole. Therefore, the cubebin derivatives ((-)-6,6'-dinitrohinokinin (DNH) and (-)-hinokinin (HQ)) interference in the mRNA processing was evaluated using T. cruzi permeable cells (Y and BOL (Bolivia) strains) following by RNase protection reaction. These substances seem to intervene in any step of the RNA transcription, promoting alterations in the RNA synthesis, even though the RNA processing mechanism still occurs. Furthermore, HQ presented better activity against the parasites than DNH, meaning that BOL strain seems to be more resistant than Y. PMID:21327990

  6. The in Vitro Structure-Related Anti-Cancer Activity of Ginsenosides and Their Derivatives

    Liang Liu

    2011-12-01

    Full Text Available Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE, protopanaxadiol (PPD-type, protopanaxatriol (PPT-type ginsenosides fractions, and their hydrolysates, which were prepared by stepwise hydrolysis of the sugar moieties of the ginsenosides. The results showed that the cytotoxic potency of the hydrolysates of RSE and total PPD-type or PPT-type ginsenoside fractions was much stronger than the original RSE and ginsenosides; especially the hydrolysate of PPD-type ginsenoside fractions. Subsequently, two derivatives of protopanaxadiol (1, compounds 2 and 3, were synthesized via hydrogenation and dehydration reactions of compound 1. Using those two derivatives and the original ginsenosides, a comparative study on various cancer cell lines was conducted; the results demonstrated that the cytotoxic potency was generally in the descending order of compound 3 > 20(S-dihydroprotopanaxadiol (2 > PPD (1 > 20(S-Rh2 > 20(R-Rh2 ≈ 20(R-Rg3 ≈ 20(S-Rg3. The results clearly indicate the structure-related activities in which the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells.

  7. Molluscicidal activity of 2-hydroxy-[1,4]naphthoquinone and derivatives

    Celso A. Camara

    2008-06-01

    Full Text Available The toxic profile of lawsone (2-hydroxy-[1,4]naphthoquinone and a series of [1,4]naphthoquinone derivatives was evaluated against the brine shrimp Artemia salina and against the mollusk Biomphalaria glabrata, the main transmitting vector of schistosomiasis in Brazil. Of the seventeen compounds tested nine fell below the threshold of 100 µg/mL set for potential molluscicidal activity by the World Health Organization. As a general rule derivatives with non-polar substituents presented the highest molluscicidal activities. These substances showed significant toxicity in A. salina lethality bioassay.A toxicidade da lausona (2-hidroxi-1,4-naftoquinona e de diversos derivados foi avaliada frente à Artemia salina e ao molusco Biomphalaria glabrata, o principal vetor de transmissão da esquistossomose no Brasil. Entre os dezessete compostos testados, nove apresentaram um perfil de toxicidade menor que 100 µg/mL, sendo potenciais agentes moluscicidas de acordo com as designações da Organização Mundial da Saúde. No presente estudo, os compostos contendo substituintes apolares exibiram as maiores atividades. Estes compostos também se mostraram significantemente tóxicos frente à A. salina.

  8. Cationic chlorophyl derivatives with SOD mimicking activity suppress the proliferation of human ovarian cancer cells.

    Kobayashi, Y; Maniki, M; Nakamura, K

    1996-06-01

    Derivatives of chlorophyl, e.g. Fe-chlorin e6-Na, alpha, beta, gamma, delta-Tetraphenylporphine-tetrasulfonic acid disulfonic acid salt tetrahydrate (Fe-TPPTS) and alpha, beta, gamma, delta-Tetrakis (4-N-trimethylaminophenyl) porphine, tetra (p-toluensulfonate (Fe-TTMAPP), express SOD mimicking activity. Examination was made of suppressive effects of human cancer cell lines by derivatives of chlorophyl. Fe-TPPTS and Fe-TTMAPP suppressed proliferation of the human ovarian cancer cell lines but Fe-chlorin e6-Na failed to suppress the proliferation. Lipid peroxide was increased by application of Fe-TPPTS and Fe-TTMAPP, but decreased by application of Fe-chlorin e6-Na. SOD activity of the cancer cells did not change by application of these drugs. TPPTS and TTMAPP have a cationic charge but Fe-chlorin e6-Na has an anionic charge. It is suggested that charge of these drugs relates to the suppressive effects of the cancer cell proliferation. PMID:10851538

  9. Synthesis and Antiplatelet Aggregation Activity Evaluation of some 2-Aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine Derivatives.

    Esfahanizadeh, Marjan; Mohebbi, Shohreh; Dasht Bozorg, Behnam; Amidi, Salimeh; Gudarzi, Ali; Ayatollahi, Seyed Abdolmajid; Kobarfard, Farzad

    2015-01-01

    A series of novel 2-aminopyrimidine and 2-Substituted-4,6-diaminopyrimidine derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma using light transmission aggregometry. Among the tested derivatives, compounds Ia, Ib, IB and II16 exhibited the highest antiplatelet aggregation activity (36.75, 72.4, 62.5 and 80 µM). None of the compounds showed satisfactory activity against the aggregation induced by ADP but acceptable activities were observed against the aggregation induced by arachidonic acid. 2- aminopyrimidines were more active than 4,6- diaminopyrimidines in this respect. PMID:25901148

  10. Identification of a probiotic bacteria-derived activator of the aryl hydrocarbon receptor that inhibits colitis.

    Fukumoto, Suguru; Toshimitsu, Takayuki; Matsuoka, Shuji; Maruyama, Atsushi; Oh-Oka, Kyoko; Takamura, Takeyuki; Nakamura, Yuki; Ishimaru, Kayoko; Fujii-Kuriyama, Yoshiaki; Ikegami, Shuji; Itou, Hiroyuki; Nakao, Atsuhito

