The formation mechanism of lactones in Gouda cheese

NARCIS (Netherlands)

Alewijn, M.; Smit, B.; Sliwinski, E.L.; Wouters, J.T.M.

2007-01-01

Lactones are fat-derived aroma compounds, but the formation mechanism of these compounds during ripening of Gouda cheese is unknown. Both enzymatic and chemical formation pathways were investigated in this study. Lactone formation from milk triglycerides or free fatty acids by lactic acid bacteria

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

Science.gov (United States)

Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Development of an in vitro bioassay for measuring susceptibility to macrocyclic lactone anthelmintics in Dirofilaria immitis.

Science.gov (United States)

Evans, Christopher C; Moorhead, Andrew R; Storey, Bobby E; Wolstenholme, Adrian J; Kaplan, Ray M

2013-12-01

For more than 20 years, anthelmintics of the macrocyclic lactone (ML) drug class have been widely and effectively used as preventives against the canine heartworm, Dirofilaria immitis. However, in recent years an increased number of lack of efficacy (LOE) cases are being reported, in which dogs develop mature heartworm infections despite receiving monthly prophylactic doses of ML drugs. While this situation is raising concerns that heartworms may be developing resistance to MLs, compelling evidence for this is still lacking. Resolution of this dilemma requires validated biological or molecular diagnostic assays, but, unfortunately, no such tests currently exist. To address this need, we developed and optimized a larval migration inhibition assay (LMIA) for use with D. immitis third-stage larvae. The LMIA was used to measure the in vitro dose-response of two ML drugs (ivermectin and eprinomectin) on a known ML-susceptible laboratory strain of D. immitis. A nonlinear regression model was fit to the dose-response data, from which IC50 values were calculated; the mean IC50 and 95% confidence interval for IVM was 4.56 μM (1.26-16.4 μM), greater than that for EPR at 2.02 μM (1.68-2.42 μM), and this difference was significant (p = 0.0428). The R (2) value for EPR assays (0.90) was also greater than that for IVM treatment (0.71). The consistency and reproducibility of the dose-response data obtained with this assay suggests that it may be a useful technique for investigating the relative susceptibilities to ML drugs in other D. immitis populations.

Synthesis of novel symmetrical macrocycle via oxidative homocoupling of bisalkyne

Energy Technology Data Exchange (ETDEWEB)

Kamalulazmy, Nurulain; Hassan, Nurul Izzaty [School of Chemical Sciences and Food Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan (Malaysia)

2014-09-03

A novel symmetrical macrocycle has been synthesised via oxidative homocoupling of bisalkyne, diprop-2-ynyl pyridine-2,6-dicarboxylate mediated by copper (I) iodide (CuI) and 4-dimethylaminopyridine (DMAP). The precursor compound was synthesised from 2,6-pyridine dicarbonyl dichloride and propargyl alcohol in the presence of triethylamine. The reaction mixture was stirred overnight and further purified via column chromatograpy with 76% yield. Single crystal for X-ray study was obtained by recrystallization from acetone. Subsequently, a symmetrical macrocycle was synthesised from oxidative homocoupling of precursor compound in open atmosphere. The crude product was purified by column chromatography to furnish macrocycle compound with 5% yield. Both compounds were characterised by IR, {sup 1}H and {sup 13}C NMR and mass spectral techniques. The unusual conformation of the bisalkyne and twisted conformation of designed macrocycle has influence the percentage yield. This has been studied thoroughly by X-ray crystallography and electronic structure calculations.

Comprehensive computational design of ordered peptide macrocycles

Science.gov (United States)

Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fátima; Rettie, Stephen A.; Kim, David E.; Silva, Daniel-Adriano; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

2018-01-01

Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and D-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. PMID:29242347

Evaluation of the larval migration inhibition assay for detecting macrocyclic lactone resistance in Dirofilaria immitis.

Science.gov (United States)

Evans, Christopher C; Moorhead, Andrew R; Storey, Bobby E; Blagburn, Byron L; Wolstenholme, Adrian J; Kaplan, Ray M

2017-11-15

Anthelmintics of the macrocyclic lactone (ML) drug class are widely used as preventives against the canine heartworm (Dirofilaria immitis). Over the past several years, however, reports of ML lack of efficacy (LOE) have emerged, in which dogs develop mature heartworm infection despite the administration of monthly prophylactics. More recently, isolates from LOE cases have been used to infect laboratory dogs and the resistant phenotype has been confirmed by the establishment of adult worms in the face of ML treatment at normally preventive dosages. Testing for and monitoring resistance in D. immitis requires a validated biological or molecular diagnostic assay. In this study, we assessed a larval migration inhibition assay (LMIA) that we previously optimized for use with D. immitis third-stage larvae (L 3 ). We used this assay to measure the in vitro ML susceptibilities of a known-susceptible laboratory strain of D. immitis and three highly suspected ML-resistant isolates originating from three separate LOE cases; progeny from two of these isolates have been confirmed ML-resistant by treatment of an infected dog in a controlled setting. A nonlinear regression model was fit to the dose-response data, from which IC 50 values were calculated. The D. immitis LMIA yielded consistent and reproducible dose-response data; however, no statistically significant differences in drug susceptibility were observed between control and LOE parasites. Additionally, the drug concentrations needed to paralyze the L 3 were much higher than those third- and fourth-stage larvae would experience in vivo. IC 50 values ranged from 1.57 to 5.56μM (p≥0.19). These data could suggest that ML resistance in this parasite is not mediated through a reduced susceptibility of L 3 to the paralytic effects of ML drugs, and therefore motility-based assays are likely not appropriate for measuring the effects of MLs against D. immitis in this target stage. Published by Elsevier B.V.

Genetic profiles of ten Dirofilaria immitis isolates susceptible or resistant to macrocyclic lactone heartworm preventives

Directory of Open Access Journals (Sweden)

Catherine Bourguinat

2017-11-01

Full Text Available Abstract Background For dogs and cats, chemoprophylaxis with macrocyclic lactone (ML preventives for heartworm disease is widely used in the United States and other countries. Since 2005, cases of loss of efficacy (LOE of heartworm preventives have been reported in the U.S. More recently, ML-resistant D. immitis isolates were confirmed. Previous work identified 42 genetic markers that could predict ML response in individual samples. For field surveillance, it would be more appropriate to work on microfilarial pools from individual dogs with a smaller subset of genetic markers. Methods MiSeq technology was used to identify allele frequencies with the 42 genetic markers previously reported. Microfilaria from ten well-characterized new isolates called ZoeKY, ZoeMI, ZoeGCFL, ZoeAL, ZoeMP3, ZoeMO, ZoeAMAL, ZoeLA, ZoeJYD-34, and Metairie were extracted from fresh blood from dogs. DNA were extracted and sequenced with MiSeq technology. Allele frequencies were calculated and compared with the previously reported susceptible, LOE, and resistant D. immitis populations. Results The allele frequencies identified in the current resistant and susceptible isolates were in accordance with the allele frequencies previously reported in related phenotypes. The ZoeMO population, a subset of the ZoeJYD-34 population, showed a genetic profile that was consistent with some reversion towards susceptibility compared with the parental ZoeJYD-34 population. The Random Forest algorithm was used to create a predictive model using different SNPs. The model with a combination of three SNPs (NODE_42411_RC, NODE_21554_RC, and NODE_45689 appears to be suitable for future monitoring. Conclusions MiSeq technology provided a suitable methodology to work with the microfilarial samples. The list of SNPs that showed good predictability for ML resistance was narrowed. Additional phenotypically well characterized D. immitis isolates are required to finalize the best set of SNPs to be

Selective Extraction of Perrhenate and Pertechnetate by New Macrocyclic Compounds

International Nuclear Information System (INIS)

Paviet-Hartmann, Patricia; Horkley, Jared; Wolfrom, Earle; Pak, Joshua

2008-01-01

The long half-life of technetium-99 and its ability to form an anionic species makes it a major concern when considering long-term disposal of high-level radioactive waste. Furthermore, as its most stable species in the environment, the pertechnetate ion, TcO 4 - is highly mobile and is considered as a long-term hazard in nuclear waste disposal. There is a need for the development of new extractant systems, such as systems based on crown ethers that may serve to selectively extract and separate this long lived radionuclide from different streams for potential industrial application. In this paper, we are reporting the design and synthesis of new macrocyclic compounds to selectively extract technetium and rhenium from complex mixtures. Preliminary tests performed for the selective extraction of pertechnetate and perrhenate are presented. (authors)

Effects of lactone, ketone, and phenolic compounds on methane production and metabolic intermediates during anaerobic digestion.

Science.gov (United States)

Wikandari, Rachma; Sari, Noor Kartika; A'yun, Qurrotul; Millati, Ria; Cahyanto, Muhammad Nur; Niklasson, Claes; Taherzadeh, Mohammad J

2015-02-01

Fruit waste is a potential feedstock for biogas production. However, the presence of fruit flavors that have antimicrobial activity is a challenge for biogas production. Lactones, ketones, and phenolic compounds are among the several groups of fruit flavors that are present in many fruits. This work aimed to investigate the effects of two lactones, i.e., γ-hexalactone and γ-decalactone; two ketones, i.e., furaneol and mesifurane; and two phenolic compounds, i.e., quercetin and epicatechin on anaerobic digestion with a focus on methane production, biogas composition, and metabolic intermediates. Anaerobic digestion was performed in a batch glass digester incubated at 55 °C for 30 days. The flavor compounds were added at concentrations of 0.05, 0.5, and 5 g/L. The results show that the addition of γ-decalactone, quercetin, and epicathechin in the range of 0.5-5 g/L reduced the methane production by 50 % (MIC50). Methane content was reduced by 90 % with the addition of 5 g/L of γ-decalactone, quercetin, and epicathechin. Accumulation of acetic acid, together with an increase in carbon dioxide production, was observed. On the contrary, γ-hexalactone, furaneol, and mesifurane increased the methane production by 83-132 % at a concentration of 5 g/L.

New Macrocyclic Diamide from Rauvolfia Yunnanensis Tsiang

Institute of Scientific and Technical Information of China (English)

GENG Chang-an; LIU Xi-kui

2008-01-01

A new macrocyclic diamide, 22-membered macrocyclic diamide, named cyciodicaprylamide(2), and five known compounds, bis(2-ethylhexyl) phthalate(1), ethyl 3,4,5-trimethoxybenzoate(3), ethyl 3,4,5-trimethoxycinnamate (4), (+)-syringaresinol(5), loliolide(6), were isolated from the roots of Rauvolfia yunnanensis Tsiang. Their structures were elucidated based on NMR, 2D NMR, and MS spectrum, respectively. They were obtained from it for the first time.

Does evaluation of in vitro microfilarial motility reflect the resistance status of Dirofilaria immitis isolates to macrocyclic lactones?

Directory of Open Access Journals (Sweden)

Mary J. Maclean

2017-11-01

Full Text Available Abstract Background Several reports have confirmed that macrocyclic lactone-resistant isolates of Dirofilaria immitis are circulating in the United States; however, the prevalence and potential impact of drug resistance is unknown. We wished to assess computer-aided measurements of motility as a method for rapidly assessing the resistance status of parasite isolates. Methods Blood containing microfilariae (MF from two clinical cases with a high suspicion of resistance was fed to mosquitoes and the resultant L3 injected into dogs that were then treated with six doses of Heartgard® Plus (ivermectin + pyrantel; Merial Limited at 30-day intervals. In both cases patent heartworm infections resulted despite the preventive treatment. Microfilariae isolated from these dogs and other isolates of known resistance status were exposed to varying concentrations of ivermectin in vitro and their motility assessed 24 h later using computer-processed high-definition video imaging. Results We produced two isolates, Yazoo-2013 and Metairie-2014, which established patent infections despite Heartgard® Plus treatments. Measurements of the motility of MF of these and other isolates (Missouri, MP3 and JYD-27 following exposure to varying concentrations of ivermectin did not distinguish between susceptible and resistant heartworm populations. There was some evidence that the method of MF isolation had an influence on the motility and drug susceptibility of the MF. Conclusions We confirmed that drug-resistant heartworms are circulating in the southern United States, but that motility measurements in the presence of ivermectin are not a reliable method for their detection. This implies that the drug does not kill the microfilariae via paralysis.

Electron transfer reactions of macrocyclic compounds of cobalt

Energy Technology Data Exchange (ETDEWEB)

Heckman, R.A.

1978-08-01

The kinetics and mechanisms of reduction of H/sub 2/O/sub 2/, Br/sub 2/, and I/sub 2/ by various macrocyclic tetraaza complexes of cobalt(II), including Vitamin B/sub 12r/, were studied. The synthetic macrocycles studied were all 14-membered rings which varied in the degree of unsaturation,substitution of methyl groups on the periphery of the ring, and substitution within the ring itself. Scavenging experiments demonstrated that the reductions of H/sub 2/O/sub 2/ produce free hydroxyl radicals only in the case of Co((14)ane)/sup 2 +/ but with none of the others. In the latter instances apparently H/sub 2/O/sub 2/ simultaneously oxidizes the metal center and the ligand. The reductions of Br/sub 2/ and I/sub 2/ produce an aquohalocobalt(III) product for all reductants (except B/sub 12r/ + Br/sub 2/, which was complicated by bromination of the corrin ring). The mechanism of halogen reduction was found to involve rate-limiting inner-sphere electron transfer from cobalt to halogen to produce a dihalide anion coordinated to the cobalt center. This intermediate subsequently decomposes in rapid reactions to halocobalt(III) and halogen atom species or reacts with another cobalt(II) center to give two molecules of halocobalt(III). The reductions of halomethylcobaloximes and related compounds and diamminecobaloxime by Cr/sup 2 +/ were also studied. The reaction was found to be biphasic in all cases with the reaction products being halomethane (for the halomethylcobaloximes), Co/sup 2 +/ (in less than 100 percent yield), a Cr(III)-dimethylglyoxime species, a small amount of free dmgH/sub 2/, and a highly-charged species containing both cobalt and chromium. The first-stage reaction occurs with a stoichiometry of 1:1 producing an intermediate with an absorption maximum at 460 nm for all starting reagents. The results were interpreted in terms of inner-sphere coordination of the cobaloxime to the Cr(II) and electron transfer through the oxime N-O bond.

Discovery of new lactones in sweet cream butter oil.

Science.gov (United States)

Sarrazin, Elise; Frerot, Eric; Bagnoud, Alain; Aeberhardt, Kasia; Rubin, Mark

2011-06-22

Sweet cream butter oil was analyzed to identify new volatile compounds that may contribute to its flavor, with an emphasis on lactones. The volatile part of butter oil was obtained by using short-path distillation. As some previously unknown lactones were detected in this first extract, it was fractionated further. The fatty acids were removed, and the extract was fractionated by flash chromatography. Three lactonic fractions possessing a creamy, buttery, and fatty character were investigated in depth by gas chromatography (GC) and mass spectrometry (MS) (EI and CI) and high-resolution GC-time-of-flight MS. Many lactones were identified by their mass fragmentation and by comparison with reference materials synthesized during this work. Six γ-lactones, five δ-lactones, and one ε-lactone were identified for the first time in butter oil, seven of them for the first time in a natural product. The possible contribution of these new lactones to the aroma of butter oil is briefly discussed.

SESQUITERPENE LACTONES OF LEAVES AND FRUITS OF LAURUS NOBILIS L.