    2014-01-01

    The aryl hydrocarbon receptor (AhR) recognizes environmental xenobiotics and is originally thought to be involved in the metabolism (detoxification) of the substances. Recently, AhR is highlighted as an important regulator of inflammation. Notably, accumulating evidence suggests that activation of the AhR suppresses inflammatory bowel diseases (IBDs). Therefore, non-toxic AhR activators become attractive drug candidates for IBD. This study identified 1,4-dihydroxy-2-naphthoic acid (DHNA), a precursor of menaquinone (vitamin K2) abundantly produced by Propionibacterium freudenreichii ET-3 isolated from Swiss-type cheese, as an AhR activator. DHNA activated the AhR pathway in human intestinal epithelial cell line Caco2 cells and in the mouse intestine. Oral treatment of mice with DHNA induced anti-microbial proteins RegIIIβ and γ in the intestine, altered intestinal microbial flora and inhibited dextran sodium sulfate (DSS)-induced colitis, which recapitulated the phenotypes of AhR activation in the gut. As DHNA is commercially available in Japan as a prebiotic supplement without severe adverse effects, DHNA or its derivatives might become a promising drug candidate for IBD via AhR activation. The results also implicate that intestinal AhR might act not only as a sensor for xenobiotics in diet and water but also for commensal bacterial activity because DHNA is a precursor of vitamin K2 produced by vitamin K2-synthesizing commensal bacteria as well as propionic bacteria. Hence, DHNA might be a key bacterial metabolite in the host-microbe interaction to maintain intestinal microbial ecosystem. PMID:24518984

  11. A novel cold active esterase derived from Colombian high Andean forest soil metagenome.

    Jiménez, Diego Javier; Montaña, José Salvador; Alvarez, Diana; Baena, Sandra

    2012-01-01

    In order to search new lipolytic enzymes and conduct bioprospecting of microbial communities from high Andean forest soil, a metagenomic library of approximately 20,000 clones was constructed in Escherichia coli using plasmid p-Bluescript II SK+. The library covered 80 Mb of the metagenomic DNA mainly from Proteobacteria, Actinobacteria and Acidobacteria. Two clones with lipolytic activity in tributyrin as a substrate were recovered. Clone BAA3G2 (pSK-estGX1) was selected and the entire 4.6 Kb insert sequence was determined. The sequence had a GC content of 70.6% and could be derived from an undescribed Actinobacteria genome. One open reading frame encoded a polypeptide of 210 amino acids (gene estGX1) with a molecular mass of 22.4 kDa that contained the pentapeptide G-P-S-G-G near the N-terminus essential for lipase activity and the putative catalytic triad was identified, also a putative ribosomal binding site located 18 bp upstream the estGX1 ATG start codon was identified. The phylogenetic analysis suggested that the protein belonged to a new lipase family. The secreted enzyme showed a preference for short length fatty acids, with specific activity against p-nitrophenyl-butyrate (0.142 U/mg of total protein), it was cold active with relative activity of 30% at 10°C and moderately thermo active with relative activity of 80% at 50°C and had a pH optimum of 8.0 at 40°C. PMID:22806812

  12. Hydrophobic Effect of Amphiphilic Derivatives of Chitosan on the Antifungal Activity against Aspergillus flavus and Aspergillus parasiticus

    Vera Ap. de Oliveira Tiera

    2013-04-01

    Full Text Available Low molecular weight amphiphilic derivatives of chitosan were synthesized, characterized and their antifungal activities against Aspergillus flavus and Aspergillus parasiticus were tested. The derivatives were synthesized using as starting material a deacetylated chitosan sample in a two step process: the reaction with propyltrimethyl-ammonium bromide (Pr, followed by reductive amination with dodecyl aldehyde. Aiming to evaluate the effect of the hydrophobic modification of the derivatives on the antifungal activity against the pathogens, the degree of substitution (DS1 by Pr groups was kept constant and the proportion of dodecyl (Dod groups was varied from 7 to 29% (DS2. The derivatives were characterized by 1H-NMR and FTIR and their antifungal activities against the pathogens were tested by the radial growth of the colony and minimum inhibitory concentration (MIC methods. The derivatives substituted with only Pr groups exhibited modest inhibition against A. flavus and A. parasiticus, like that obtained with deacetylated chitosan. Results revealed that the amphiphilic derivatives grafted with Dod groups exhibited increasing inhibition indexes, depending on polymer concentration and hydrophobic content. At 0.6 g/L, all amphiphilic derivatives having from 7.0 to 29% of Dod groups completely inhibited fungal growth and the MIC values were found to decrease from 4.0 g/L for deacetylated chitosan to 0.25–0.50 g/L for the derivatives. These new derivatives open up the possibility of new applications and avenues to develop effective biofungicides based on chitosan.

  13. Synthesis and biological activity of substituted urea and thiourea derivatives containing 1,2,4-triazole moiety

    A series of novel thiourea and urea derivatives carrying 1,2,4-triazole moiety were synthesized and evaluated for their antifungal and larvicidal activity. Thiourea (1a-e) and urea derivatives (2a-e) were prepared by reacting 4-(aminophenyl)acetic acid with corresponding isothiocyanates and isocyana...

  14. Synthesis, Biological Evaluation and Structure-Activity Relationships of New Quinoxaline Derivatives as Anti-Plasmodium falciparum Agents

    Ana Gil

    2014-02-01

    Full Text Available We report the synthesis and antimalarial activities of eighteen quinoxaline and quinoxaline 1,4-di-N-oxide derivatives, eight of which are completely novel. Compounds 1a and 2a were the most active against Plasmodium falciparum strains. Structure-activity relationships demonstrated the importance of an enone moiety linked to the quinoxaline ring.

  15. Mechanism of action of ferrocene derivatives on the catalytic activity of topoisomerase IIalpha and beta--distinct mode of action of two derivatives.