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D. A. Konovalov

2014-01-01

Full Text Available Bay laurel (Laurus nobilis L. is common in the Mediterranean region, Europe and America. Widely cultivated in the countries of the Arabian Peninsula and North Africa. As the basic active substances in plants: essential oil components, sesquiterpene lactones, alkaloids, and phenolic compounds (flavonoids, phenolic acids and lignans are described.In the plant more than 30 sesquiterpene lactones are found. Structural types of these compounds include eudesmanolides, germacranolides, guaianolides.Sesquiterpene lactones isolated from the leaves and fruits of Laurus nobilis, possess antibacterial, antifungal, anti-diabetic, anti-inflammatory, hepatoprotective, neuroprotective and cytotoxic activity. They inhibit the absorption of alcohol increases the activity of hepatic glutathione-S-transferase. Most of these types of activity of sesquiterpene lactones from laurel due to the presence within their structure of α-methylene--butyrolactone part.Thus, sesquiterpene lactones-containing leaves and fruits Laurus nobilis could have been an important source of raw materials for the creation of new medicines

Selective Extraction of Perrhenate and Pertechnetate by New Macrocyclic Compounds

Energy Technology Data Exchange (ETDEWEB)

Paviet-Hartmann, Patricia; Horkley, Jared; Wolfrom, Earle [Idaho State University/Idaho National Laboratory, 1776 Science Center Drive, Idaho Falls, ID 83402 (United States); Pak, Joshua [Idaho State University, 921 S. 8th Avenue, Pocatello, ID 83209 (United States)

2008-07-01

The long half-life of technetium-99 and its ability to form an anionic species makes it a major concern when considering long-term disposal of high-level radioactive waste. Furthermore, as its most stable species in the environment, the pertechnetate ion, TcO{sub 4}{sup -} is highly mobile and is considered as a long-term hazard in nuclear waste disposal. There is a need for the development of new extractant systems, such as systems based on crown ethers that may serve to selectively extract and separate this long lived radionuclide from different streams for potential industrial application. In this paper, we are reporting the design and synthesis of new macrocyclic compounds to selectively extract technetium and rhenium from complex mixtures. Preliminary tests performed for the selective extraction of pertechnetate and perrhenate are presented. (authors)

Cytotoxic sesquiterpene lactones and other constituents of Centaurea omphalotricha

Energy Technology Data Exchange (ETDEWEB)

Kolli, El Hadj; Leon, Francisco; Benayache, Samir, E-mail: jfleon@ipna.csic.es, E-mail: sbenayache@yahoo.com [Laboratoire de Valorisation des Ressources Naturelles et Synthese de Substances Bioactives, Equipe Associee a l' A.N.D.R.S., Universite Mentouri, Constantine (Algeria); Benayache, Fadila [Laboratoire de Phytochimie et Analyses Physico-Chimiques et Biologiques, Universite Mentouri, Constantine (Algeria); Estevez, Sara; Quintana, Jose; Estevez, Francisco [Departamento de Bioquimica, Unidad Asociada al CSIC, Facultad de Ciencias de la Salud, Universidad de Las Palmas de Gran Canaria (Spain); Instituto Canario de Investigacion del Cancer, Las Palmas de Gran Canaria, Gran Canaria (Spain); Brouard, Ignacio; Bermejo, Jaime [Instituto de Productos Naturales y Agrobiologia, CSIC, La Laguna, Tenerife (Spain)

2012-05-15

Phytochemical research of the aerial parts of Centaurea omphalotricha led to the isolation of three new sesquiterpene lactones, 4'-acetyl cynaropicrin, 4'-acetyl cebellin F and 15-acetyl dehydromelitensin, together with twelve known compounds, seven sesquiterpene lactones, two isoprenoids and three flavonoids. The structures of the new compounds were elucidated by means of extensive 1D and 2D NMR, and MS, and by comparison with reported data in the literature. The effect of sesquiterpene lactones on the viability of the human tumor cell lines HL-60 and U937 was also investigated and 3-acetyl cynaropicrin, and 4'-acetyl cynaropicrin were found to be the most cytotoxic compounds against human leukemia cells with an IC{sub 50} values of 2.0 =- 0.9 and 5.1 +- 0.4 {mu}mol L{sup -1}, respectively. (author)

Comprehensive computational design of ordered peptide macrocycles

Energy Technology Data Exchange (ETDEWEB)

Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram K.; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fatima; Rettie, Stephan A.; Kim, David E.; Silva, Daniel A.; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

2017-12-14

Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible through library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.

Fragrance material review on hexadecanolide.

Science.gov (United States)

McGinty, D; Letizia, C S; Api, A M

2011-12-01

A toxicologic and dermatologic review of hexadecanolide when used as a fragrance ingredient is presented. Hexadecanolide is a member of the fragrance structural group macrocyclic lactone and lactide derivatives. The fragrance ingredient described herein is one of 12 structurally diverse C14, C15, and C16 compounds that include (7) saturated mono-and (2) saturated di-ester lactones and (3) unsaturated lactones. For the latter, the double bond is not adjacent to (in conjugation with) the ester group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for hexadecanolide were evaluated, then summarized, and includes: physical properties; acute toxicity; skin irritation; mucous membrane (eye) irritation; skin sensitization; phototoxicity; and genotoxicity data. A safety assessment of the macrocyclic lactone and lactide derivatives will be published simultaneously with this document. Please refer to Belsito et al. (2011) for an overall assessment of the safe use of this material and all macrocyclic lactone and lactide derivatives in fragrances. Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Hanifin, J.H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A Toxicologic and Dermatologic Assessment of Macrocylic Lactones and Lactide Derivatives When Used as Fragrance Ingredients. Copyright © 2011. Published by Elsevier Ltd.

Structural and Sensory Characterization of Novel Sesquiterpene Lactones from Iceberg Lettuce.

Science.gov (United States)

Mai, Franziska; Glomb, Marcus A

2016-01-13

Lactuca sativa var. capitate (iceberg lettuce) is a delicious vegetable and popular for its mild taste. Nevertheless, iceberg lettuce is a source of bitter substances, such as the sesquiterpene lactones. Chemical investigations on the n-butanol extract led to the isolation of three novel sesquiterpene lactones. All compounds were isolated by multilayer countercurrent chromatography followed by preparative high-performance liquid chromatography. The structures were verified by means of spectroscopic methods, including NMR and mass spectrometry techniques. For the first time 11ß,13-dihydrolactucin-8-O-sulfate (jaquinelin-8-O-sulfate) was structurally elucidated and identified in plants. In addition, the sesquiterpene lactones cichorioside B and 8-deacetylmatricarin-8-O-sulfate were identified as novel ingredients of iceberg lettuce. Further flowering plants in the daisy family Asteraceae were examined for the above three compounds. At least one of the compounds was identified in nine plants. The comparison between the lettuce butt end and the leaves of five types of the Cichorieae tribe showed an accumulation of the compounds in the butt end. Further experiments addressed the impact of sesquiterpene lactones on color formation and bitter taste.

New sesquiterpene lactones from sunflower root exudate as germination stimulants for Orobanche cumana.

Science.gov (United States)

Raupp, Frank M; Spring, Otmar

2013-11-06

Orobanche cumana is a serious threat for cultivation of sunflower in Europe and Asia. Germination of the parasite is induced by metabolites released from the host root system. The first germination stimulant from sunflower root exudate was recently identified as dehydrocostus lactone, a sesquiterpene lactone. Bioassay-guided fractionation of root exudates now showed the release of additional sesquiterpene lactones. Besides dehydrocostus lactone, costunolide, tomentosin, and 8-epixanthatin were purified and identified spectroscopically. All four compounds induced germination of O. cumana at nano- to micromolar concentrations. Costunolide and dehydrocostus lactone concentrations above 1 μM reduced the activity, and application of 100 μM inhibited germination irreversibly. Seeds of Phelipanche ramosa could not be induced with costunolide. O. cumana seeds also germinated with GR24, a synthetic strigolactone. No bioactive fraction of sunflower contained compounds of this type. This supports previous findings that sesquiterpene lactones instead of strigolactones trigger the sunflower/O. cumana interaction.

Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis

Directory of Open Access Journals (Sweden)

Bianca Ivanescu

2015-01-01

Full Text Available Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation.

Sesquiterpene lactone stereochemistry influences herbivore resistance and plant fitness in the field.

Science.gov (United States)

Ahern, Jeffrey R; Whitney, Kenneth D

2014-03-01

Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant-herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field. Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness. The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide. To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing

Diterpene lactones with labdane, halimane and clerodane frameworks.

Science.gov (United States)

Silva, Lúcia; Gomes, Arlindo C; Rodilla, Jesus M L

2011-04-01

The labdane, halimane and clerodane type diterpenoids are compounds that have been isolated in plants of several families. These molecules and their derivatives with a lactone group on the side chain or on the decaline system, have a great interest because of their biological properties as insect antifeedant, antiviral, cytotoxic and trypanocidal. The scope of this review is lactones diterpenoids with labdane, halimane and clerodane frameworks.

Structural basis of nonribosomal peptide macrocyclization in fungi.

Science.gov (United States)

Zhang, Jinru; Liu, Nicholas; Cacho, Ralph A; Gong, Zhou; Liu, Zhu; Qin, Wenming; Tang, Chun; Tang, Yi; Zhou, Jiahai

2016-12-01

Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (C T ) domain and the holo thiolation (T)-C T complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

Biosynthesis of sesquiterpene lactones in pyrethrum (Tanacetum cinerariifolium)

DEFF Research Database (Denmark)

Ramirez, Aldana M; Saillard, Nils; Yang, Ting

2013-01-01

The daisy-like flowers of pyrethrum (Tanacetum cinerariifolium) are used to extract pyrethrins, a botanical insecticide with a long history of safe and effective use. Pyrethrum flowers also contain other potential defense compounds, particularly sesquiterpene lactones (STLs), which represent...... these reported bioactivities and industrial significance, the biosynthetic origin of pyrethrum sesquiterpene lactones remains unknown. In the present study, we show that germacratrien-12-oic acid is most likely the central precursor for all sesquiterpene lactones present in pyrethrum. The formation...... of the lactone ring depends on the regio- (C6 or C8) and stereo-selective (α or β) hydroxylation of germacratrien-12-oic acid. Candidate genes implicated in three committed steps leading from farnesyl diphosphate to STL and other oxygenated derivatives of germacratrien-12-oic acid were retrieved from a pyrethrum...

Structural basis for precursor protein-directed ribosomal peptide macrocyclization

Science.gov (United States)

Li, Kunhua; Condurso, Heather L.; Li, Gengnan; Ding, Yousong; Bruner, Steven D.

2016-01-01

Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides whose members target proteases with potent reversible inhibition. The product structure is constructed by three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here, we describe the detailed structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases, MdnC and MdnB, interact with a conserved α-helix of the precursor peptide using a novel precursor peptide recognition mechanism. The results provide insight into the unique protein/protein interactions key to the chemistry, suggest an origin of the natural combinatorial synthesis of microviridin peptides and provide a framework for future engineering efforts to generate designed compounds. PMID:27669417

Structural basis for precursor protein-directed ribosomal peptide macrocyclization.

Science.gov (United States)

Li, Kunhua; Condurso, Heather L; Li, Gengnan; Ding, Yousong; Bruner, Steven D

2016-11-01

Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein-protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.

Confirmation of the definitive structure of Fleishmann's lactone by NMR

International Nuclear Information System (INIS)

Figueroa Villar, Jose Daniel

1993-01-01

The reaction between 4-hydroxy-6-methyl-pyrone and ethyl-acetic-acetate produces a compound known since the beginning of the century, named Fleishman lactone in honor to its discover. The structure of this compound has been the aim of several researches due to its similarity with several poly-pyrones which are important in synthesis of important products. This work presents the accurate determination of the structure of the Fleishman lactone. The methodology is presented as well as confirmation tests

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds.

Science.gov (United States)

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R

2015-04-21

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

A strategy for the diversity-oriented synthesis of macrocyclic scaffolds using multidimensional coupling

DEFF Research Database (Denmark)

Beckmann, Henning S G; Nie, Feilin; Hagerman, Caroline E

2013-01-01

the coupling reaction. We applied this step-efficient approach in a DOS of a library that consisted of 73 macrocyclic compounds based around 59 discrete scaffolds. The macrocycles prepared cover a broad range of different molecular shapes, as illustrated by principal moment-of-inertia analysis...

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

Science.gov (United States)

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

2016-10-01

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

Sesquiterpene lactones in two endemic Anthemis species

International Nuclear Information System (INIS)

Staneva, J.; Todorova, M.; Evstatieva, L.; Dimitrov, D.

2006-01-01

The aerial parts of Anthemis stribrnyi subsp.tracica and A. macedonica afforded four and nine sesquiterpene lactones, respectively. Their structures were elucidated by spectral methods. Acetylisospiciformin is a new natural compound. (authors)

Tools for Chemical Biology: New Macrocyclic Compounds from Diversity-Oriented Synthesis and Toward Materials from Silver(I) Acetylides

DEFF Research Database (Denmark)

Madsen, Charlotte Marie

Part I The formation of a library of diverse macrocyclic compounds with different functionalities and ring sizes in a few steps from two easily accessible α,ω-diol building blocks is presented. The building blocks are combined by esteriffcations in four different ways leading to the formation of ...... of uoro-iodoadamantanes. However, overall the results provide a good starting point for the synthesis of new triptycene and adamantane-containing molecules that can interact with carbon nanotubes....

Ketopantoyl lactone reductase is a conjugated polyketone reductase.

Science.gov (United States)

Hata, H; Shimizu, S; Hattori, S; Yamada, H

1989-03-01

Ketopantoyl lactone reductase (EC 1.1.1.168) of Saccharomyces cerevisiae was found to catalyze the reduction of a variety of natural and unnatural conjugated polyketone compounds and quinones, such as isatin, ninhydrin, camphorquinone and beta-naphthoquinone in the presence of NADPH. 5-Bromoisatin is the best substrate for the enzyme (Km = 3.1 mM; Vmax = 650 mumol/min/mg). The enzyme is inhibited by quercetin, and several polyketones. These results suggest that ketopantoyl lactone reductase is a carbonyl reductase which specifically catalyzes the reduction of conjugated polyketones.

Characterization and crystal structures of new Schiff base macrocyclic compounds

Czech Academy of Sciences Publication Activity Database

Khalaji, A.D.; Ghoran, S.H.; Pojarová, Michaela; Dušek, Michal

2015-01-01

Roč. 56, č. 7 (2015), s. 1410-1414 ISSN 0022-4766 R&D Projects: GA ČR(CZ) GA14-03276S Institutional support: RVO:68378271 Keywords : synthesis * macrocyclic Schiff base * single crystal structure analysis * spectroscopy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.536, year: 2015

Synthetic approaches to aromatic belts: building up strain in macrocyclic polyarenes.

Science.gov (United States)

Eisenberg, David; Shenhar, Roy; Rabinovitz, Mordecai

2010-08-01

This tutorial review discusses synthetic strategies towards aromatic belts, defined here as double-stranded conjugated macrocycles, such as [n]cyclacenes, [n]cyclophenacenes, Schlüter belt, and Vögtle belt. Their appeal stems, firstly, from the unique nature of their conjugation, having p orbitals oriented radially rather than perpendicular to the plane of the macrocycle. Secondly, as aromatic belts are model compounds of carbon nanotubes of different chiralities, a synthetic strategy towards the buildup of structural strain in these compounds could finally open a route towards rational chemical synthesis of carbon nanotubes. The elusiveness of these compounds has stimulated fascinating and ingenious synthetic strategies over the last decades. The various strategies are classified here by their approach to the buildup of structural strain, which is the main obstacle in the preparation of these curved polyarenes.

Macrocyclic 2,7-Anthrylene Oligomers.

Science.gov (United States)

Yamamoto, Yuta; Wakamatsu, Kan; Iwanaga, Tetsuo; Sato, Hiroyasu; Toyota, Shinji

2016-05-06

A macrocyclic compound consisting of six 2,7-anthrylene units was successfully synthesized by Ni-mediated coupling of the corresponding dibromo precursor as a novel π-conjugated compound. This compound was sufficiently stable and soluble in organic solvents due to the presence of mesityl groups. X-ray analysis showed that the molecule had a nonplanar and hexagonal wheel-shaped framework of approximately S6 symmetry. The dynamic process between two S6 structures was observed by using the dynamic NMR technique, the barrier being 58 kJ mol(-1) . The spectroscopic properties of the hexamer were compared with those of analogous linear oligomers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Andrographolide: A Novel Antimalarial Diterpene Lactone Compound from Andrographis paniculata and Its Interaction with Curcumin and Artesunate

Directory of Open Access Journals (Sweden)

Kirti Mishra

2011-01-01

Full Text Available Andrographolide (AND, the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plant Andrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium falciparum in vitro and Plasmodium berghei ANKA in vivo. IC50s for artesunate (AS, andrographolide (AND, and curcumin (CUR were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND was found synergistic with curcumin (CUR and addictively interactive with artesunate (AS. In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%, compared to the control (81%, but also by extending the life span by 2-3 folds. Being nontoxic to the in vivo system this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

MacroEvoLution: A New Method for the Rapid Generation of Novel Scaffold-Diverse Macrocyclic Libraries.

Science.gov (United States)

Saupe, Jörn; Kunz, Oliver; Haustedt, Lars Ole; Jakupovic, Sven; Mang, Christian

2017-09-04

Macrocycles are a structural class bearing great promise for future challenges in medicinal chemistry. Nevertheless, there are few flexible approaches for the rapid generation of structurally diverse macrocyclic compound collections. Here, an efficient method for the generation of novel macrocyclic peptide-based scaffolds is reported. The process, named here as "MacroEvoLution", is based on a cyclization screening approach that gives reliable access to novel macrocyclic architectures. Classification of building blocks into specific pools ensures that scaffolds with orthogonally addressable functionalities are generated, which can easily be used for the generation of structurally diverse compound libraries. The method grants rapid access to novel scaffolds with scalable synthesis (multi gram scale) and the introduction of further diversity at a late stage. Despite being developed for peptidic systems, the approach can easily be extended for the synthesis of systems with a decreased peptidic character. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Biosynthesis of Sesquiterpene Lactones in Pyrethrum (Tanacetum cinerariifolium)

NARCIS (Netherlands)

Ramirez, A.M.; Saillard, N.; Yang, T.; Franssen, M.C.R.; Bouwmeester, H.J.; Jongsma, M.A.

2013-01-01

The daisy-like flowers of pyrethrum (Tanacetum cinerariifolium) are used to extract pyrethrins, a botanical insecticide with a long history of safe and effective use. Pyrethrum flowers also contain other potential defense compounds, particularly sesquiterpene lactones (STLs), which represent

Multicomponent Syntheses of Macrocycles

Science.gov (United States)

Masson, Géraldine; Neuville, Luc; Bughin, Carine; Fayol, Aude; Zhu, Jieping

How to access efficiently the macrocyclic structure remained to be a challenging synthetic topic. Although many elegant approaches/reactions have been developed, construction of diverse collection of macrocycles is still elusive. This chapter summarized the recently emerged research area dealing with multicomponent synthesis of macrocycles, with particular emphasis on the approach named "multiple multicomponent reaction using two bifunctional building blocks".

Sesquiterpene Lactones from Gynoxys verrucosa and their Anti-MRSA Activity

Science.gov (United States)

Ordóñez, Paola E.; Quave, Cassandra L.; Reynolds, William F.; Varughese, Kottayil I.; Berry, Brian; Breen, Philip J.; Malagón, Omar; Smeltzer, Mark S.; Compadre, Cesar M.

2011-01-01

Ethnopharmacological relevance Because of its virulence and antibiotic resistance, Staphylococcus aureus is a more formidable pathogen now than at any time since the pre-antibiotic era. In an effort to identify and develop novel antimicrobial agents with activity against this pathogen, we have examined Gynoxys verrucosa Wedd (Asteraceae), an herb used in traditional medicine in southern Ecuador for the treatment and healing of wounds. Materials and Methods The sesquiterpene lactones leucodine (1) and dehydroleucodine (2) were extracted and purified from the aerial parts of G. verrucosa, and their structure was elucidated by spectroscopic methods and single-crystal X-ray analysis. The in vitro anti-microbial activity of G. verrucosa extracts and its purified constituents was determined against six clinical isolates including S. aureus and Staphylococcus epidermidis strains with different drug-resistance profiles, using the microtiter broth method. Results Compound 1 has very low activity, while compound 2 has moderate activity with MIC50s between 49 and195 μg/mL. The extract of G. verrucosa has weak activity with MIC50s between 908 and 3290 μg/mL. Conclusions We are reporting the full assignment of the 1H-NMR and 13C-NMR of both compounds, and the crystal structure of compound 2, for the first time. Moreover, the fact that compound 2 has antimicrobial activity and compound 1 does not, demonstrates that the exocyclic conjugated methylene in the lactone ring is essential for the antimicrobial activity of these sesquiterpene lactones. However, the weak activity observed for the plants extracts, does not explain the use of G. verrucosa in traditional medicine for the treatment of wounds and skin infections. PMID:21782013

Through-Space Paramagnetic NMR Effects in Host-Guest Complexes: Potential Ruthenium(III) Metallodrugs with Macrocyclic Carriers.

Science.gov (United States)

Chyba, Jan; Novák, Martin; Munzarová, Petra; Novotný, Jan; Marek, Radek

2018-04-05

The potential of paramagnetic ruthenium(III) compounds for use as anticancer metallodrugs has been investigated extensively during the past several decades. However, the means by which these ruthenium compounds are transported and distributed in living bodies remain relatively unexplored. In this work, we prepared several novel ruthenium(III) compounds with the general structure Na + [ trans-Ru III Cl 4 (DMSO)(L)] - (DMSO = dimethyl sulfoxide), where L stands for pyridine or imidazole linked with adamantane, a hydrophobic chemophore. The supramolecular interactions of these compounds with macrocyclic carriers of the cyclodextrin (CD) and cucurbit[ n]uril (CB) families were investigated by NMR spectroscopy, X-ray diffraction analysis, isothermal titration calorimetry, and relativistic DFT methods. The long-range hyperfine NMR effects of the paramagnetic guest on the host macrocycle are related to the distance between them and their relative orientation in the host-guest complex. The CD and CB macrocyclic carriers being studied in this account can be attached to a vector that attracts the drug-carrier system to a specific biological target and our investigation thus introduces a new possibility in the field of targeted delivery of anticancer metallodrugs based on ruthenium(III) compounds.

Simultaneous Determination of Flavonols and Terpene Lactones in ...

African Journals Online (AJOL)

Lactones in Beagle Dog Plasma by Ultra-Performance ... School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China ... Purpose: To evaluate the pharmacokinetics of the major compounds in Ginkgo leaf dosage ... pharmacological effect. .... conversion factor was calculated as in Eq 1.

Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates

International Nuclear Information System (INIS)

Dadachova, E.; Chappell, L.L.; Brechbiel, M.W.

1999-01-01

A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2-[4-nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N'''' -pentaacetic acid), and the large 18-membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N'',N''',N''''-hexaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 μM, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (L/P ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle (2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N'',N'''-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands

Triazole-containing N-acyl homoserine lactones targeting the quorum sensing system in Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Hansen, Mette Reimert; Jakobsen, Tim H.; Bang, Claus Gunnar

2015-01-01

the pathogenesis and antibiotic tolerance of a bacterial biofilm. To identify the structural elements important for antagonistic or agonistic activity against the Pseudomonas aeruginosa LasR protein, we report the synthesis and screening of new triazole-containing mimics of natural N-acyl homoserine lactones....... A series of azide- and alkyne-containing homoserine lactone building blocks was used to prepare an expanded set of 123 homoserine lactone analogues through a combination of solution- and solid-phase synthesis methods. The resulting compounds were subjected to cell-based quorum sensing screening assays...

preparation of bicyclic lactones using lewis acids catalyzed ene

African Journals Online (AJOL)

Administrator

The synthesis of the cis-fused bicyclic lactones relies extensively on the Lewis acid ... having an allylic hydrogen (an"ene") and a compound containing an electron .... observed that the lithium enolate obtained from 3-methyl-2(5H)- furanone ...

Photolysis of Heterocyclic Lactones in Cryogenic Inert Matrices

International Nuclear Information System (INIS)

Kus, N.

2008-01-01

Heterocyclic lactones receive important uses in organic synthesis and are important biologically active compounds. Their weak toxicity and easy synthesis have made these compounds the subject of great interest and extensive investigation. Since long ago, lactones have been shown to possess an interesting photochemistry. Some representative six- and five-membered conjugated lactones [α-pyrone and some of its derivatives, including coumarin and 3-acetamido coumarin, 2(5H)-furanone] were recently investigated by infrared spectroscopy using the matrix isolation technique and quantum chemical calculations in our laboratories. Two main competitive photochemical reaction pathways could be identified: (i) ring-opening, leading to formation of the isomeric aldehyde-ketene, and (ii) ring-contraction leading to the corresponding Dewar isomers. For α-pyrone and 2(5H)-furanone, the ring-opening process dominates over the ring-contraction reaction, the same occurring for derivatives of these compounds bearing a voluminous substituent at position 3. In 2(5H)-furanone, the ring-opening reaction requires the simultaneous occurrence of a [1,2]-hydrogen atom migration, which was found to occur upon excitation at λ> 235 nm. Under the identical UV-irradiation (λ> 235 nm) of the six-membered analogues, the ring-opening reaction was more efficient in α-pyrone than in coumarin, and factors explaining this observation will be discussed. In turn, the Dewar forms of the studied compounds, resulting from the ring-contraction photoreaction, were found to undergo subsequent photo-elimination of CO 2 , with formation of the corresponding cycloalkenes. In the matrices, CO 2 and the simultaneously formed cycloalkenes were predicted by calculations to exist as associates, in which the CO 2 molecule is preferentially placed over the cycloalkene ring in a stacked-type geometry. For coumarin, a third photoreaction channel was observed, leading to formation of benzofurane and CO. This additional

Use of macrocycle- or hemisepulcrand-type poly(oxygen) compounds in nuclear hydrometallurgy. Study of the diluent effect: supra-molecular approach

International Nuclear Information System (INIS)

Bethmont, Valerie

1997-01-01

Liquid/liquid extraction has been used for many years to obtain high purity nuclear fuels (uranium salts and plutonium salts), notably with the Purex process which allows 99 per cent of uranium and plutonium contained by spent nuclear fuels to be recovered. This research thesis deals with the search for new and steadier extracting agents, and focuses on macro-cycle or hemisepulcrand type poly(oxygenated) compounds which have excellent properties in nuclear hydrometallurgy. The author thus first discusses the synthesis of oxygenated tripodands (bibliographical study and development of a catalytic method to synthesise ethers). Then, she reports the use of poly(oxygenated) compounds in liquid/liquid extraction, and the experimental study of the effect of the diluting agent by using a supramolecular approach [fr

Kinetic investigation of uranyl-uranophile complexation. 1. Macrocyclic kinetic effect and macrocyclic protection effect

International Nuclear Information System (INIS)

Tabushi, I.; Yoshizawa, A.

1986-01-01

Equilibria and rates of ligand-exchange reactions between uranyl tricarbonate and dithiocarbamates and between uranyl tris-(dithiocarbamates) and carbonate were studied under a variety of conditions. The dithiocarbamates used were acyclic diethyl-dithiocarbamate and macrocyclic tris(dithiocarbamate). The acyclic ligand showed a triphasic (successive three-step) equilibrium with three different equilibrium constants while the macrocyclic ligand showed a clear monophasic (one-step) equilibrium with a much larger stability constant for the dithiocarbamate-uranyl complex. The macrocyclic ligand showed the S/sub N/2-type ligand-exchange rate in the forward as well as reverse process, while the first step of the acyclic ligand-exchange reaction proceeded via the S/sub N/1-type mechanism. This kinetic macrocyclic effect on molecularity is interpreted as the result of a unique topological requirement of uranyl complexation. The macrocyclic ligand also exhibited a clear protection effect, leading to the large stability constant. 19 references, 10 figures, 2 tables

Solid‐Phase Synthesis and Biological Evaluation of N‐Dipeptido L‐Homoserine Lactones as Quorum Sensing Activators

DEFF Research Database (Denmark)

Hansen, Mette Reimert; Le Quement, Sebastian Thordal; Jakobsen, Tim Holm

2014-01-01

‐homoserine lactones. With the goal of identifying non‐native compounds capable of modulating bacterial QS, a virtual library of N‐dipeptido L‐homoserine lactones was screened in silico with two different crystal structures of LasR. The 30 most promising hits were synthesized on HMBA‐functionalized PEGA resin...

A macrocyclic ellagitannin trimer, oenotherin T(1), from Oenothera species.

Science.gov (United States)

Taniguchi, Shoko; Imayoshi, Yoko; Yabu-uchi, Ryoko; Ito, Hideyuki; Hatano, Tsutomu; Yoshida, Takashi

2002-01-01

Oenotherin T(1) was isolated from leaves of Oenothera tetraptera as a major ellagitannin. Its structure, that of a macrocyclic trimer with a new acyl group, an isodehydrovaloneoyl group, was established. This compound was also produced by callus tissues induced from O. laciniata leaves.

Lactones with Methylcyclohexane Systems Obtained by Chemical and Microbiological Methods and Their Antimicrobial Activity

Directory of Open Access Journals (Sweden)

Małgorzata Grabarczyk

2015-02-01

Full Text Available Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones, each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl acetic acid or (6-methylcyclohex-2-en-1-yl acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea were tested on their ability to convert these lactones into other products. Some of the tested fungal strains transformed chloro-, bromo- and iodolactone with a methyl group at C-5 into 2-hydroxy-5-methyl-9-oxabicyclo[4.3.0]nonan-8-one during hydrolytic dehalogenation. When the same lactones had the methyl group at C-3, no structural modifications of halolactones were observed. In most cases, the optical purity of the product was low or medium, with the highest rate for chlorolactone (45.4% and iodolactone (45.2% and 47.6%. All of the obtained compounds were tested with reference to their smell. Seven halolactones and the hydroxylactone obtained via biotransformation of halolactones with 5-methylcyclohexane ring were examined for their antimicrobial activity. These compounds were capable of inhibiting growth of some bacteria, yeasts and fungi.

Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

DEFF Research Database (Denmark)

Olsen, Christian Adam; Montero, Ana; Leman, Luke J.

2012-01-01

We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC...

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism.

Science.gov (United States)

Vollmeyer, Joscha; Eberhagen, Friederike; Höger, Sigurd; Jester, Stefan-S

2014-01-01

Three shape-persistent naphthylene-phenylene-acetylene macrocycles of identical backbone structures and extraannular substitution patterns but different (empty, apolar, polar) nanopore fillings are self-assembled at the solid/liquid interface of highly oriented pyrolytic graphite and 1,2,4-trichlorobenzene. Submolecularly resolved images of the resulting two-dimensional (2D) crystalline monolayer patterns are obtained by in situ scanning tunneling microscopy. A concentration-dependent conformational polymorphism is found, and open and more dense packing motifs are observed. For all three compounds alike lattice parameters are found, therefore the intermolecular macrocycle distances are mainly determined by their size and symmetry. This is an excellent example that the graphite acts as a template for the macrocycle organization independent from their specific interior.

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism

Directory of Open Access Journals (Sweden)

Joscha Vollmeyer

2014-11-01

Full Text Available Three shape-persistent naphthylene–phenylene–acetylene macrocycles of identical backbone structures and extraannular substitution patterns but different (empty, apolar, polar nanopore fillings are self-assembled at the solid/liquid interface of highly oriented pyrolytic graphite and 1,2,4-trichlorobenzene. Submolecularly resolved images of the resulting two-dimensional (2D crystalline monolayer patterns are obtained by in situ scanning tunneling microscopy. A concentration-dependent conformational polymorphism is found, and open and more dense packing motifs are observed. For all three compounds alike lattice parameters are found, therefore the intermolecular macrocycle distances are mainly determined by their size and symmetry. This is an excellent example that the graphite acts as a template for the macrocycle organization independent from their specific interior.

Relationship between Menthiafolic Acid and Wine Lactone in Wine.

Science.gov (United States)

Giaccio, Joanne; Curtin, Chris D; Sefton, Mark A; Taylor, Dennis K

2015-09-23

Menthiafolic acid (6-hydroxy-2,6-dimethylocta-2,7-dienoic acid, 2a) was quantified by GC-MS in 28 white wines, 4 Shiraz wines, and for the first time in 6 white grape juice samples. Menthiafolic acid was detected in all but one of the wine samples at concentrations ranging from 26 to 342 μg/L and in the juice samples from 16 to 236 μg/L. Various model fermentation experiments showed that some menthiafolic acid in wine could be generated from the grape-derived menthiafolic acid glucose ester (2b) during alcoholic and malolactic fermentation. Samples containing high concentrations of menthiafolic acid were also analyzed by enantioselective GC-MS and were shown to contain this compound in predominantly the (S)-configuration. Enantioselective analysis of wine lactone (1) in one of these samples, a four-year-old Chardonnay wine showed, for the first time, the presence of the 3R,3aR,7aS isomer of wine lactone (1b), which is the enantiomer of the form previously reported as the sole isomer present in young wine samples. The weakly odorous 3R,3aR,7aS 1b form comprised 69% of the total wine lactone in the sample. On the basis of the enantioselectivity of the hydrolytic conversion of menthiafolic acid to wine lactone at pH 3.0 determined previously and the relative proportions of (R)- and (S)-menthiafolic acid in the Chardonnay wine, the predicted ratio of wine lactone enantiomers that would be formed from hydrolysis at ambient temperature of the menthiafolic acid present in this wine was close to the ratio measured, which was consistent with menthiafolic acid being the major or sole precursor to wine lactone in this sample.

Analysis, potency and occurrence of (Z)-6-dodeceno-γ-lactone in white wine.

Science.gov (United States)

Siebert, Tracey E; Barker, Alice; Barter, Sheridan R; de Barros Lopes, Miguel A; Herderich, Markus J; Francis, I Leigh

2018-08-01

(Z)-6-Dodeceno-γ-lactone is a potent aroma compound that has been little studied and its prevalence in wines is unknown. An efficient stable isotope dilution assay was developed using a simple, direct immersion solid-phase microextraction and gas chromatography-tandem mass spectrometry method suitable for routine use with a low ng/L limit of quantitation. Using this method, 99 out of 104 young white wines analysed were found to contain detectable (Z)-6-dodeceno-γ-lactone. The highest concentrations were found in Riesling and Viognier wines. (Z)-6-Dodeceno-γ-lactone was found to have an aroma detection threshold of 700 ng/L in a neutral white wine. This study established that (Z)-6-dodeceno-γ-lactone is widely present in Australia's most popular white wine varieties, but generally at concentrations below its aroma detection threshold. Copyright © 2018 Elsevier Ltd. All rights reserved.