    Sai Krishna, A D; Panda, Gayatri; Kondapi, Anand K

    2005-06-15

    Topoisomerase II is found to be present in two isoforms alpha and beta, and both the isoforms are regulated in cancerous tissue. Development of isoform-specific topoisomerase II poisons has been of great interest for cancer-specific drug targeting. In the present investigation using quantitative structure-activity analysis of ferrocene derivatives, we show that two derivatives of ferrocene, azalactone ferrocene and thiomorpholide amido methyl ferrocene, can preferentially inhibit topoisomerase IIbeta activity. Thiomorpholide amido methyl ferrocene shows higher inhibition of catalytic activity (IC(50) = 50 microM) against topoisomerase IIbeta compared to azalactone ferrocene (IC(50) = 100 microM). The analysis of protein DNA intermediates formed in the presence of these two compounds suggests that azalactone ferrocene readily induces formation of cleavable complex in a dose-dependent manner, in comparison with thiomorpholide amido methyl ferrocene. Both the compounds show significant inhibition of DNA-dependent ATPase activity of enzyme. These results suggest that azalactone ferrocene inhibits DNA passage activity of enzyme leading to the formation of cleavable complex, while thiomorpholide amido methyl ferrocene competes with ATP binding resulting in the inhibition of catalytic activity of enzyme. In summary, thiomorpholide amido methyl ferrocene and azalactone ferrocene show distinctly different mechanisms in inhibition of catalytic activity of topoisomerase IIbeta. PMID:15907782

  16. Antimutagenic activities of two suspected anticarcinogenic bifunctional organoiron seleno-terephthalate derivatives.

    Maslat, Ahmed O; Jibril, Ibrahim; Mizyed, Shehdeh

    2010-07-01

    Two newly bifunctional organoiron seleno-terephthalate derivatives (S1 and S2) were synthesized as potential anticarcinogenic compounds. In a previous study, they were found to have antibacterial and/or antifungal activity, while they did not show any mutagenic action. Such compounds were investigated in the present study for their antimutagenic activity. Sodium azide, hydrogen peroxide, and 4-nitro-o-phenylenediamine, as known mutagens for strains TA100, TA102, and TA98 of Salmonella typhimurium, respectively, were used. Both (S1 and S2) compounds showed a strong antimutagenic action of >98% against sodium azide, >70% against hydrogen peroxide, and >65% activity against 4-nitro-o-phenylenediamine. Bearing in mind the strong correlation between mutagenicity and carcinogenicity, the above compounds can be considered as potentially promising anticarcinogens. Therefore, the present results are very encouraging to investigate the above compounds for other biological activities, including their evaluation as anticarcinogens. A suggested mechanism for the antimutagenicity of the tested compounds is presented. PMID:20462347

  17. Metal based isatin-derived sulfonamides: their synthesis, characterization, coordination behavior and biological activity.

    Chohan, Zahid H; Supuran, Claudiu T; Ben Hadda, Taibi; Nasim, Faiz-Ul-Hassan; Khan, Khalid M

    2009-06-01

    Some isatin derived sulfonamides and their transition metal [Co(II), Cu(II), Ni(II), Zn(II)] complexes have been synthesized and characterized. The structure of synthesized compounds and their nature of bonding have been inferred on the basis of their physical (magnetic susceptibility and conductivity measurements), analytical (elemental analyses) and spectral (IR, (1)H NMR and (13)C NMR) properties. An octahedral geometry has been suggested for Co(II), Ni(II) and Zn(II) and square-planar for Cu(II) complexes. In order to assess the antibacterial and antifungal behavior, the ligands and their metal(II) complexes were screened for their in vitro antibacterial activity against four Gram-negative species, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi and two Gram-positive species, Staphylococcus aureus and Bacillus subtilis and, for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. In vitro cytotoxic properties of all the compounds were also studied against Artemia salina by brine shrimp bioassay. The results of average antibacterial/antifungal activity showed that zinc(II) complexes were found to be the most active against one or more bacterial/fungal strains as compared to the other metal complexes. PMID:18825557

  18. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives.

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric acid), an aromatic aldehyde and urea or thiourea in the presence of nanoporous silica SBA-Pr-SO3H under solvent free conditions. Urease inhibitory activity of spiro compounds were tested against Jack bean urease using Berthelot alkaline phenol-hypochlorite method. Five of 13 compounds were inhibitor and two of them were enzyme activators. Analysis of the docking results showed that, in most of the spiro molecules, one of the carbonyl groups is coordinated with both nickel atoms, while the other one is involved in the formation of hydrogen bonds with important active-site residues. The effect of inserting two methyl groups on N atoms of barbiturate ring, S substituted, ortho, meta and para substituted compounds were investigated too. PMID:26664377

  19. Antibacterial and antifungal activity of zinc(II complexes with some 2-methylbenzimidazole derivatives

    Podunavac-Kuzmanović Sanja O.

    2005-01-01

    Full Text Available Zinc(II chloride reacts with 2-methylbenzimidazole derivatives to give complexes of the formula ZnL2Cl2-nH2O, where L=2-methylbenzimidazole l-benzyl-2-methylbenzimida-zole and l-(4-methylbenzyl-2-methylbenzimidazole n=0, 0.5 or 1. All the ligands and their zinc(II complexes were evaluated for their in vitro antimicrobial activity against Pseudomonas aeruginosa Bacillus sp., Staphylococcus aureus, Sarcina lutea and Candida pseudotropicalis. It was found that the majority of the investigated compounds displayed in vitro antimicrobial activity against very persistent microorganisms, except for the starting ligand, 2-methylbenzimidazole and its zinc(II complex which were active only against gram-negative bacteria. None of the compounds was significantly effective against Candida pseudotropicalis, except for l-(4-methylbenzyl-2-methylbenzimidazoleandits complex, which very slightly or slightly inhibited the yeast growth. The minimum inhibitory concentration (MIC was determined for all the ligands and their complexes. The effect of ligand and complex structure on the antimicrobial activity was discussed.