Interkingdom signaling: The role of homoserine lactones in early responses and resistance in barley (Hordeum vulgare L.)

OpenAIRE

Rankl, Simone

2017-01-01

N-Acyl-D/L-homoserine lactones (AHLs) are produced as microbial signaling compounds during bacterial intra- and inter-specific communication in the rhizosphere. Thus, plants are naturally exposed to these compounds and respond with tissue-specific reactions. In the present study the impact of AHLs on the monocot barley (Hordeum vulgare L.) was investigated. The treatment with C8- and C12- homoserine lactones (HSL) resulted in root and shoot biomass gain as well as in the formation of lat...

Synthesis and study of rare earth complexes with ortho-hydroxyphenyliminodiacetic acid containing lactone ring

International Nuclear Information System (INIS)

Martynenko, L.I.; Mitrofanova, N.D.; Muratova, N.M.; Kurbatova, S.V.

1978-01-01

Solid complex compounds of o-oxyphenyliminodiacetic acid with rare earth elements of the composition of LnA 2 Clx6H 2 O and LnA 3 x5H 2 O (where Ln=La, Pr, Nd, Eu, Dy, Er, and Y) not described earlier, have been synthesized. The thermographic analysis of the compounds has been performed. It is shown by infrared spectroscopy that a lactone ring is retained in the dicomplex structure. The presence of the absorption bands of non-ionized COOH-groups in the infrared spectra of tricomplexonates of heavy r.e.e. points to opening of the lactone ring in the ligand part

Antiprotozoal Activity of α,β-Unsaturated δ-Lactones: Promising ...

African Journals Online (AJOL)

The parasite resistance and side effects of drugs used to treat protozoal diseases have led to the search for new therapies, both natural and synthetic. Studies have shown that various α,β-unsaturated δ-lactones displayed high antiprotozoal activity and thus are promising compounds for new drug discovery and ...

Stability complexes of lanthanide ions with some macrocyclic polyethers

International Nuclear Information System (INIS)

Poluehktov, N.S.; Malinka, E.V.; Meshkova, S.B.; Bel'tyukova, S.V.; Danilkovich, M.M.

1984-01-01

Stability of lanthanide complexes with macrocyclic polyethers has been studied versus the number of f-electrons, spin- and orbital angular momenta of the Lu 3+ ion ground states. The following compounds were used as macrocyclic complexones: 12-crown-4 (12C4), tert-bulylbenzo-15-crown-5(BB15C5), 18-crown-6 (18C6), ditert-butylbenzo-18-crown-6(DBB18C6), dibenzo-30-crown-10 (DB30C10), cryptand [2, 2, 1] (Cr[2, 2, 1]). It is shoWn that the stability constants of the studied lanthanide complexes can be described rather satisfactorily by an expression suggested earlier that relates their values with the number of 4f-electrons and the S and L quantum numbers of the ground states of the lantharide ions

Radiolytic and photochemical reduction of carbon dioxide in solution catalyzed by transition metal complexes with some selected macrocycles

International Nuclear Information System (INIS)

Grodkowski, J.

2004-01-01

The main goal of the work presented in this report is an explanation of the mechanism of carbon dioxide (CO 2 ) reduction catalyzed by transition metal complexes with some selected macrocycles. The catalytic function of two electron exchange centers in the reduction of CO 2 , an inner metal and a macrocycle ring, was defined. Catalytic effects of rhodium, iron and cobalt porphyrins, cobalt and iron phthalocyanines and corroles as well as cobalt corrins have been investigated. CO 2 reduction by iron ions without presence of macrocycles and also in presence of copper compounds in aqueous solutions have been studied as well

Natural sesquiterpen lactones as acetylcholinesterase inhibitors

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HOMA HAJIMEHDIPOOR

2014-06-01

Full Text Available Background and the purpose of the study: The amount of elder people who suffer from Alzheimer disease is continuously increasing every year. Cholinesterase inhibitors have shown to be effective in alleviating the symptoms of the disease, thus opening a field of research for these treatments. Herbal products, owning a reputation as effective agents in many biological studies are now drawing attention for inhibiting acetylcholinesterase, in other words, Alzheimer disease. In the present study, the ability of three sesquiterpene lactones from Inula oculus-christi and I. aucheriana to inhibit AChE has been evaluated through Ellman assay.Materials and Methods: Gaillardin and pulchellin C were obtained from I. oculus-christi and britannin from I. aucheriana by chromatographic methods. They were dissolved in methanol in concentration of 3 mg/mL and the AChEI activity of the compounds was determined by Ellman method using Acethylthiocholine iodide as the substrate and 5, 5′-dithiobis-2-nitrobenzoic acid as the reagent, in 96-well plates at 405 nm.Results: AChEI activity of the examined compounds was obtained as 67.0, 25.2 and 10.9% in concentration of 300 µg/L for gaillardin, britannin and pulchellin C, respectively.Conclusion: Among the three sesquiterpene lactones, gaillardin with 67% inhibition of AChE could be considered a good candidate for future Alzheimer studies.

Design and synthesis of macrocyclic peptidyl hydroxamates as peptide deformylase inhibitors.

Science.gov (United States)

Shen, Gang; Zhu, Jinge; Simpson, Anthony M; Pei, Dehua

2008-05-15

Macrocyclic peptidyl hydroxamates were designed, synthesized, and evaluated as peptide deformylase (PDF) inhibitors. The most potent compound exhibited tight, slow-binding inhibition of Escherichia coli PDF (K(I)(*)=4.4 nM) and had potent antibacterial activity against Gram-positive bacterium Bacillus subtilis (MIC=2-4 microg/mL).

Sesquiterpene lactones. XXXII. Guaianolides in species from the genus Chartolepis Cass.

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Gerard Nowak

2014-01-01

Full Text Available Differences in the composition of the "lactone fraction" of 4 species from the genus Chartolepis Cass. were observed. Cynaropierin was isolated from the above-ground parts of Chartolepis intermedia Boiss. and the occurrence there of grossheimin was confirmed. The following compounds were isolated from the above-ground parts of Chartolepis glastifolia (L. Cass.: centaurepensin, repin, cebellin C, acroptillin, cebellin D, cynaropicrin, cebellin F and janerin. Centaurepensin, repin, cebellin C, acroptillin, cynaropicrin, janerin and a new guaianolide, pterocaulin were isolated from the herb Chartolepis biebersteinii Jaub. et Spach. In addition to the lactones found in Chartolepis biebersteinii, Chartolepis pterocaula (Trautv. Czer. also accumulated grossheimin.

Cytotoxic sesquiterpene lactones from the aerial parts of Inula aucheriana.

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Ahmad Reza Gohari

2015-06-01

Full Text Available Inula aucheriana DC is a member of the family Asteraceae which is known to produce cytotoxic secondary metabolites noted as sesquiterpene lactones. In the present study, sesquiterpene lactones inuchinenolide B, 6-deoxychamissonolide (stevin and 14-acetoxy-1β,5α,7αH-4β-hydroxy-guai-9(10,11(13-dien-12,8α-olide were isolated from I. aucheriana. Inuchinenolide B and 14-acetoxy-1β,5α,7αH-4β-hydroxy-guai-9(10,11(13-dien-12,8α-olide were further evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay to demonstrate cytotoxic activity with IC50 values of (56.6, 19.0, (39.0, 11.8, and (55.7, 15.3 μg/mL against HepG-2, MCF-7 and A-549 cells, respectively. The cytotoxic activity of the two evaluated sesquiterpene lactones partly explains the cytotoxic activity that was previously observed for the extracts of Inula aucheriana. The isolated compounds could be further investigated in cancer research studies.

A Macrocyclic Peptide that Serves as a Cocrystallization Ligand and Inhibits the Function of a MATE Family Transporter

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Hiroaki Suga

2013-08-01

Full Text Available The random non-standard peptide integrated discovery (RaPID system has proven to be a powerful approach to discover de novo natural product-like macrocyclic peptides that inhibit protein functions. We have recently reported three macrocyclic peptides that bind to Pyrococcus furiosus multidrug and toxic compound extrusion (PfMATE transporter and inhibit the transport function. Moreover, these macrocyclic peptides were successfully employed as cocrystallization ligands of selenomethionine-labeled PfMATE. In this report, we disclose the details of the RaPID selection strategy that led to the identification of these three macrocyclic peptides as well as a fourth macrocyclic peptide, MaD8, which is exclusively discussed in this article. MaD8 was found to bind within the cleft of PfMATE’s extracellular side and blocked the path of organic small molecules being extruded. The results of an ethidium bromide efflux assay confirmed the efflux inhibitory activity of MaD8, whose behavior was similar to that of previously reported MaD5.

Natural and Synthetic Macrocyclic Inhibitors of the Histone Deacetylase Enzymes

DEFF Research Database (Denmark)

Maolanon, Alex; Kristensen, Helle; Leman, Luke

2017-01-01

Inhibition of histone deacetylase (HDAC) enzymes has emerged as a target for development of cancer chemotherapy. Four compounds have gained approval for clinical use by the Food and Drug Administration (FDA) in the US, and several are currently in clinical trials. However, none of these compounds...... HDAC enzymes may hold an advantage over traditional hydroxamic acid-containing inhibitors, which rely on chelation to the conserved active site zinc ion. Here, we review the literature on macrocyclic HDAC inhibitors obtained from natural sources and structure-activity relationship studies inspired...

Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng.

Science.gov (United States)

An, Ya-Nan; Zhang, Xue; Zhang, Tian-Yuan; Zhang, Meng-Yue; Qian-Zhang; Deng, Xiao-Yu; Zhao, Feng; Zhu, Ling-Juan; Wang, Guan; Zhang, Jie; Zhang, Yi-Xuan; Liu, Bo; Yao, Xin-Sheng

2016-06-08

Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1-5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS.

Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

DEFF Research Database (Denmark)

Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

2007-01-01

Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid...

A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf.

Science.gov (United States)

da Silva, Gustavo; Martinho, Ana; Soengas, Raquel González; Duarte, Ana Paula; Serrano, Rita; Gomes, Elsa Teixeira; Silva, Olga

2015-10-01

The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. The alkaloid revealed to be non-cytotoxic against both cell lines. The IC50 values from the cells were also determined. Copyright © 2015 Elsevier B.V. All rights reserved.

Squaraine rotaxanes with boat conformation macrocycles.

Science.gov (United States)

Fu, Na; Baumes, Jeffrey M; Arunkumar, Easwaran; Noll, Bruce C; Smith, Bradley D

2009-09-04

Mechanical encapsulation of fluorescent, deep-red bis(anilino)squaraine dyes inside Leigh-type tetralactam macrocycles produces interlocked squaraine rotaxanes. The surrounding macrocycles are flexible and undergo rapid exchange of chair and boat conformations in solution. A series of X-ray crystal structures show how the rotaxane co-conformational exchange process involves simultaneous lateral oscillation of the macrocycle about the center of the encapsulated squaraine thread. Rotaxane macrocycles with 1,4-phenylene sidewalls and 2,6-pyridine dicarboxamide bridging units are more likely to adopt boat conformations in the solid state than analogous squaraine rotaxane systems with isophthalamide-containing macrocycles. A truncated squaraine dye, with a secondary amine attached directly to the central C(4)O(2) core, is less electrophilic than the extended bis(anilino)squaraine analogue, but it is still susceptible to chemical and photochemical bleaching. Its stability is greatly enhanced when it is encapsulated as an interlocked squaraine rotaxane. An X-ray crystal structure of this truncated squaraine rotaxane shows the macrocycle in a boat conformation, and NMR studies indicate that the boat is maintained in solution. Encapsulation as a rotaxane increases the dye's brightness by a factor of 6. The encapsulation process appears to constrain the dye and reduce deformation of the chromophore from planarity. This study shows how mechanical encapsulation as a rotaxane can be used as a rational design parameter to fine-tune the chemical and photochemical properties of squaraine dyes.

Two lactones in the androconial scent of the lycaenid butterfly Celastrina argiolus ladonides

Science.gov (United States)

Ômura, Hisashi; Yakumaru, Kazuhisa; Honda, Keiichi; Itoh, Takao

2013-04-01

Male adult butterflies of many species have characteristic odors originating from the disseminating organs known as androconia. Despite the fact that androconia exist in several species, there have been few investigations on adult scents from the lycaenid species. Celastrina argiolus ladonides (Lycaenidae) is a common species in Eurasia. We have reported that male adults of this species emit a faint odor, and the major components causing this odor have been newly found in the Insecta. By using field-caught individuals, we determined the chemical nature and location of this odor in the butterfly. Gas chromatography-mass spectrometry (GC-MS) analyses revealed that two lactone compounds, lavender lactone and δ-decalactone, are present in the extracts of males but absent in those of the females. On an average, approximately 50 ng of each compound was found per male. Chiral GC analyses performed using enantiomerically pure standards revealed that the natural lavender lactone was a mixture of two enantiomers with an R/ S ratio of 32:68, whereas the natural δ-decalactone contained only the R-enantiomer. When the analyses were conducted using different parts—forewings, hindwings, and body—of three males, the lactones were more abundantly found on the forewings and hindwings than on the body. Microscopic observation of the wings demonstrated that battledore scales known as androconia are scattered on the upper surface of both the wings of C. argiolus ladonides males. These results indicate that the specialized scales on the wings of males serve as scent-disseminating organs.

Determination of Lactones in Wines by Headspace Solid-Phase Microextraction and Gas Chromatography Coupled with Mass Spectrometry

Directory of Open Access Journals (Sweden)

S. J. Pérez-Olivero

2014-01-01

Full Text Available Application of headspace solid-phase microextraction (HS-SPME coupled with high-resolution gas chromatographic (HRGC analysis was studied for determining lactones in wines. Six different SPME fibers were tested, and the influence of different factors such as temperature and time of desorption, ionic strength, time of extraction, content of sugar, ethanol, tannins and anthocyanins, and pH and influence of SO2 were studied. The proposed HS-SPME-GC method is an appropriate technique for the quantitative analysis of γ-butyrolactone, γ-hexalactone, trans-whiskey lactone, γ-octalactone, cis-whiskey lactone, γ-nonalactone, γ-decalactone, δ-decalactone, and γ-undecalactone in wines. Method reproducibility and repeatability ranged between 0.6 and 5.2% for all compounds. Detection limit for γ-butyrolactone was 0.17 mg/L and a few μg/L for the rest of the compounds. The optimized method has been applied to several wine samples.

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

Czech Academy of Sciences Publication Activity Database

Škorpilová, Ludmila; Rimpelová, S.; Jurášek, M.; Buděšínský, Miloš; Lokajová, Jana; Effenberg, R.; Slepička, P.; Ruml, T.; Kmoníčková, Eva; Drašar, P. B.; Wimmer, Zdeněk

2017-01-01

Roč. 13, JUL 4 (2017), s. 1316-1324 ISSN 1860-5397 R&D Projects: GA MŠk LD15012; GA MŠk(CZ) LO1304 Institutional support: RVO:61389030 ; RVO:61388963 ; RVO:68378041 Keywords : BODIPY conjugates * Cancer targeting * Drug delivery * Liposomes * Natural compounds * Sesquiterpene lactone trilobolide Subject RIV: CC - Organic Chemistry ; FR - Pharmacology ; Medidal Chemistry (UEM-P) OBOR OECD: Organic chemistry ; Pharmacology and pharmacy (UEM-P) Impact factor: 2.337, year: 2016

Simple Syntheses of Two New Benzo-Fused Macrocycles Incorporating Chalcone Moiety.

Science.gov (United States)

Mondal, Rina; Samanta, Swati; Sarkar, Saheli; Mallik, Asok K

2014-01-01

Simple syntheses of the benzo-fused 26-membered macrocyclic bischalcone (19E,43E)-2.11.27.36-tetroxaheptacyclo[44.4.0.0(4,9).0(12,17).0(21,26).0(29,34).0(37,42)]pentaconta-1(46),4(9),5,7,12(17),13,15,19,21,23,25,29,31,33,37,39,41,43,47,49-icosaene-18,45-dione (3) and the benzo-fused 13-membered macrocyclic chalcone (19E)-2.11-dioxatetracyclo[19.4.0.0(4,9).0(12,17)]pentacosa-1(25),4(9),5,7,12(17),13,15,19,21,23-decaen-18-one (5) using very common starting materials and reagents are described. The compounds are new and they have been characterized from their analytical and spectral data.

Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

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Andreas Speicher

2009-12-01

Full Text Available Macrocycles of the bisbibenzyl-type are natural products that are found exclusively in bryophytes (liverworts. The molecular framework of the subtype “isoplagiochin” is of substantial structural interest because of the chirality of the entire molecule, which arises from two biaryl axes in combination with two helical two-carbon units in a cyclic arrangement. From a structural as well as a synthetic point of view we report on the total synthesis of compounds which possess more rigid two-carbon biaryl bridges like stilbene (E or Z or even tolane moieties which were introduced starting with a Sonogashira protocol. The McMurry method proved to be a powerful tool for the cyclization to these considerably ring-strained macrocycles.

Use of a macrocyclic antibiotic as the chiral selector for enantiomeric separations by TLC

Energy Technology Data Exchange (ETDEWEB)

Armstrong, D.W.; Zhou, Y. (Univ. of Missouri, Rolla, MO (United States). Dept. of Chemistry)

1994-01-01

The macrocyclic antibiotic, vancomycin, was used as a chiral mobile phase additive for the thin layer chromatographic (TLC) resolution of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatized amino acids, racemic drugs and dansyl-amino acids. Excellent separations were achieved for most of these compounds in the reversed phase mode. Both the nature of the stationary phase and the composition of the mobile phase strongly influenced enantiomeric resolution. The best results were obtained using diphenyl stationary phases. Acetonitrile was the organic modifier that produced the most effective separations with the shortest development times. It is highly likely that macrocyclic antibiotics will play a major role in future enantiomeric separations.

Macrocyclic ligands and their use in chemical separations

International Nuclear Information System (INIS)

Izatt, R.M.; Bradshaw, J.S.; Bruening, R.L.; Krakowiak, K.E.; Tarbet, B.J.

1993-01-01

Macrocyclic chemistry has had a phenomenal growth curve during the past three decades (Izatt et al.). Interest in this field was catalyzed by Pedersen's report of the synthesis and partial characterization of a large number of novel cyclic polyethers. The unusual affinity of these new compounds for and selectivity among alkali metal cations was noted (Pedersen) and quantitated (Izatt et al.). A 1987 National Academy of Science publication on separations listed three high priority needs in the separations field (King). These were to develop highly selective reagents capable of discriminating among similar chemical species, reagents capable of concentrating trace amounts of solutes even in the presence of large excesses of matrix solutes, and reagents capable of removing solutes from large quantities of solvent. Certain macrocycles offer the promise of being successful in achieving all three of these goals. This promise arises from their high selectivity for particular cations in various series of closely related cations, their large affinities for particular cations, and the ease with which they can be modified to meet particular needs inherent to chemical separations

Sesquiterpene lactones and other chemical constituents of Mikania hoehnei R.

Directory of Open Access Journals (Sweden)

Chaves Juliana S.

2003-01-01

Full Text Available Phytochemical study of Mikania hoehnei yielded lupeyl acetate, stigmasterol, b-sitosterol, campesterol, b-sitosteryl glucopyranoside, stigmasteryl glucopyranoside, benzil 2,6-dimethoxybenzoate, luteolin, kaempferol and two sesquiterpene lactones: dehydrocostuslactone and 8b-hydroxyzaluzanin D. IR, ¹H and 13C NMR and MS spectroscopic analyses and comparisons with previously reported data were used for the identification of these compounds.

Confirmation of the definitive structure of Fleishmann`s lactone by NMR; Confirmacao da estrutura definitiva da lactona de Fleishmann por RMN

Energy Technology Data Exchange (ETDEWEB)

Figueroa Villar, Jose Daniel [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Secao de Quimica

1993-12-31

The reaction between 4-hydroxy-6-methyl-pyrone and ethyl-acetic-acetate produces a compound known since the beginning of the century, named Fleishman lactone in honor to its discover. The structure of this compound has been the aim of several researches due to its similarity with several poly-pyrones which are important in synthesis of important products. This work presents the accurate determination of the structure of the Fleishman lactone. The methodology is presented as well as confirmation tests 9 refs., 2 tabs.

Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Arun K.; Sean Fyvie, W.; Brindisi, Margherita; Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

2017-11-01

Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

Macrocyclic ligands for uranium complexation

International Nuclear Information System (INIS)

Potts, K.T.

1991-04-01

A highly preorganized 24-macrocycle containing biuret, thiobiuret and pyridine subunits has been prepared by high dilution ring-closure procedures. Intermediate products to this macrocycle have been utilized to extend this synthetic route to include further representatives where solubility and stability will be influenced by substituent variation. A 1:1 complex has been formed from uranyl acetate and a quinquepyridine derivative, this representing a new type of ligand for the uranyl ion. A very convenient synthetic procedure that will allow the incorporation of these macrocycles into polymeric systems has been developed for the introduction of a vinyl substituent into the 4-position of the pyridine ring. Using triflate, vinyltributyltin and Pd 0 chemistry, this procedure should make a variety of substituted 4-vinylpyridines available for the first time. 3 refs

Profiling acylated homoserine lactones in Yersinia ruckeri and influence of exogenous acyl homoserine lactones and known quorum-sensing inhibitors on protease production

DEFF Research Database (Denmark)

Kastbjerg, Vicky Gaedt; Nielsen, Kristian Fog; Dalsgaard, Inger

2007-01-01

produced at least eight different acylated homoserine lactones (AHLs) with N-(3-oxooctanoyl)-l-homoserine lactone (3-oxo-C8-HSL) being the dominant molecule. Also, some uncommon AHL, N-(3-oxoheptanoyl)-l-homoserine lactone (3-oxo-C7-HSL) and N-(3-oxononanoyl)-l-homoserine lactone (3-oxo-C9-HSL), were...

Free radical-scavenging delta-lactones from Boletus calopus.

Science.gov (United States)

Kim, Jin-Woo; Yoo, Ick-Dong; Kim, Won-Gon

2006-12-01

The methanol extracts from the fruiting body of the mushroom Boletus calopus showed free radical-scavenging activity. Bioactivity-guided fractionation of the methanol extracts led to a new hydroxylated calopin named calopin B, along with the known delta-lactones calopin and cyclocalopin A. The structure of the new calopin analogue was elucidated by spectroscopic methods. All compounds showed potent free radical-scavenging activity against superoxide, DPPH, and ABTS radicals with IC (50) values of 1.2 - 5.4 microg/mL.

Potent Antifouling Resorcylic Acid Lactones from the Gorgonian-Derived Fungus Cochliobolus lunatus

KAUST Repository

Shao, Chang Lun; Wu, Hui Xian; Wang, Chang Yun; Liu, Qing Ai; Xu, Ying; Wei, Mei Yan; Qian, Pei Yuan; Gu, Yu Cheng; Zheng, Cai Juan; She, Zhi Gang; Lin, Yong Cheng

2011-01-01

Three new 14-membered resorcylic acid lactones, two with a rare natural acetonide group and one with a 5-chloro-substituted lactone, named cochliomycins A-C (1-3), together with four known analogues, zeaenol (4), LL-Z1640-1 (5), LL-Z1640-2 (6), and paecilomycin F (7), were isolated from the culture broth of Cochliobolus lunatus, a fungus obtained from the gorgonian Dichotella gemmacea collected in the South China Sea. Their structures and the relative configurations of 1-3 were elucidated using comprehensive spectroscopic methods including NOESY spectra and chemical conversions. A transetherification reaction was also observed in which cochliomycin B (2) in a solution of CDCl3 slowly rearranged to give cochliomycin A (1) at room temperature. These resorcylic acid lactones were evaluated against the larval settlement of barnacle Balanus amphitrite, and antifouling activity was detected for the first time for this class of metabolites. The antibacterial and cytotoxic activities of these compounds were also examined. © 2011 The American Chemical Society and American Society of Pharmacognosy.

Potent Antifouling Resorcylic Acid Lactones from the Gorgonian-Derived Fungus Cochliobolus lunatus

KAUST Repository

Shao, Chang Lun

2011-04-25

Three new 14-membered resorcylic acid lactones, two with a rare natural acetonide group and one with a 5-chloro-substituted lactone, named cochliomycins A-C (1-3), together with four known analogues, zeaenol (4), LL-Z1640-1 (5), LL-Z1640-2 (6), and paecilomycin F (7), were isolated from the culture broth of Cochliobolus lunatus, a fungus obtained from the gorgonian Dichotella gemmacea collected in the South China Sea. Their structures and the relative configurations of 1-3 were elucidated using comprehensive spectroscopic methods including NOESY spectra and chemical conversions. A transetherification reaction was also observed in which cochliomycin B (2) in a solution of CDCl3 slowly rearranged to give cochliomycin A (1) at room temperature. These resorcylic acid lactones were evaluated against the larval settlement of barnacle Balanus amphitrite, and antifouling activity was detected for the first time for this class of metabolites. The antibacterial and cytotoxic activities of these compounds were also examined. © 2011 The American Chemical Society and American Society of Pharmacognosy.

Investigations on organogermanium compounds XII. Reactions of trialkylgermylalkalimetal compounds in hexamethylphosphoric triamide (HMPT) with some inorganic and organic compounds

NARCIS (Netherlands)

Bulten, E.J.; Noltes, J.G.

1971-01-01

Trialkylgermyl alkali metal compounds in HMPT have been found to be highly reactive nucleophiles. Reactions with some inorganic and organic compounds, such as oxygen, carbon dioxide, inorganic and orgaanic halides, aldehydes, ketones, epoxides and lactones are described. Several new

Sesquiterpene Lactone Composition and Cellular Nrf2 Induction of Taraxacum officinale Leaves and Roots and Taraxinic Acid β-d-Glucopyranosyl Ester.

Science.gov (United States)

Esatbeyoglu, Tuba; Obermair, Betina; Dorn, Tabea; Siems, Karsten; Rimbach, Gerald; Birringer, Marc

2017-01-01

Taraxacum officinale, the common dandelion, is a plant of the Asteraceae family, which is used as a food and medical herb. Various secondary plant metabolites such as sesquiterpene lactones, triterpenoids, flavonoids, phenolic acids, coumarins, and steroids have been described to be present in T. officinale. Dandelion may exhibit various health benefits, including antioxidant, anti-inflammatory, and anticarcinogenic properties. We analyzed the leaves and roots of the common dandelion (T. officinale) using high-performance liquid chromatography/mass spectrometry to determine its sesquiterpene lactone composition. The main compound of the leaf extract taraxinic acid β-d-glucopyranosyl ester (1), a sesquiterpene lactone, was isolated and the structure elucidation was conducted by nuclear magnetic resonance spectrometry. The leaf extract and its main compound 1 activated the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in human hepatocytes more significantly than the root extract. Furthermore, the leaf extract induced the Nrf2 target gene heme oxygenase 1. Overall, present data suggest that compound 1 may be one of the active principles of T. officinale.

Polymerization of 5-alkyl δ-lactones catalyzed by diphenyl phosphate and their sequential organocatalytic polymerization with monosubstituted epoxides

KAUST Repository

Zhao, Junpeng

2015-02-04

Organocatalytic ring-opening polymerization (ROP) reactions of three renewable 5-alkyl δ-lactones, namely δ-hexalactone (HL), δ-nonalactone (NL) and δ-decalactone (DL), using diphenyl phosphate (DPP) were investigated. Room temperature, together with a relatively high monomer concentration (≥3 M), was demonstrated to be suitable for achieving a living ROP behavior, a high conversion of the lactone, a controlled molecular weight and a low dispersity of the polyester. HL, containing a 5-methyl substituent, showed a much higher reactivity (polymerization rate) and a slightly higher equilibrium conversion than the compounds with longer alkyl substituents (NL and DL). The effectiveness of DPP-catalyzed ROP of 5-alkyl δ-lactones facilitated the one-pot performance following the t-BuP4-promoted ROP of monosubstituted epoxides. It has been shown in an earlier study that substituted polyethers acted as "slow initiators" for non-substituted lactones. However, efficient initiations were observed in the present study as substituted lactones were polymerized from the substituted polyethers. Therefore, this reinforces the previously developed "catalyst switch" strategy, making it a more versatile tool for the synthesis of well-defined polyether-polyester block copolymers from a large variety of epoxide and lactone monomers. © The Royal Society of Chemistry 2015.

Covalent Modification of Human Serum Albumin by the Natural Sesquiterpene Lactone Parthenolide

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Michael Plöger

2015-04-01

Full Text Available The reactivity of parthenolide (PRT, a natural sesquiterpene lactone from Tanacetum parthenium (Asteraceae, with human serum albumin (HSA was studied by UHPLC/+ESI-QqTOF MS analysis after tryptic digestion of albumin samples after incubation with this compound. It was found that the single free cysteine residue, C34, of HSA (0.6 mM reacted readily with PRT when incubated at approximately 13-fold excess of PRT (8 mM. Time-course studies with PRT and its 11β,13-dihydro derivative at equimolar ratios of the reactants revealed that PRT under the chosen conditions reacts preferably with C34 and does so exclusively via its α-methylene-γ-lactone moiety, while the epoxide structure is not involved in the reaction.

Creating molecular macrocycles for anion recognition

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Amar H. Flood

2016-03-01

Full Text Available The creation and functionality of new classes of macrocycles that are shape persistent and can bind anions is described. The genesis of triazolophane macrocycles emerges out of activity surrounding 1,2,3-triazoles made using click chemistry; and the same triazoles are responsible for anion capture. Mistakes made and lessons learnt in anion recognition provide deeper understanding that, together with theory, now provides for computer-aided receptor design. The lessons are acted upon in the creation of two new macrocycles. First, cyanostars are larger and like to capture large anions. Second is tricarb, which also favors large anions but shows a propensity to self-assemble in an orderly and stable manner, laying a foundation for future designs of hierarchical nanostructures.

A concise route to branched erythrono-gamma-lactones. Synthesis of the leaf-closing substance potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate

DEFF Research Database (Denmark)

Pedersen, Daniel Sejer; Robinson, Tony V; Taylor, Dennis K

2009-01-01

-94% yield), including the natural plant lactone (+/-)-2-C-d-methylerythrono-1,4-lactone 1. The latter compound was treated with aqueous potassium hydroxide to afford potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate 2, which is a leaf-closing substance of Leucaena leucocephalam....

Corymbiferan lactones from Penicillium hordei

DEFF Research Database (Denmark)

Overy, David Patrick; Blunt, J.W.

2004-01-01

Cultivation of a strain of Penicillium hordei on macerated tulip tissue agar resulted in the stimulated production of a series of four novel hydroxymethyl naphthalene carboxylic acid lactones from the fungus. The naphthalene derivatives were isolated using a combination of vacuum liquid chromatog......Cultivation of a strain of Penicillium hordei on macerated tulip tissue agar resulted in the stimulated production of a series of four novel hydroxymethyl naphthalene carboxylic acid lactones from the fungus. The naphthalene derivatives were isolated using a combination of vacuum liquid...... chromatography and preparative HPLC. Their structures were determined by 1D and 2D NMR techniques in conjunction with high-resolution electrospray mass spectrometry (HRESIMS). These metabolites were given the trivial names corymbiferan lactones A-D (1-4)....

Synthesis and antifungal activity of new bis-{gamma}-lactones analogous to avenaciolide

Energy Technology Data Exchange (ETDEWEB)

Magaton, Andreia da Silva; Rubinger, Mayura M. M.; Macedo Junior, Fernando C. de [Vicosa Univ., MG (Brazil). Dept. de Quimica]. E-mail: mayura@ufv.br; Zambolim, Laercio [Vicosa Univ., MG (Brazil). Dept. de Fitopatologia

2007-03-15

In a study of the antifungal activity of selected compounds as potentials agrochemicals, we have prepared and characterized by elemental analyses, infrared and NMR spectroscopies three new bis-{gamma}-lactones analogous to avenaciolide, where the octyl group of this natural product was replaced by heptyl, hexyl and pentyl groups. The effects on the mycelia development and conidia germination of Colletotrichum gloesporioides of these compounds and their synthetic precursors were evaluated in vitro. The title compounds were active in the tested conditions, while all the synthetic precursors were inactive. The preparation and characterization of 15 new synthetic intermediates are also described. (author)

The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

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Joscha Vollmeyer

2014-04-01

Full Text Available A series of shape-persistent phenylene–ethynylene–naphthylene–butadiynylene macrocycles with different extraannular alkyl groups and intraannular bridges is synthesized by oxidative Glaser-coupling of the appropriate precursors. The intraannular bridges serve in this case as templates that reduce the oligomerization even when the reaction is not performed under pseudo high-dilution conditions. The extraannular as well as the intraannular substituents have a strong influence on the thermal behavior of the compounds. With branched alkyl chains at the periphery, the macrocycles exhibit liquid crystalline (lc phases when the interior is empty or when the length of the alkyl bridge is just right to cross the ring. With a longer alkyl or an oligoethylene oxide bridge no lc phase is observed, most probably because the mesogene is no longer planar.