  20. Plant-Derived Tick Repellents Activate the Honey Bee Ectoparasitic Mite TRPA1.

    Peng, Guangda; Kashio, Makiko; Morimoto, Tomomi; Li, Tianbang; Zhu, Jingting; Tominaga, Makoto; Kadowaki, Tatsuhiko

    2015-07-14

    We have identified and characterized the TRPA1 channel of Varroa destructor (VdTRPA1), a major ectoparasitic mite of honey bee. One of the two VdTRPA1 isoforms, VdTRPA1L, was activated by a variety of plant-derived compounds, including electrophilic compounds, suggesting that chemical activation profiles are mostly shared between arthropod TRPA1 channels. Nevertheless, carvacrol and α-terpineol activated VdTRPA1L but not a honey bee noxious-stimuli-sensitive TRPA, AmHsTRPA, and Drosophila melanogaster TRPA1. Activation of VdTRPA1L in D. melanogaster taste neurons by the above compounds was sufficient to modify the gustatory behaviors. Carvacrol and α-terpineol repelled V. destructor in a laboratory assay, and α-terpineol repressed V. destructor entry for reproduction into the brood cells in hives. Understanding the functions of parasite TRP channels not only gives clues about the evolving molecular and cellular mechanisms of parasitism but also helps in the development of control methods. PMID:26146083

  1. Plant-Derived Tick Repellents Activate the Honey Bee Ectoparasitic Mite TRPA1

    Guangda Peng

    2015-07-01

    Full Text Available We have identified and characterized the TRPA1 channel of Varroa destructor (VdTRPA1, a major ectoparasitic mite of honey bee. One of the two VdTRPA1 isoforms, VdTRPA1L, was activated by a variety of plant-derived compounds, including electrophilic compounds, suggesting that chemical activation profiles are mostly shared between arthropod TRPA1 channels. Nevertheless, carvacrol and α-terpineol activated VdTRPA1L but not a honey bee noxious-stimuli-sensitive TRPA, AmHsTRPA, and Drosophila melanogaster TRPA1. Activation of VdTRPA1L in D. melanogaster taste neurons by the above compounds was sufficient to modify the gustatory behaviors. Carvacrol and α-terpineol repelled V. destructor in a laboratory assay, and α-terpineol repressed V. destructor entry for reproduction into the brood cells in hives. Understanding the functions of parasite TRP channels not only gives clues about the evolving molecular and cellular mechanisms of parasitism but also helps in the development of control methods.

  2. Inhibitory activity of the peptides derived from buffalo prolactin on angiogenesis

    Jaeok Lee; Syamantak Majumder; Suvro Chatterjee; Kambadur Muralidhar

    2011-06-01

    The peptide fragments obtained by cathepsin digestion of purified buffalo prolactin (buPRL) monomer have been characterized using SDS-PAGE and FPLC with regard to size and pI. Their antiangiogenic activity was tested in chick embryo chorioallantoic membrane (CAM) assay and the human endothelial cells wound healing assay. Antiangiogenic activity was observed in cathepsin-cleaved fragments from buPRL. Further, a peptide sequence 45A-46Q-47G-48K-49G-50F-51I-52T-53M-54A-55L-56N-57S-58C, which matched with human somatostatin (hSST), a known antiangiogenic factor, was located in the second loop between the first and second α-helices in the threedimensional structure of buPRL, obtained by homology modelling. The synthetic peptide matching with SST sequence was found to exhibit antiangiogenic activity in both in vitro and ex vivo assays. It was also observed that all the peptides related to buPRL could antagonize the vascular endothelial growth factor (VEGF) and bradykinin (BK)-dependent production of endothelial nitric oxide (NO), which is a pre-requisite for endothelial tube formation. It is concluded therefore that an internal sequence in buPRL and peptide fragments derived from cathepsin-digested buPRL exhibit antiangiogenic activities.

  3. Synthesis, Activity, and Docking Study of Novel Phenylthiazole-Carboxamido Acid Derivatives as FFA2 Agonists.

    Ma, Liang; Wang, Taijin; Shi, Min; Fu, Ping; Pei, Heying; Ye, Haoyu

    2016-07-01

    Free fatty acid receptor 2 (FFA2), also known as GPR43, is activated by short-chain fatty acids (SCFAs) that are mainly produced by the gut microbiota through the fermentation of undigested carbohydrates and dietary fibers. FFA2 currently appears to be a potential target in the management of obesity, diabetes, inflammatory diseases, and cancer. In the study, a series of novel phenylthiazole-carboxamido acid derivatives has been synthesized and evaluated as potential orthosteric FFA2 ligands for the study of structure-activity relationships. Compound 6e was found to exhibit the twofold potent agonistic activity in the stable hFFA2-transfected CHO-K1 cells (EC50 = 23.1 μm) as that of positive control propionate (EC50 = 43.3 μm). We also reported the results of mutagenesis studies based on the crystal structure of hFFA1 bound to TAK-875 at 2.3 Å resolution to identify important residues for orthosteric agonist 6e inducing FFA2 activation. PMID:26808470

  4. Cobalt-Nickel-Boron Supported over Polypyrrole-Derived Activated Carbon for Hydrolysis of Ammonia Borane

    Yongjin Zou

    2016-07-01

    Full Text Available In this study, polypyrrole (PPy nanofibers were used to synthesize a super-activated carbon material. A highly-dispersed Co-Ni-B catalyst was supported on PPy nanofiber-derived activated carbon (PAC by chemical reduction. The Co-Ni-B/PAC hybrid catalyst exhibited excellent catalytic performance for the decomposition of ammonia borane (AB in an aqueous alkaline solution at room temperature. The size of the metal particles, morphology of Co-Ni-B/PAC, and catalytic activity of the supported catalyst were investigated. Ni-B, Co-B, and Co-Ni-B catalysts were also synthesized in the absence of PAC under similar conditions for comparison. The maximum hydrogen generation rate (1451.2 mL−1·min−1·g−1 at 25 °C was obtained with Co-Ni-B/PAC. Kinetic studies indicated that the hydrolysis reaction of AB was first order with respect to Co-Ni-B/PAC, and the activation energy was 30.2 kJ·mol−1. Even after ten recycling experiments, the catalyst showed good stability owing to the synergistic effect of Co-Ni-B and PAC.