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

Science.gov (United States)

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

2016-08-01

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

Five new lactone derivatives from the stems of Dendrobium nobile.

Science.gov (United States)

Zhou, Xue-Ming; Zheng, Cai-Juan; Wu, Jia-Ting; Chen, Guang-Ying; Chen, Jun; Sun, Chong-Ge

2016-12-01

Five new lactone derivatives decumbic acids A and B (1 and 2), (-)-decumbic acid (3a), (-)- and (+)-dendrolactone (4a and 4b) together with four known compounds (3b and 5-7) were isolated from the stems of Dendrobium nobile. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 3a and 3b, 4a and 4b were isolated as two pair of enantiomers by chiral HPLC. The absolute configurations of 1, 2, 3a, 4a and 4b were determined by optical rotation and X-ray crystallographic analysis. The inhibitory activities of all compounds against nine phytopathogenic fungi and three cancer cell lines were evaluated. Copyright © 2016 Elsevier B.V. All rights reserved.

9-Hydroxyfurodysinin-O-ethyl Lactone: A New Sesquiterpene Isolated from the Tropical Marine Sponge Dysidea arenaria

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P. Karuso

2005-10-01

Full Text Available A new sesquiterpene, 9-hydroxyfurodysinin-O-ethyl lactone, has been isolated from a New Caledonian Dysidea arenaria, along with three known compounds. The possible incorporation of the ethyl ether from the extraction solvent is discussed.

STABILIZATION OF UNUSUAL SUBSTRATE COORDINATION MODES IN DINUCLEAR MACROCYCLIC COMPLEXES

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Vasile Lozan

2010-06-01

Full Text Available The steric protection offered by the macrobinucleating hexaazaditiophenolate ligand (L allows for the preparation of the first stable dinuclear nickel(II borohydride bridged complex, which reacts rapidly with elemental sulphur producing a tetranuclear nickel(II complex [{(LNi2}2(μ-S6]2+ bearing a helical μ4-hexa- sulfide ligand. The [(LCoII 2]2+ fragment have been able to trap a monomethyl orthomolybdate in the binding pocket. Unusual coordination modes of substrate in dinuclear macrocyclic compounds was demonstrated.

The synthesis of some unsaturated 4-substituted-g-lactones

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SUREN HUSINEC

2000-02-01

Full Text Available The synthesis of conjugated and nonconjugated unsaturated 4-substituted lactones of type 1 and 2 are described. The type 1 lactone was prepared by a two step procedure employing Bredereck's reagent. The type 2 lactone was synthesised by combining the Claisen-Ireland rearrangement and selenolactonisation.

Characterization and crystal structure of a 17-membered macrocyclic Schiff base compound MeO-sal-pn-bn

Czech Academy of Sciences Publication Activity Database

Khalaji, A.D.; Ghoran, S.H.; Rohlíček, Jan; Dušek, Michal

2015-01-01

Roč. 56, č. 2 (2015), s. 259-265 ISSN 0022-4766 Grant - others:AV ČR(CZ) Praemium Academiae Institutional support: RVO:68378271 Keywords : macrocyclic * Schiff base * spectroscopy * powder diffraction * orthorhombic Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.536, year: 2015

Two-Step Macrocycle Synthesis by Classical Ugi Reaction

NARCIS (Netherlands)

Abdelraheem, Eman M M; Khaksar, Samad; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; Shaabani, Shabnam; Dömling, Alexander

2018-01-01

The direct nonpeptidic macrocycle synthesis of α-isocyano-ω-amines via the classical Ugi four-component reaction (U-4CR) is introduced. Herein an efficient and flexible two-step procedure to complex macrocycles is reported. In the first step, the reaction between unprotected diamines and

Rhodococcus erythropolis and Its γ-Lactone Catabolic Pathway: An Unusual Biocontrol System That Disrupts Pathogen Quorum Sensing Communication

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Xavier Latour

2013-12-01

Full Text Available Rhodococcus erythropolis is an environmental Gram-positive Actinobacterium with a versatile metabolism involved in various bioconversions and degradations. Rhodococci are best known for their great potential in numerous decontamination and industrial processes. However, they can also prevent plant disease by disrupting quorum sensing-based communication of Gram-negative soft-rot bacteria, by degrading N-acyl-homoserine lactone signaling molecules. Such biocontrol activity results partly from the action of the γ-lactone catabolic pathway. This pathway is responsible for cleaving the lactone bond of a wide range of compounds comprising a γ-butyrolactone ring coupled to an alkyl or acyl chain. The aliphatic products of this hydrolysis are then activated and enter fatty acid metabolism. This short pathway is controlled by the presence of the γ-lactone, presumably sensed by a TetR-like transcriptional regulator, rather than the presence of the pathogen or the plant-host in the environment of the Rhodococci. Both the density and biocontrol activity of R. erythropolis may be boosted in crop systems. Treatment with a cheap γ-lactone stimulator, for example, the food flavoring γ-caprolactone, induces the activity in the biocontrol agent, R. erythropolis, of the pathway degrading signaling molecules; such treatments thus promote plant protection.

Novel macrocyclic carriers for proton-coupled liquid membrane transport. Final report

Energy Technology Data Exchange (ETDEWEB)

Lamb, J.D.; Izatt, R.M.; Bradshaw, J.S.; Shirts, R.B.

1996-08-24

The objective of this research program is to elucidate the chemical principles which are responsible for the cation selectivity and permeability of liquid membranes containing macrocyclic carriers. Several new macrocyclic carriers were synthesized during the last three year period. In addition, new, more convenient synthetic routes were achieved for several nitrogen-containing bicyclic and tricyclic macrocycles. The cation binding properties of these macrocycles were investigated by potentiometric titration, calorimetric titration, solvent extraction and NMR techniques. In addition, hydrophobic macrocycles were incorporated into dual hollow fiber and other membrane systems to investigate their membrane performance, especially in the proton-coupled transport mode. A study of the effect of methoxyalkyl macrocycle substituents on metal ion transport was completed. A new calorimeter was constructed which made it possible to study the thermodynamics of macrocycle-cation binding to very high temperatures. Measurements of thermodynamic data for the interaction of crown ethers with alkali and alkaline earth cations were achieved to 473 K. Molecular modeling work was begun for the first time on this project and fundamental principles were identified and developed for the establishment of working models in the future.

Determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin in human plasma by sensitive high-performance liquid chromatography with fluorescence detection

NARCIS (Netherlands)

W.J. Loos (Walter); A. Sparreboom (Alex); J. Verweij (Jaap); K. Nooter (Kees); G. Stoter (Gerrit); J.H.M. Schellens (Jan)

1997-01-01

textabstractTwo sensitive reversed-phase high-performance liquid chromatographic fluorescence methods, with simple sample handling at the site of the patient, are described for the determination of the lactone and lactone plus carboxylate forms of g-aminocamptothecin (9AC). For 9AC lactone, the

Anthelmintic-resistant nematodes in Irish commercial sheep flocks- the state of play

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Good Barbara

2012-12-01

Full Text Available Abstract Anthelmintic resistance has been reported in most sheep producing countries. Prior to the mid 1990s, reports of anthelmintic resistance in Ireland were sparse and focused on benzimidazole, one of the three classes of anthelmintic available during this period. This evidence for efficacy issues on Irish farms combined with awareness that anthelmintic resistance was increasingly being reported in other countries prompted the need for more comprehensive investigations on Irish farms. Faecal egg count reduction and micro-agar larval development tests were employed to investigate resistance to benzimidazole, levamisole and macrocyclic lactone. There is compelling evidence for resistance to both benzimidazole (>88% of flocks and levamisole (>39% of flocks. Resistance of nematode populations to macrocyclic lactone was suspected on a small number of farms (11% but needs to be confirmed. The recent introduction of two new classes of anthelmintics, after over a 25 year interval, together with the evidence that anthelmintic resistance is reported within a relatively short time following the introduction of a new anthelmintic compound means that the challenge to the industry is immediate. Actions are urgently required to manage anthelmintic resistance so as to prolong the lifespan of anthelmintics.

In Vitro Antitumor Activity of Sesquiterpene Lactones from Lychnophora trichocarpha

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D.A. Saúde-Guimarães

2014-06-01

Full Text Available The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae, which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA, against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50 for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.

The coordination chemistry of macrocyclic ligands II

International Nuclear Information System (INIS)

Klimes, J.; Knoechel, A.; Rudolph, G.

1977-01-01

Compounds of UO 2 (NO 3 ) 2 .6H 2 0 or Th(NO 3 ) 4 .5H 2 0 with five selected crown ethers were prepared according to the method described in Knoeckel et al., Inorg.Nucl.Chem.Lett.; 11:787 (1975). The products were characterized by chemical analysis, NMR, IR and Raman spectroscopy. The results are analyzed and discussed. It is shown that the NO 3 groups remain free after combination, and the H 2 0 groups form the bonds to the polyether. It is concluded that the polyether molecule is attached to two units of UO 2 (NO 3 ) 2 .2H 2 0 (or Th(NO 3 ) 4 .3H 2 0), one each side of the polyether. This would be contrary to the assumption in previous publications, that the U0 2 2+ and Th 4+ ions were coordinated inside the macrocyclic ligand structure. The present hypothesis, however, agrees with a recently published x-ray structure for the uranium compound. In view of the new proposed structure it is suggested that the compounds should be regarded as adducts rather than complexes. (U.K.)

Synthesis and antifungal activity of halogenated aromatic bis-γ-lactones analogous to avenaciolide

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Pedro A. Castelo-Branco

2012-01-01

Full Text Available Here we describe the total syntheses and characterization by elemental analyses, infrared and NMR spectroscopy of three new compounds analogous to avenaciolide, a bis-γ-lactone isolated from Aspergillus avenaceus that possesses antifungal activity, where the octyl group of the natural product was replaced by aromatic groups containing chlorine and fluorine atoms. The effects of the avenaciolide, the novel compounds and their synthetic precursors on mycelia development and conidia germination of Colletotrichum gloeosporioides and Fusarium solani were evaluated in vitro. The title compounds were almost as active as avenaciolide. The absolute structures of the chlorinated analogs were determined by X-ray diffraction analysis.

A general strategy for synthesis of cyclophane-braced peptide macrocycles via palladium-catalysed intramolecular sp3 C-H arylation

Science.gov (United States)

Zhang, Xuekai; Lu, Gang; Sun, Meng; Mahankali, Madhu; Ma, Yanfei; Zhang, Mingming; Hua, Wangde; Hu, Yuting; Wang, Qingbing; Chen, Jinghuo; He, Gang; Qi, Xiangbing; Shen, Weijun; Liu, Peng; Chen, Gong

2018-05-01

New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein-protein interactions. Here, we report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)-H arylation reactions. Easily accessible linear peptide precursors of simple and versatile design can be selectively cyclized at the side chains of either aromatic or modified non-aromatic amino acid units to form various cyclophane-braced peptide cycles. This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures. Preliminary cell proliferation screening of the pilot library revealed a potent lead compound with selective cytotoxicity toward proliferative Myc-dependent cancer cell lines.

Macrocyclic complexes of radionuclides in nuclear medicine

International Nuclear Information System (INIS)

Majkowska, A.; Bilewicz, A.

2008-01-01

The use of radiometal-labeled small complexes and biomolecules as diagnostic and therapeutic agents is a relatively new area of medical research. Radiopharmaceuticals are radiolabeled molecules designed to deliver ionizing radiation doses to specific disease sites. Between the targeting biomolecule and a radionuclide a bifunctional ligand is inserted, one end of which is covalently attached to the targeting molecule either directly or through a linker whereas the other strongly coordinates a metallic radionuclide. Selection of a bifunctional ligand is largely determined by the nature and oxidation state of a metal ion. The metal chelate can significantly affect the tumor uptake and biodistribution of radiopharmaceuticals based on small biomolecules. This is because in many cases the metal chelate contributes greatly to the overall size and lipophilicity of the radiopharmaceutical. Therefore, the design and selection of the ligand is very important for the development of a clinically useful therapeutic agent. The requirement for high thermodynamic and kinetic stability of the metal complex is often achieved through the use of macrocyclic ligands with a functionalized arm for covalent bonding to the biomolecule. In this review synthesis of bifunctional macrocyclic ligands and properties of radionuclide macrocyclic complexes used in nuclear medicine are presented. We describe results in two areas: substituted macrocyclic aza ligands for chelation of hard metal cations, and macrocycles containing sulphur for complexation of soft metal cations. Special attention was paid to stability of the complexes as well as to their lipophilicity, which affect biological properties of the formed radiopharmaceuticals. We also include a forecast of the near-term opportunities that are likely to determine practice in the next few years. (authors)

Sesquiterpene lactones. XXIII. Isolation of sesquiterpene lactones from Centaurea L. species

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Barbara Geppert

2014-01-01

Full Text Available Sesquiterpene lactones were isolated from 18 species or subspecies of the genus Centaurea L.: salonitenolide (I was found in C. crithmifolia Vis., C. friderici Vis., C, paniculata L., C. calcitrapa L., C. pontica Prodan et E. L' Nyarady, C. eriophora L., C. alba L. subsp. deusta (Ten. Nyman, C. alba L. subsp. caliacrae (Prodan Dostal and C. weldeniana Reichenb.; cnicin (II was found in: C. vallesiaca (DC. Jordan, C. calcitrapa L., C. aspera L. subsp. aspera, C. sphaerocephala L. subsp. lusitanica (Boiss. et Reuter Nyman, C. sulphurea Willd., C. eriophora L. and C. rocheliana (Heuffel Dostal; cynaropicrin (III was detected in C. debeauxii Gren. et Gordon subsp. thuillieri Dostal; acroptillin (V, repin (VI and janerin (VII in C. bella Trautv. Other unidentified sesquiterpene lactones were also found to be present in the examined plants.

Rubrolides as model for the development of new lactones and their aza analogs as potential photosynthesis inhibitors.

Science.gov (United States)

Pereira, Ulisses A; Barbosa, Luiz C A; Demuner, Antônio J; Silva, Antônio A; Bertazzini, Michele; Forlani, Giuseppe

2015-07-01

Natural phytotoxins and their synthetic analogs are a potential source of new bioactive compounds for agriculture. Analogs of rubrolides, a class of γ-alkylidene-γ-lactones isolated from different ascidians, have been shown to interfere with the photosynthetic electron-transport chain, yet their activity needs to be improved. With this aim, ten 5-aryl-6-benzyl-4-bromopyridazin-3(2H)-ones were prepared in yields ranging from 44 to 88% by reaction of their correspondent γ-alkylidene-γ-lactones with NH2 NH2 . The structures of these rubrolide analogs were determined by (1) H- and (13) C-NMR, 2D-NMR (COSY and HETCOR), NOE difference, and MS techniques. These compounds were evaluated for their abilities of interfering with the light-driven reduction of ferricyanide by isolated spinach chloroplasts. Lactones with electron-withdrawing substituents in the para-position of the benzylidene ring were the most effective inhibitors. Characterization of the activity of 11b/11b' suggested a mechanism based on the interaction with the plastoquinone binding site of photosystem II. Addition of several compounds to the culture medium of a cyanobacterial model strain was found to inhibit algal growth. However, the relative effectiveness was not consistent with their activity in vitro, suggesting the occurrence of multiple targets and/or detoxyfication mechanisms. Indeed, the compounds showed differential effects on the heterotrophic growth of some crop species, Cucumis sativus and Sorghum bicolor. Pyridazin-3(2H)-ones 12e, 12i, and 12j, which have been found poorly active against the photosynthetic electron transport, were the most effective in inhibiting the growth of some weeds, Ipomoea grandifolia and Brachiaria decumbens, under greenhouse conditions. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi.

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Valeria P Sülsen

Full Text Available Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin

Macrocyclic bis(ureas as ligands for anion complexation

Directory of Open Access Journals (Sweden)

Claudia Kretschmer

2014-08-01

Full Text Available Two macrocyclic bis(ureas 1 and 2, both based on diphenylurea, have been synthesized. Compound 1 represents the smaller ring with two ethynylene groups as linkers and 2 the larger ring with two butadiynylene groups. On thermal treatment to 130 °C molecule 1 splits up into two dihydroindoloquinolinone (3 molecules. Both compounds 1 and 2 form adducts with polar molecules such as dimethyl sulfoxide (DMSO and dimethylformamide (DMF and act as complexing agents towards a series of anions (Cl−, Br−, I−, NO3−, HSO4−. The crystal structures of 3, 2·2DMSO, 2·2DMF, and of the complex NEt4[Br·2] have been determined. Quantitative investigations of the complexation equilibria were performed via 1H NMR titrations. While 1 is a rather weak complexing agent, the large ring of 2 binds anions with association constants up to log K = 7.93 for chloride ions.