  5. Antioxidative and radioprotective activities of semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1.

    Kumar, Raj; Bansal, Deen Dayal; Patel, Dev Dutt; Mishra, Saurabh; Karamalakova, Yana; Zheleva, A; Gadjeva, Vessilina; Sharma, Rakesh Kumar

    2011-03-01

    A semiquinone glucoside derivative (SQGD) was isolated from a radioresistant bacterium Bacillus sp. INM-1 and its antioxidant and radioprotective activities were evaluated using in vitro assays. Natural stable free radical properties of SQGD in solid as well as in solution form were estimated using Electron Paramagnetic Resonance (EPR) spectrometry. Results of the study were demonstrated high reducing power (1.267 ± 0.03356 U(abs)) and nitric oxide radicals scavenging activity (34.684 ± 2.132%) of SQGD. Maximum lipid peroxidation inhibitory activity of SQGD was found to be 74.09 ± 0.08% at 500 μg/ml concentration. Similarly, significant (39.54%; P EPR spectroscopic analysis of the SQGD indicated ~80% reduction of DPPH radicals at 6.4% concentration. EPR spectral analysis of SQGD was revealed an appearance of very strong EPR signal of 2.00485 (crystalline form) and 2.00520 (solution form) g(y) tensor value, which were an established characteristic of o-semiquinone radicals. Therefore, it can be concluded that SQGD is a natural stable o-semiquinone-type radical, possessing strong antioxidant activities and can effectively neutralize radiation induced free radicals in biological system. PMID:21116688

  6. A potential plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis

    6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses...

  7. Synthesis of 6-sulfamoyl-4-oxoquinoline-3-carboxylic acid derivatives as integrase antagonists with anti-HIV activity

    Zai Gang Luo; Cheng Chu Zeng; Lei Fu Yang; Hong Qiu He; Cun Xin Wang; Li Ming Hu

    2009-01-01

    A series of novel 6-sulfamoyl-4-oxoquinoline-3-earboxylic acids derivatives have been synthesized and screened for HIV integrase inhibition activity. Their structures were confirmed by ESI-MS, 1H NMR and 13C NMR.

  8. Tracking small mountainous river derived terrestrial organic carbon across the active margin marine environment

    Childress, L. B.; Blair, N. E.; Orpin, A. R.

    2015-12-01

    Active margins are particularly efficient in the burial of organic carbon due to the close proximity of highland sources to marine sediment sinks and high sediment transport rates. Compared with passive margins, active margins are dominated by small mountainous river systems, and play a unique role in marine and global carbon cycles. Small mountainous rivers drain only approximately 20% of land, but deliver approximately 40% of the fluvial sediment to the global ocean. Unlike large passive margin systems where riverine organic carbon is efficiently incinerated on continental shelves, small mountainous river dominated systems are highly effective in the burial and preservation of organic carbon due to the rapid and episodic delivery of organic carbon sourced from vegetation, soil, and rock. To investigate the erosion, transport, and burial of organic carbon in active margin small mountainous river systems we use the Waipaoa River, New Zealand. The Waipaoa River, and adjacent marine depositional environment, is a system of interest due to a large sediment yield (6800 tons km-2 yr-1) and extensive characterization. Previous studies have considered the biogeochemistry of the watershed and tracked the transport of terrestrially derived sediment and organics to the continental shelf and slope by biogeochemical proxies including stable carbon isotopes, lignin phenols, n-alkanes, and n-fatty acids. In this work we expand the spatial extent of investigation to include deep sea sediments of the Hikurangi Trough. Located in approximately 3000 m water depth 120 km from the mouth of the Waipaoa River, the Hikurangi Trough is the southern extension of the Tonga-Kermadec-Hikurangi subduction system. Piston core sediments collected by the National Institute of Water and Atmospheric Research (NIWA, NZ) in the Hikurangi Trough indicate the presence of terrestrially derived material (lignin phenols), and suggest a continuum of deposition, resuspension, and transport across the margin

  9. Melanoma-derived factors alter the maturation and activation of differentiated tissue-resident dendritic cells.

    Hargadon, Kristian M; Bishop, Johnathan D; Brandt, John P; Hand, Zachary C; Ararso, Yonathan T; Forrest, Osric A

    2016-01-01

    Dendritic cells (DCs) are key regulators of host immunity that are capable of inducing either immune tolerance or activation. In addition to their well-characterized role in shaping immune responses to foreign pathogens, DCs are also known to be critical for the induction and maintenance of anti-tumor immune responses. Therefore, it is important to understand how tumors influence the function of DCs and the quality of immune responses they elicit. Although the majority of studies in this field to date have utilized either immortalized DC lines or DC populations that have been generated under artificial conditions from hematopoietic precursors in vitro, we wished to investigate how tumors impact the function of already differentiated, tissue-resident DCs. Therefore, we used both an ex vivo and in vivo model system to assess the influence of melanoma-derived factors on DC maturation and activation. In ex vivo studies with freshly isolated splenic DCs, we demonstrate that the extent to which DC maturation and activation are altered by these factors correlates with melanoma tumorigenicity, and we identify partial roles for tumor-derived transforming growth factor (TGF)β1 and vascular endothelial growth factor (VEGF)-A in the altered functionality of DCs. In vivo studies using a lung metastasis model of melanoma also demonstrate tumorigenicity-dependent alterations to the function of lung-resident DCs, and skewed production of proinflammatory cytokines and chemokines by these tumor-altered cells is associated with recruitment of an immune infiltrate that may ultimately favor tumor immune escape and outgrowth. PMID:26010746

  10. Synthesis and herbicidal activity evaluation of novel α-amino phosphonate derivatives containing a uracil moiety.

    Che, Jian-yi; Xu, Xiao-yun; Tang, Zi-long; Gu, Yu-cheng; Shi, De-qing

    2016-02-15

    A series of novel α-amino phosphonate derivatives containing a uracil moiety 3a-3l were designed and synthesized by a Lewis acid (magnesium perchlorate) catalyzed the Kabachnik-Fields reaction. The bioassays {in vitro, in vivo [Glass House 1 (GH1) and Glass House 2 (GH2)]} showed that most of compounds 3 exhibited excellent and selective herbicidal activities; for example, in GH1 test, compounds 3b, 3d, 3f, 3h and 3j showed excellent and wide spectrum herbicidal activities at the dose of 1000 g/ha, and compounds 3b and 3j exhibited 100% inhibition activities against the four plants in both post- and pre-emergence treatments. Moreover, most of compounds 3 showed higher inhibition against Amaranthus retroflexus and Digitaria sanguinalis than Glyphosate did in pre-emergence treatment. In GH2 test, the four compounds (3b, 3d, 3h and 3j) exhibited 100% inhibition against Solanum nigrum, Amaranthus retroflexus and Ipomoea hederacea in post-emergence treatment and displayed 100% inhibition against Solanum nigrum, Amaranthus retroflexus in pre-emergence treatment at the rate of 250 g/ha, and compound 3b showed the best and broad spectrum herbicidal activities against the six test plants. However, the four compounds displayed weaker herbicidal activities against Lolium perenne and Echinochloa crus-galli than the other four plants at the rate of 250 g/ha in both pre- and post-emergence treatments. So, compounds 3 can be used as a lead compound for further structure optimization for developing potential selective herbicidal agent. Their preliminary structure-activity relationships were also investigated. PMID:26786699

  11. Extracellular matrix is a source of mitogenically active platelet-derived growth factor.

    Field, S L; Khachigian, L M; Sleigh, M J; Yang, G; Vandermark, S E; Hogg, P J; Chesterman, C N

    1996-08-01

    Platelet-derived growth factor (PDGF) is a chemotactic and mitogenic agent for fibroblasts and smooth muscle cells and plays a key role in the development of atherosclerotic lesions. PDGF is produced by a number of normal and transformed cell types and occurs as homo- or heterodimers of A and B polypeptide chains. Using Chinese hamster ovary (CHO) cells transfected with various forms of PDGF, we have previously shown that PDGF A(s) (short splice version) is secreted, PDGF A(l) (long splice version) predominantly extracellular matrix-associated, and PDGF B divided between medium, cells, and matrix. In the present study we have demonstrated the mitogenic activity of matrix-localized PDGF in artificial and more physiologically relevant models by culturing Balb/c-3T3 cells (3T3), human foreskin fibroblasts (HFF), and rabbit aortic smooth muscle cells (SMC) on extracellular matrix (ECM) laid down by PDGF-expressing CHO cells and human umbilical vein endothelial cells (HUVEC). These cells responded to the local growth stimulus of PDGF-containing CHO ECM and HUVEC ECM. We showed that 3T3 cells required proteolytic activity to utilize matrix-localized PDGF, as aprotinin and epsilon-ACA inhibited growth and 3T3 cells were shown to possess plasminogen activator activity. HFF and SMC did not appear to require proteolytic activity (including metalloproteinase and serine protease activity) as a prerequisite for mitogenesis but were able to access immobilized PDGF by contact with the matrix. An understanding of the mechanisms whereby the utilization of stored PDGF is controlled in situations of excessive cellular proliferation will aid in the development of therapy for these conditions. PMID:8707868

  12. A newly synthesized sinapic acid derivative inhibits endothelial activation in vitro and in vivo.

    Zeng, Xiaoyun; Zheng, Jinhong; Fu, Chenglai; Su, Hang; Sun, Xiaoli; Zhang, Xuesi; Hou, Yingjian; Zhu, Yi

    2013-05-01

    Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation. Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity. We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease. We designed and synthesized 10 SA derivatives according to their chemical structures. Preliminary screening of the compounds involved scavenging hydroxyl radicals and 2,2-diphenyl-1-picrylhydrazyl (DPPH(⋅)), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs. 1-Acetyl-sinapic acyl-4-(3'-chlorine-)benzylpiperazine (SA9) had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo. Thus, the effect of SA9 was further studied. SA9 inhibited tumor necrosis factor α-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs. In vivo, result of face-to-face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule-1 in mouse aortic intima. To study the molecular mechanism, results from luciferase assay, nuclear translocation of NF-κB, and Western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-κB activation in ECs. SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs. It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders. PMID:23470287