Production of acylated homoserine lactones by different serotypes of Vibrio anguillarum both in culture and during infection of rainbow trout

DEFF Research Database (Denmark)

Buch, C.; Sigh, J.; Nielsen, J.

2003-01-01

Onehundred and forty-eight out of onehundred and fifty strains of Vibrio anguillarum isolated from vibriosis in Danish marine aquaculture produced bacterial communication signals, acylated homoserine lactones, eliciting a response in the Agrobacterium tumefaciens (pZLR4) monitoring system. One...... strain, a serotype O4, induced a strong response in the Chromobacterium violaceum (CV026) monitoring system. Profiles of AHLs determined by TLC separation revealed the presence of at least four AHLs and a compound similar to N-3-oxo-decanoyl homoserine lactone (3-oxo-C10-HSL) was present in all strains...

Macrocyclic ligands for uranium complexation: Progress report, August 15, 1987-present

International Nuclear Information System (INIS)

Potts, K.T.

1988-03-01

The synthesis of several macrocyclic ligands, designed by a computer modeling approach for the complexation of the uranyl ion, has now been completed and their structures established. Preliminary indicate that these macrocycles successfully complex the uranyl ion. Other synthetic efforts have led to a variety of intermediates suitable for final ring closure to the desired macrocycles, providing appreciable potential for variation of the macrocyclic peripheral atoms. A 1:1-uranyl ion complex of one of these precursor products has been shown to undergo a DMSO-induced rearrangement to a 2:1 uranyl ion to ligand complex, both structures having been established by single crystal x-ray data. 10 refs

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments.

Science.gov (United States)

Almeida, Macia C S DE; Souza, Luciana G S; Ferreira, Daniele A; Pinto, Francisco C L; Oliveira, Débora R DE; Santiago, Gilvandete M P; Monte, Francisco J Q; Braz-Filho, Raimundo; Lemos, Telma L G DE

2017-01-01

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

Dehydrocostus lactone is exuded from sunflower roots and stimulates germination of the root parasite Orobanche cumana.

Science.gov (United States)

Joel, Daniel M; Chaudhuri, Swapan K; Plakhine, Dina; Ziadna, Hammam; Steffens, John C

2011-05-01

The germination of the obligate root parasites of the Orobanchaceae depends on the perception of chemical stimuli from host roots. Several compounds, collectively termed strigolactones, stimulate the germination of the various Orobanche species, but do not significantly elicit germination of Orobanche cumana, a specific parasite of sunflower. Phosphate starvation markedly decreased the stimulatory activity of sunflower root exudates toward O. cumana, and fluridone - an inhibitor of the carotenoid biosynthesis pathway - did not inhibit the production of the germination stimulant in both shoots and roots of young sunflower plants, indicating that the stimulant is not a strigolactone. We identified the natural germination stimulant from sunflower root exudates by bioassay-driven purification. Its chemical structure was elucidated as the guaianolide sesquiterpene lactone dehydrocostus lactone (DCL). Low DCL concentrations effectively stimulate the germination of O. cumana seeds but not of Phelipanche aegyptiaca (syn. Orobanche aegyptiaca). DCL and other sesquiterpene lactones were found in various plant organs, but were previously not known to be exuded to the rhizosphere where they can interact with other organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Highly Functionalised Cyclopentanes by Radical Cyclisation of Unsaturated Bromolactones III. Preparation of Carbaaldohexofuranoses. - Determination of the Relative Configuration at C-4/C-5 of 2,3-Unsaturated heptono-1,4-lactones by Means of 1-H NMR Spectroscopy

DEFF Research Database (Denmark)

Lundt, Inge; Horneman, Anne Marie

1999-01-01

Two new carbaaldohexofuranoses, carba--D-glucofuranose and carba--L-mannofuranose have been prepared using 5,6-O-isopropylidene-D-glycero-L-galacto-heptono-1,4-lactone (6) as the starting material. The key step was a highly stereoselective intramolecular 5-exo-trig radical cyclisation of C-2......-substituted 2,3-unsaturated 7-bromo-7-deoxy-heptono-1,4-lactones promoted by tributyltin hydride. Assignment of the configuration of the unsaturated lactones was based upon NMR data of related compounds. The starting material, compound 6, was obtained by chain elongation of D-gulose, and a facile method...

Biosynthesis of macrocyclic diterpenoids in Euphorbia lathyris L

DEFF Research Database (Denmark)

Luo, Dan

documents the investigation of the biosynthetic pathways of macrocyclic diterpenoids known as Euphorbia factors in Euphorbia lathyris L. (caper spurge). These macrocyclic diterpenoids are the current industrial source of ingenol mebutate, which is approved for the treatment of actinic keratosis...

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete "1H and "1"3C chemical shift assignments

International Nuclear Information System (INIS)

Almeida, Macia C.S. de; Souza, Luciana G.S.; Ferreira, Daniele A.; Pinto, Francisco C.L.; Santiago, Gilvandete M.P.; Monte, Francisco J.Q.; Lemos, Telma L.G.; Oliveira, Debora R. de; Braz-Filho, Raimundo

2017-01-01

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the "1H and "1"3C NMR spectra. (author)

On-Surface Synthesis and Characterization of Honeycombene Oligophenylene Macrocycles.

Science.gov (United States)

Chen, Min; Shang, Jian; Wang, Yongfeng; Wu, Kai; Kuttner, Julian; Hilt, Gerhard; Hieringer, Wolfgang; Gottfried, J Michael

2017-01-24

We report the on-surface formation and characterization of [30]-honeycombene, a cyclotriacontaphenylene, which consists of 30 phenyl rings (C 180 H 120 ) and has a diameter of 4.0 nm. This shape-persistent, conjugated, and unsubstituted hexagonal hydrocarbon macrocycle was obtained by solvent-free synthesis on a silver (111) single-crystal surface, making solubility-enhancing alkyl side groups unnecessary. Side products include strained macrocycles with square, pentagonal, and heptagonal shape. The molecules were characterized by scanning tunneling microscopy and density functional theory (DFT) calculations. On the Ag(111) surface, the macrocycles act as molecular quantum corrals and lead to the confinement of surface-state electrons inside the central cavity. The energy of the confined surface state correlates with the size of the macrocycle and is well described by a particle-in-the-box model. Tunneling spectroscopy suggests conjugation within the planar rings and reveals influences of self-assembly on the electronic structure. While the adsorbed molecules appear to be approximately planar, the free molecules have nonplanar conformation, according to DFT.

Macrocyclic G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, M C; Ulven, Trond

2010-01-01

are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds† †Electronic supplementary information (ESI) available: Experimental procedures, characterization data and details of the computational analyses. See DOI: 10.1039/c5ob00371g Click here for additional data file.

Science.gov (United States)

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R. J. D.; Giacomini, Elisa; Hansen, Mette R.; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F.

2015-01-01

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity. PMID:25778821

Production of acyl-homoserine lactone quorum-sensing signals is widespread in gram-negative Methylobacterium.

Science.gov (United States)

Poonguzhali, Selvaraj; Madhaiyan, Munusamy; Sa, Tongmin

2007-02-01

Members of Methylobacterium, referred as pink-pigmented facultative methylotrophic bacteria, are frequently associated with terrestrial and aquatic plants, tending to form aggregates on the phyllosphere. We report here that the production of autoinducer molecules involved in the cell-to-cell signaling process, which is known as quorum sensing, is common among Methylobacterium species. Several strains of Methylobacterium were tested for their ability to produce N-acyl-homoserine lactone (AHL) signal molecules using different indicators. Most strains of Methylobacterium tested could elicit a positive response in Agrobacterium tumefaciens harboring lacZ fused to a gene that is regulated by autoinduction. The synthesis of these compounds was cell-density dependent, and the maximal activity was reached during the late exponential to stationary phases. The bacterial extracts were separated by thin-layer chromatography and bioassayed with A. tumefaciens NT1 (traR, tra::lacZ749). They revealed the production of various patterns of the signal molecules, which are strain dependent. At least two signal molecules could be detected in most of the strains tested, and comparison of their relative mobilities suggested that they are homologs of N-octanoyl-DL-homoserine lactone (C8-HSL) and N-decanoyl-DL-homoserine lactone (C10-HSL).

Synthesis of antirrhinolide, a new lactone from Antirrhinum majus

DEFF Research Database (Denmark)

Franzyk, Henrik; Frederiksen, Signe Maria; Jensen, Søren Rosendal

1998-01-01

In addition to the known iridoid glucosides antirrhinoside (1), antirrhide (3), antirrhinoside (1), linarioside (5) and chaenorrhinoside (6), a novel nonglucosidic iridoid lactone was isolated in trace amount from Antirrhinum majus (Scrophulariaceae). This lactone, named antirrhinolide (4a...

Accurate and Reliable Prediction of the Binding Affinities of Macrocycles to Their Protein Targets.

Science.gov (United States)

Yu, Haoyu S; Deng, Yuqing; Wu, Yujie; Sindhikara, Dan; Rask, Amy R; Kimura, Takayuki; Abel, Robert; Wang, Lingle

2017-12-12

Macrocycles have been emerging as a very important drug class in the past few decades largely due to their expanded chemical diversity benefiting from advances in synthetic methods. Macrocyclization has been recognized as an effective way to restrict the conformational space of acyclic small molecule inhibitors with the hope of improving potency, selectivity, and metabolic stability. Because of their relatively larger size as compared to typical small molecule drugs and the complexity of the structures, efficient sampling of the accessible macrocycle conformational space and accurate prediction of their binding affinities to their target protein receptors poses a great challenge of central importance in computational macrocycle drug design. In this article, we present a novel method for relative binding free energy calculations between macrocycles with different ring sizes and between the macrocycles and their corresponding acyclic counterparts. We have applied the method to seven pharmaceutically interesting data sets taken from recent drug discovery projects including 33 macrocyclic ligands covering a diverse chemical space. The predicted binding free energies are in good agreement with experimental data with an overall root-mean-square error (RMSE) of 0.94 kcal/mol. This is to our knowledge the first time where the free energy of the macrocyclization of linear molecules has been directly calculated with rigorous physics-based free energy calculation methods, and we anticipate the outstanding accuracy demonstrated here across a broad range of target classes may have significant implications for macrocycle drug discovery.

Allergenic sesquiterpene lactones from cushion bush (Leucophyta brownii Cass.)

DEFF Research Database (Denmark)

Paulsen, Evy; Gade Hyldgaard, Mette; Andersen, Klaus E.

2017-01-01

BACKGROUND: The Australian cushion bush (Leucophyta brownii) of the Compositae family of plants has become a popular pot and container plant. The plant produces the sesquiterpene lactone allergen calocephalin. OBJECTIVES: To assess the sensitizing potential of sesquiterpene lactones from cushion ...

Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).

Science.gov (United States)

Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M

2015-11-02

Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety.

A validated Fourier transform infrared spectroscopy method for quantification of total lactones in Inula racemosa and Andrographis paniculata.

Science.gov (United States)

Shivali, Garg; Praful, Lahorkar; Vijay, Gadgil

2012-01-01

Fourier transform infrared (FT-IR) spectroscopy is a technique widely used for detection and quantification of various chemical moieties. This paper describes the use of the FT-IR spectroscopy technique for the quantification of total lactones present in Inula racemosa and Andrographis paniculata. To validate the FT-IR spectroscopy method for quantification of total lactones in I. racemosa and A. paniculata. Dried and powdered I. racemosa roots and A. paniculata plant were extracted with ethanol and dried to remove ethanol completely. The ethanol extract was analysed in a KBr pellet by FT-IR spectroscopy. The FT-IR spectroscopy method was validated and compared with a known spectrophotometric method for quantification of lactones in A. paniculata. By FT-IR spectroscopy, the amount of total lactones was found to be 2.12 ± 0.47% (n = 3) in I. racemosa and 8.65 ± 0.51% (n = 3) in A. paniculata. The method showed comparable results with a known spectrophotometric method used for quantification of such lactones: 8.42 ± 0.36% (n = 3) in A. paniculata. Limits of detection and quantification for isoallantolactone were 1 µg and 10 µg respectively; for andrographolide they were 1.5 µg and 15 µg respectively. Recoveries were over 98%, with good intra- and interday repeatability: RSD ≤ 2%. The FT-IR spectroscopy method proved linear, accurate, precise and specific, with low limits of detection and quantification, for estimation of total lactones, and is less tedious than the UV spectrophotometric method for the compounds tested. This validated FT-IR spectroscopy method is readily applicable for the quality control of I. racemosa and A. paniculata. Copyright © 2011 John Wiley & Sons, Ltd.

60Co γ-irradiation effects on electrical properties of a rectifying diode based on a novel macrocyclic Zn octaamide complex

International Nuclear Information System (INIS)

Ocak, Y.S.; Kilicoglu, T.; Topal, G.; Baskan, M.H.

2010-01-01

C 36 H 28 N 12 O 8 ZnCl 2 .9/2H 2 O, Zn-octaamide (ZnOA) macrocyclic compound was synthesized to be used in the fabrication of electronic and photoelectronic devices. The structure of new compound was identified by using 1 H NMR, 13 C NMR, IR, UV-vis and LC-MS spectroscopic methods. The Sn/ZnOA/n-Si/Au structure was engineered by forming a thin macrocyclic organic compound layer on n-Si inorganic substrate and then by evaporating Sn metal on the organic layer. It was seen that the device had a good rectifying behaviour and showed Schottky diode properties. The diode was irradiated under 60 Co γ-source at room temperature. Characteristic parameters of the diode were determined from its current-voltage (I-V) and capacitance voltage (C-V) measurements before and after irradiation. It was observed that γ-irradiation had clear effects on I-V and C-V properties. Also, it was seen that the barrier height, the ideality factor and the series resistance values decreased after the applied radiation, while the saturation current value increased.

Hydrolyzable tannins of tamaricaceous plants. V. Structures of monomeric-trimeric tannins and cytotoxicity of macrocyclic-type tannins isolated from Tamarix nilotica (1).

Science.gov (United States)

Orabi, Mohamed A A; Taniguchi, Shoko; Sakagami, Hiroshi; Yoshimura, Morio; Yoshida, Takashi; Hatano, Tsutomu

2013-05-24

Three new ellagitannin monomers, nilotinins M5-M7 (1-3), a dimer, nilotinin D10 (4), and a trimer, nilotinin T1 (5), together with three known dimers, hirtellin D (7) and tamarixinins B (8) and C (9), and a trimer, hirtellin T2 (6), were isolated from Tamarix nilotica dried leaves. The structures of the tannins were elucidated by intensive spectroscopic methods and chemical conversions into known tannins. The new trimer (5) is a unique macrocyclic type whose monomeric units are linked together by an isodehydrodigalloyl and two dehydrodigalloyl moieties. Additionally, dimeric and trimeric macrocyclic-type tannins isolated from T. nilotica in this study were assessed for possible cytotoxic activity against four human tumor cell lines. Tumor-selective cytotoxicities of the tested compounds were higher than those of synthetic and natural potent cytotoxic compounds, including polyphenols, and comparable with those of 5-fluorouracil and melphalan.

Derivatized Pentadentate Macrocyclic Ligands and Their Transition Metal Complexes

Directory of Open Access Journals (Sweden)

Muhammad S. Khan

2002-06-01

Full Text Available The reaction of the pendant hydroxyethyl group in the planar pentadentate macrocyclic ligand,1,11-bis(2’-hydroxyethyl-4,8;12,16;17,21-trinitrilo-1,2,10,11-tetraazacyclohenicosa- 2,4,6,9,12,14,18,20-octaene (L2, derived from the condensation of 2,6-pyridinedialdehyde with 6,6’-bis(2’ hydroxyethylhydrazino -2,2’-bipyridine (L1, has been investigated. Esterification reactions are facile, and the reaction of the hydroxyethyl-substituted macrocycle with thionyl chloride yields a chloroethyl derivative. Metal complexes of the new derivatized macrocyclic ligands L3-6having general formula ML3-6X2.nH2O (M = Mn, Fe, Co, Ni, Cu, Zn are readily prepared.

Molecular and vibrational structure of the extracellular bacterial signal compound N-butyryl-homoserine lactone (C4-HSL)

DEFF Research Database (Denmark)

Bak, Jimmy; Spanget-Larsen, Jens

2009-01-01

contributions from suspended micro-crystalline aggregates and dissolved monomeric species. The key vibrational bands of the monomeric form of C4-HSL are reported here for the first time: 3425cm−1 (ν(N-H)), 1784cm−1 (ν(C&dbnd;O), lactone), 1688cm−1 (amide I), and 1494cm−1 (amide II) (CCl4)....