  13. New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity

    Gholamreza Karimipour

    2015-06-01

    Full Text Available This work studied the synthesis of 5,10,15-tris(4-aminophenyl-20-(N,N-dialkyl/diaryl-N-phenylurea porphyrins (P1-P4 with alkyl or aryl groups of Ph, iPr, Et and Me, respectively and also the preparation of their manganese (III and cobalt (II complexes (MnP and CoP. The P1-P4 ligands were characterized by different spectroscopic techniques (1H NMR, FTIR, UV-Vis and elemental analysis, and metalated with Mn and Co acetate salts. The antibacterial and antifungal activities of these compounds in vitro were investigated by agar-disc diffusion method against Escherichia coli (-, Pseudomonas aeruginosa (-, Staphylococcus aureus(+, Bacillus subtilis (+ and Aspergillus oryzae and Candida albicans. Results showed that antibacterial and antifungal activity of the test samples increased with increase of their concentrations and the highest activity was obtained when the concentration of porphyrin compounds was 100 µg/mL. The activity for the porphyrin ligands depended on the nature of the urea derivative substituents and increased in the order P1 > P2 > P3 >P4, which was consistent with the order of their liposolubility. MnP and CoP complexes exhibited much higher antibacterial and antifungal activity than P1-P4ligands. Further, the growth inhibitory effects of these compounds was generally in the order CoP complexes > MnP complexes > P1-P4 ligands. Among these porphyrin compounds, CoP1displayed the highest antibacterial and antifungal activity, especially with a concentration of 100 µg/mL, against all the four tested bacteria and two fungi, and therefore it could be potential to be used as drug.

  14. Multiobjective optimization in quantitative structure-activity relationships: deriving accurate and interpretable QSARs.

    Nicolotti, Orazio; Gillet, Valerie J; Fleming, Peter J; Green, Darren V S

    2002-11-01

    Deriving quantitative structure-activity relationship (QSAR) models that are accurate, reliable, and easily interpretable is a difficult task. In this study, two new methods have been developed that aim to find useful QSAR models that represent an appropriate balance between model accuracy and complexity. Both methods are based on genetic programming (GP). The first method, referred to as genetic QSAR (or GPQSAR), uses a penalty function to control model complexity. GPQSAR is designed to derive a single linear model that represents an appropriate balance between the variance and the number of descriptors selected for the model. The second method, referred to as multiobjective genetic QSAR (MoQSAR), is based on multiobjective GP and represents a new way of thinking of QSAR. Specifically, QSAR is considered as a multiobjective optimization problem that comprises a number of competitive objectives. Typical objectives include model fitting, the total number of terms, and the occurrence of nonlinear terms. MoQSAR results in a family of equivalent QSAR models where each QSAR represents a different tradeoff in the objectives. A practical consideration often overlooked in QSAR studies is the need for the model to promote an understanding of the biochemical response under investigation. To accomplish this, chemically intuitive descriptors are needed but do not always give rise to statistically robust models. This problem is addressed by the addition of a further objective, called chemical desirability, that aims to reward models that consist of descriptors that are easily interpretable by chemists. GPQSAR and MoQSAR have been tested on various data sets including the Selwood data set and two different solubility data sets. The study demonstrates that the MoQSAR method is able to find models that are at least as good as models derived using standard statistical approaches and also yields models that allow a medicinal chemist to trade statistical robustness for chemical

  15. Sorption of mercury onto waste material derived low-cost activated carbon

    Bhakta, Jatindra N.; Rana, Sukanta; Lahiri, Susmita; Munekage, Yukihiro

    2014-11-01

    The present study was performed to develop the low-cost activated carbon (AC) from some waste materials as potential mercury (Hg) sorbent to remove high amount of Hg from aqueous phase. The ACs were prepared from banana peel, orange peel, cotton fiber and paper wastes by pyrolysis and characterized by analyzing physico-chemical properties and Hg sorption capacity. The Brunauer Emmett and Teller surface areas (cotton 138 m2/g; paper 119 m2/g), micropore surface areas (cotton 65 m2/g; paper 54 m2/g) and major constituent carbon contents (cotton 95.04 %; paper 94.4 %) were higher in ACs of cotton fiber and paper wastes than the rest two ACs. The Hg sorption capacities and removal percentages were greater in cotton and paper wastes-derived ACs compared to those of the banana and orange peels. The results revealed that elevated Hg removal ability of cotton and paper wastes-derived ACs is largely regulated by their surface area, porosity and carbon content properties. Therefore, ACs of cotton and paper wastes were identified as potential sorbent among four developed ACs to remove high amount of Hg from aqueous phase. Furthermore, easily accessible precursor material, simple preparation process, favorable physico-chemical properties and high Hg sorption capacity indicated that cotton and paper wastes-derived ACs could be used as potential and low-cost sorbents of Hg for applying in practical field to control the severe effect of Hg contamination in the aquatic environment to avoid its human and environmental health risks.

  16. Fuel derived pollutants and boating activity patterns in the Sea of Galilee.

    Dinerman, Efrat; Dubowski, Yael; Friedler, Eran

    2011-11-01

    MTBE (Methyl tert-Butyl Ether) is a fuel additive that replaced lead as an antiknock compound in internal combustion motors. Few years after its introduction, detectable levels of MTBE were found in various water bodies. MTBE has a very low taste and odor threshold and is a potential carcinogen. Another group of fuel derived toxic compounds that has been detected in water bodies is BTEX (Benzene, Toluene, Ethylbenzene and Xylene). Boating activity and allochthonous contributions from watersheds are the major sources of fuel derived pollutants in lakes. Their concentrations in lakes thus vary as a function of boating activity intensity, lake surface area and depth, weather and wind regime, land-use in the watershed, etc. The Sea of Galilee (Lake Kinneret) is the only recreational lake in Israel and an important freshwater source. In the current study, a sampling campaign was conducted in order to quantify MTBE and BTEX concentrations in Lake Kinneret, its marinas and its main contributing streams. In addition, a boating-use survey was performed in order to estimate MTBE and BTEX contribution of recreational boating. The sampling campaign revealed that, as expected, MTBE concentrations were higher than BTEX, and that near shore (i.e., marina) concentrations were higher than in-lake concentrations. Despite the clear contribution from boating, high MTBE concentrations were found following a major inflow event in winter, indicating the importance of the allochthonous contribution. The contribution from boating during summer, as measured indirectly by in-lake concentrations, is likely underestimated due to enhanced MTBE volatilization due to strong winds and high temperatures. May-September was found to be the main recreational boating season, with continued boating year round. On average, a single boat is active 23 d/y, with 84% of the watercrafts being active only during weekends and holidays. The survey further indicated that boats stay in the lake for 4.5 h on

  17. Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury

    Shixin Liu

    2015-02-01

    Full Text Available In this work, we designed and synthesized a series of amide derivatives (1–13, benzoxazine derivatives (16–28 and amino derivatives (29–30 from xyloketal B. All 28 new derivatives and seven known compounds (14, 15, 31–35 were evaluated for their protection against H2O2-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC50 values of them and the leading compound 31 (xyloketal B were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B were further to examine in the JC-1 mitochondrial membrane potential (MMP assay of HUVECs using flow cytometry (FCM. The result indicated that 23 and 24 significantly inhibited H2O2-induced decrease of the cell mitochondrial membrane potential (ΔΨm at 25 μM. Collectively, the protective effects of xyloketals on H2O2-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP.

  18. Nanobionics of Pharmacologically Active Derivatives of Fullerene C{sub 60}

    Kotelnikova, R.A., E-mail: kotel@icp.ac.ru; Bogdanov, G.N.; Frog, E.C.; Kotelnikov, A.I.; Shtolko, V.N. [Institute of Problems of Chemical Physics RAS, Chernogolovka (Russian Federation); Romanova, V.S. [Institute of Organoelement Compounds RAS (Russian Federation); Andreev, S.M. [NRC Institute of Immunology (Russian Federation); Kushch, A.A; Fedorova, N.E.; Medzhidova, A.A. [Ivanovski Institute of Virology RAMS (Russian Federation); Miller, G.G. [Institute of Epidemiology and Microbiology RAMS (Russian Federation)

    2003-12-15

    The physical-chemical mechanisms of pharmacologic functioning of amino acid derivatives of fullerene C{sub 60} (ADF) have been studied. ADF were shown to penetrate through the lipid bilayer of liposomes without destruction of membrane integrity. ADF are able to carry bivalent metal ions through phospholipid bilayer owing to the formation of complexes. It was shown that stereoisomers of ADF selectively penetrate into phospholipid membranes. In contrast to D-isomers, L-isomers penetrate through the phosphatidylcholine membrane into liposome interior. Stereo-specific effect of ADF enantiomers was also observed in reaction of peroxidation of lipids. Besides that, ADF bring about a substantial increase in the catalytic activity of monoaminoxidases A and B. The directed intraprotein electron transfer was studied by creating a donor-acceptor pair in a water solution in the presence of ADF. To realize the intraprotein electron transfer, the model system was produced on the base of apomyoglobin by incorporating ADF (electron acceptor) into the heme pocket of protein instead of removed heme. It was established that the fullerene C{sub 60} and its derivatives did not produce specific anti-C{sub 60} antibodies, both IgG and IgE classes, while ADF themselves are efficient adjuvants, i.e. they increased the antibody response to poor antigens. Some ADF were found to inhibit the human immunodeficiency virus and human cytomegalovirus infection.

  19. Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana

    Ze Tian; Geng Lin; Rui-Xia Zheng; Feng Huang; Meng-Su Yang; Pei-Gen Xiao

    2006-01-01

    AIM: To investigate the anti-tumor activity of ursolic acid (UA) and its derivatives isolated from Aralia decaisneana on hepatocellular carcinoma both in vitro andin vivo.METHODS: In vivo cytotoxicity was first screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, DNA ladder, flow cytometry analysis, Western blot and real time PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H22 was used to evaluate the growth inhibitory effect of UA in vivo.RESULTS: UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells,but had no inhibitory effect on primarily cultured normal mouse hepatocytes whereas all the six derivatives of UA could not inhibit the growth of all tested cell lines. Further study on mechanism demonstrated that apoptosis and G0/G1 arrest were involved in the cytotoxicity and cleavage of poly-(ADP-ribose)-polymerase (PARP). Downregulation of cyclooxygenase-2(COX-2) protein and upregulation of heat shock protein (HSP) 105 mRNA correlated to the apoptosis of HepG2cells treated with UA. In addition, UA also could inhibit the growth of H22 hepatoma in vivo.CONCLUSION: UA is a promising anti-tumor agent, but further work needs to be done to improve its solubility.

  20. Efficient synthesis and activity of beneficial intestinal flora of two lactulose-derived oligosaccharides.

    Zhu, Zhen-Yuan; Cui, Di; Gao, Hui; Dong, Feng-Ying; Liu, Xiao-Cui; Liu, Fei; Chen, Lu; Zhang, Yong-Min

    2016-05-23

    Lactulose is considered as a prebiotic because it promotes the intestinal proliferation of Lactobacillus acidophilus which is added to various milk products. Moreover, lactulose is used in pharmaceuticals as a gentle laxative and to treat hyperammonemia. This study was aimed at the total synthesis of two Lactulose-derived oligosaccharides: one is 3-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,3-glycosidic bound, the other is 1-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,1-glycosidic bound, which were accomplished in seven steps from d-fructose and β-d-galactose and every step of yield above 75%. This synthetic route provided a practical and effective synthetic strategy for galactooligosaccharides, starting from commercially available monosaccharides. Then we evaluated on their prebiotic properties in the search for potential agents of regulating and improving the intestinal flora of human. The result showed that the prebiotic properties of Lactulose-derived oligosaccharides was much better than Lactulose. Among them, 3-O-β-d-galactopyranosyl-d-fructose displayed the most potent activity of proliferation of L. acidophilus. PMID:26974370