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete {sup 1}H and {sup 13}C chemical shift assignments

Energy Technology Data Exchange (ETDEWEB)

Almeida, Macia C.S. de; Souza, Luciana G.S.; Ferreira, Daniele A.; Pinto, Francisco C.L.; Santiago, Gilvandete M.P.; Monte, Francisco J.Q.; Lemos, Telma L.G., E-mail: fmonte@dqoi.ufc.br [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil); Oliveira, Debora R. de; Braz-Filho, Raimundo [Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropedica, RJ (Brazil). Departamento de Quimica

2017-09-01

A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the {sup 1}H and {sup 13}C NMR spectra. (author)

The quorum-quenching N-acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket

NARCIS (Netherlands)

Bokhove, Marcel; Jimenez, Pol Nadal; Quax, Wim J.; Dijkstra, Bauke W.

2010-01-01

In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as N-acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e. g., lactonases or amidohydrolases abolishes AHL

Screening Some Plants for their Antiproliferative Compounds

Directory of Open Access Journals (Sweden)

Ufuk Kolak

2012-03-01

Full Text Available This paper covers the screening of the secondary plant products to find a cure against cancer which were piled up during the years. In early stages of these studies highly active antitumor glycoproteins were obtained from native Arizona (USA plants. Later smaller molecules were isolated showing antitumor activity in different test systems. Among these compounds sesquiterpene lactones with an exo-methylene group in the lactone ring, unsaturated diterpenoids and some triterpenoids exhibited activity in vivo and in vitro test systems. A few Colchicum alkaloids showed high activity against murine lymphocytic leukemia (P388. Activity also established in some flavonoidal compounds. Today all around the world research on Natural Products is still going on.

Quorum sensing signal molecules (acylated homoserine lactones) in Gram-negative fish pathogenic bacteria

DEFF Research Database (Denmark)

Bruhn, Jesper Bartholin; Dalsgaard, Inger; Nielsen, K.F.

2005-01-01

The aim of the present study was to investigate the production of quorum sensing signals (specifically acylated homoserine lactones, AHLs) among a selection of strains of Gram-negative fish bacterial pathogens. These signals are involved in the regulation of virulence factors in some human...... salmonicida and Vibrio splendidus were also positive. Aeromonas species produced N-butanoyl homoserine lactone (BHL) and N-hexanoyl homoserine lactone (HHL) and 1 additional product, whereas N-3-oxo-hexanoyl homoserine lactone (OHHL) and HHL were detected in Vibrio salmonicida. N-3-oxo-octanoyl homoserine...... lactone (OOHL) and N-3-octanoyl homoserine lactone (OHL) were detected in Y. ruckeii. AHLs were not detected from strains of Photobacterium damselae, Flavobacterium psychrophilum or Moritella viscosa. AHLs were extracted from fish infected with Y. ruckeri but not from fish infected with A. salmonicida...

Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles

OpenAIRE

Yana I. Pylina; Dmitry M. Shadrin; Oksana G. Shevchenko; Olga M. Startseva; Igor O. Velegzhaninov; Dmitry V. Belykh; Ilya O. Velegzhaninov

2017-01-01

In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one ...

Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area.

Science.gov (United States)

Paljetak, Hana Cipcic; Tomaskovic, Linda; Matijasic, Mario; Bukvic, Mirjana; Fajdetic, Andrea; Verbanac, Donatella; Peric, Mihaela

2017-01-01

Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chemoselective synthesis of sialic acid 1,7-lactones.

Science.gov (United States)

Allevi, Pietro; Rota, Paola; Scaringi, Raffaella; Colombo, Raffaele; Anastasia, Mario

2010-08-20

The chemoselective synthesis of the 1,7-lactones of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-d-glycero-d-galacto-nononic acid is accomplished in two steps: a simple treatment of the corresponding free sialic acid with benzyloxycarbonyl chloride and a successive hydrogenolysis of the formed 2-benzyloxycarbonyl 1,7-lactone. The instability of the 1,7-lactones to protic solvents has been also evidenced together with the rationalization of the mechanism of their formation under acylation conditions. The results permit to dispose of authentic 1,7-sialolactones to be used as reference standards and of a procedure useful for the preparation of their isotopologues to be used as inner standards in improved analytical procedures for the gas liquid chromatography-mass spectrometry (GLC-MS) analysis of 1,7-sialolactones in biological media.

Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum).

Science.gov (United States)

Xuan, T D; Elzaawely, A A; Fukuta, M; Tawata, S

2006-02-08

This is the first report showing that kava lactones are plant and plant fungus growth inhibitors. Aqueous extract of kava roots showed high allelopathic potential and strongly suppressed germination and growth of lettuce, radish, barnyardgrass, and monochoria. Nine kava lactones were detected using GC-MS including desmethoxyyagonin, kavain, 7,8-dihydrokavain, hydroxykavain, yagonin, 5,6,7,8-tetrahydroxyyagonin, methysticin, dihydromethysticin, and 11-hydroxy-12-methoxydihydrokavain. Quantities of desmethoxyyagonin, kavain, 7,8-dihydrokavain, yagonin, methysticin, and dihydromethysticin detected were 4.3, 6.9, 18.6, 5.7, 1.4, and 5.4 mg/g of dry weight, respectively. These six major lactones in kava roots showed great herbicidal and antifungal activities. Growth of lettuce and barnyardgrass were significantly inhibited at 1-10 ppm, and four plant fungi including Colletotrichum gloeosporides, Fusarium solani, Fusarium oxysporum, and Trichoderma viride were significantly inhibited at 10-50 ppm. The biological activities of kava lactones were characterized by different double-bond linkage patterns in positions 5,6 and 7,8. The findings of this study suggest that kava lactones may be useful for the development of bioactive herbicides and fungicides.

Toward understanding macrocycle specificity of iron on the dioxygen-binding ability: a theoretical study.

Science.gov (United States)

Sun, Yong; Chen, Kexian; Jia, Lu; Li, Haoran

2011-08-14

In an effort to examine the interaction between dioxygen and iron-macrocyclic complexes, and to understand how this interaction was affected by those different macrocyclic ligands, dioxygen binding with iron-porphyrin, iron-phthalocyanine, iron-dibenzotetraaza[14]annulene, and iron-salen complexes is investigated by means of quantum chemical calculations utilizing Density Functional Theory (DFT). Based on the analysis of factors influencing the corresponding dioxygen binding process, it showed that different macrocyclic ligands possess different O-O bond distances, and different electronic configurations for the bound O(2) and non-aromatic macrocyclic ligands favor dioxygen activation. Furthermore, the smaller the energy gap between the HOMO of iron-macrocyclic complexes and the LUMO of dioxygen, the more active the bound O(2) becomes, with a longer O-O bond distance and a shorter Fe-O bond length.

Pharmacological insight into the anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R.Br. ex Cass.

Science.gov (United States)

McKinnon, R; Binder, M; Zupkó, I; Afonyushkin, T; Lajter, I; Vasas, A; de Martin, R; Unger, C; Dolznig, H; Diaz, R; Frisch, R; Passreiter, C M; Krupitza, G; Hohmann, J; Kopp, B; Bochkov, V N

2014-10-15

Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

Complexes of macrocyclic dibenzo-18-crown-6 polyether with nitrates of some rare earths

International Nuclear Information System (INIS)

Gren', A.I.; Zakhariya, N.F.; Vityuk, N.V.; Kalishevich, V.S.

1984-01-01

The purpose of the investigation is to obtain and study the structure of complexes of macrocyclic polyether dibenzo-18-crown-6(D-18-C-6) with REE nitrates (Ln, Pr, Nd, Er). Synthesis has been realized by mixing the solutions 2 mol Ln(NO 3 ) 3 and 2 mmol D-18-C-6 into 30-50 ml acetonitrile and boiling during 40-60 minutes. Study on the prepared compounds by means of UV- and IR-spectroscopy proved formation of D-18-C-6 complexes with lanthanide nitrates-Ln(NO 3 ) 3 D-18-C-6. Based on studying IR-spectra a conclusion is made on deformation of D-18-C-6 structure under complexing. Distortion of the ring structure of macrocyclic polyether manifests itself in increase of CH 2 -O-CH 2 bond lengths with simultaneous reduction of four other types of bonds C 6 H 5 -O-CH 2 . Synthesized complexes are stated to have different solubility in acetonitrile which increases in the La 3 ) 3 xD-18-C-6 is noted

Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling.

Science.gov (United States)

Assem, Naila; Ferreira, David J; Wolan, Dennis W; Dawson, Philip E

2015-07-20

Macrocyclization is a broadly applied approach for overcoming the intrinsically disordered nature of linear peptides. Herein, it is shown that dichloroacetone (DCA) enhances helical secondary structures when introduced between peptide nucleophiles, such as thiols, to yield an acetone-linked bridge (ACE). Aside from stabilizing helical structures, the ketone moiety embedded in the linker can be modified with diverse molecular tags by oxime ligation. Insights into the structure of the tether were obtained through co-crystallization of a constrained S-peptide in complex with RNAse S. The scope of the acetone-linked peptides was further explored through the generation of N-terminus to side chain macrocycles and a new approach for generating fused macrocycles (bicycles). Together, these studies suggest that acetone linking is generally applicable to peptide macrocycles with a specific utility in the synthesis of stabilized helices that incorporate functional tags. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and synthesis of chalcone-based macrocyclic polyethers

Directory of Open Access Journals (Sweden)

Subrata Jana

2015-12-01

Full Text Available A series of chalcone-based macrocyclic ethers have been synthesized. These macrocyclic ethers contain polyether as well as extended conjugation to the benzene ring to function as fluorescent sensor for cations. The modeling studies show that the chalcone part of the receptors remains partially out of plane from the polyether part and the keto moiety of the receptors always directed outwardly in the receptor itself. This may be changed during the recognition of metal ions. The tendency of the fluorophore, to be out of plane, increases with increasing the ring size.

Template Syntheses, Crystal Structures and Supramolecular Assembly of Hexaaza Macrocyclic Copper(II) Complexes

International Nuclear Information System (INIS)

Kim, Taehyung; Kim, Ju Chang; Lough, Alan J.

2013-01-01

Two new hexaaza macrocyclic copper(II) complexes were prepared by a template method and structurally characterized. In the solid state, they were self-assembled by intermolecular interactions to form the corresponding supramolecules 1 and 2, respectively. In the structure of 1, the copper(II) macrocycles are bridged by a tp ligand to form a macrocyclic copper(II) dimer. The dimer extends its structure by intermolecular forces such as hydrogen bonds and C-H···π interactions, resulting in the formation of a double stranded 1D supramolecule. In 2, the basic structure is a monomeric copper(II) macrocycle with deprotonated imidazole pendants. An undulated 1D hydrogen bonded array is achieved through hydrogen bonds between imidazole pendants and secondary amines, where the imidazole pendants act as a hydrogen bond acceptor. The 1D hydrogen bonded supramolecular chain is supported by C-H···π interactions between the methyl groups of acetonitrile ligands and imidazole pendants of the copper(II) macrocycles. In both complexes, the introduction of imidazoles to the macrocycle as a pendant plays an important role for the formation of supramolecules, where they act as intermolecular hydrogen bond donors and/or acceptors, C-H···π and π-π interactions

Spectroscopic and electrochemical investigation with coordination stabilities: Mononuclear manganese(II) complexes derived from different constituents macrocyclic ligands

Science.gov (United States)

Kumar, Rajiv; Chnadra, S.; Mishra, Parashuram

2007-12-01

Since the manganese(II) complexes are known as having a high degree of stability, some of them may be able to play a very important role in biosystems. We prepared manganese(II) complexes with different chromospheres containing macrocyclic ligands bearing N, S and O like functional donor atoms in order to obtain different models of compounds. So these new manganese(II) complexes were derived from macrocyclic ligands by chelating them with metal ions. Thus, two macrocyclic ligands, L 1: 2,4-diphenyl-1,5-diaza-8,12-dioxo-6,7:13,14-dibenzocyclo tetradeca-1,4-diene[N 2O 2]ane; L 2: 2,4,9,11-tetraphenyl-6,13-dimethyl-1,5,8,12-traazacyclotertr-adeca-1,4,8,11-tetraene[N 4]ane; and two more different form first one viz.—L 3: 1,7-diaza-4-monothia-10,14-dioxo-8,9:15,16-cyclohexadecane[N 2O 2S]ane and L 4: 4,13-diaoxa-1,7,10,16-hexazacyclooctadecane[N 4O 2]ane were prepared and their capacity to retain the manganese(II) ion in solid as well as aqueous solution was determined from various physiochemical techniques viz: characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements, mass, IR, electronic, ESR spectral studies and cyclic voltammetric measurements.

Turn on macrocyclic chemosensor for Al3+ ion with facile synthesis and application in live cell imaging

Science.gov (United States)

Ezhumalai, Dhineshkumar; Mathivanan, Iyappan; Chinnadurai, Anbuselvan

2018-06-01

An effort of a new Schiff base macrocyclic chemosensor, 14‑methyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecaphane‑2,5,8,11,14,17‑hexaene (me1) and 14,74‑dimethyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecadecaphane‑2,5,8,11,14,17‑hexaene (dm2), which enables selective sensing of Al3+ in aqueous DMF were synthesized by a simplistic one-step condensation reaction of macrocyclic compounds. The probe me1 and dm2 characterized by elemental analysis, FT-IR, 1H and 13C NMR, LC-MS spectral techniques. The compounds as mentioned above subjected to FE-SEM with EDS and elemental color mapping. On addition of Al3+, the fluorescent probe me1 and dm2 induces turn-on responses in both absorption and sensing spectra by a PET mechanism. The receptor me1 and dm2 serve highly selective, sensitive and turn-on detection of Al3+. Further, they did not interfere with other cations present in biological or environmental samples. The detection limit is found to be 3 μM and 5 μM. From the view of cytotoxic activity, the ability of these compounds me1 and dm2 to inhibit the growth of KB cell lines examined. The chelating functionality of compounds me1 and dm2 examined for their inhibitory properties of KB cell, live cell images. The compounds me1 and dm2 subjected to theoretical studies by DFT-B3LYP invoking the 6-31G level of theory. The energy of the HOMO and LUMO has been established.

Characterization of E and Z isomers in macrocyclic lactones and acyclic pheromones by NMR spectra

International Nuclear Information System (INIS)

Mahajan, J.R.; Resck, I.S.; Braz Filho, R.; Carvalho, M.G. de

1995-01-01

A large proportion of pheromones, isolated from a variety of insects, constitutes a big list of diversely functionalized acyclic compounds, which have been synthesized by several routes. Catalytic or chemical methods were examined for the Z to E isomerization and their efficiency checked by 1 H and 13 C NMR spectra. Nuclear magnetic resonance has been used to identify and characterize molecular structure of the compounds, besides chemical shifts was analysed

Biodegradable poly lactone-family polymer and their applications in medical field

International Nuclear Information System (INIS)

Wang, S.; Bei, J.

2005-01-01

Poly lactone-family polymers such as poly lactide, poly glycolide and polycaprolactone are kind aliphatic polyester. Since they can degrade by hydrolysis reaction under all the ph condition and possess biocompatibility, biodegradability and other good properties, especially they included not peptide bond in their molecules, they are non-antigen and non-immunization, as well as have no-toxicity and no-stimulation. So they are interested biomaterials and very useful in medical field. However the properties of all of the homo-poly lactones can not be changed in a large range, the limited properties result in limited applications of these homo-poly lactones. Based on macromolecular design, a series of copolylactones such as poly(lactide-co-glycolide) (PLGA), poly(glycolide-co-lactide-co-caprolactone) tri- component copolymer (PGLC), tri- and multi-block poly lactide/poly(ethylene oxide) copolymer (TPLE and BPLE), as well as polycaprolactone/poly lactide/poly(ethylene oxide) copolymer (PCEL) et al were synthesized by copolymerization among various lactone monomers or lactone monomers with poly(ethylene glycol). These copolylactones have wide range of degradation life from several months to years and different mechanical properties. After plasma treatment the surface property of the copolylactones were improved further and cell affinity of the copolylactones was improved obviously. The applications of these poly lactone-family polymers in medical field for used as drug carrier in drug delivery system, and as cell scaffold in tissue engineering were discussed

Schiff base oligopyrrolic macrocycles as ligands for lanthanides and actinides

International Nuclear Information System (INIS)

Sessler, Jonathan L.; Melfi, Patricia J.; Tomat, Elisa; Callaway, Wyeth; Huggins, Michael T.; Gordon, Pamela L.; Webster Keogh, D.; Date, Richard W.; Bruce, Duncan W.; Donnio, Bertrand

2006-01-01

The coordination of f-block cations with Schiff base oligopyrrolic macrocycles is discussed. Analysis of the mesophase of a uranyl 2,5-diformylpyrrole-derived expanded porphyrin complex through temperature-dependent X-ray diffraction (XRD) methods has provided evidence for liquid-crystalline properties, and for molecular stacking into columns, arranged in a 2D hexagonal lattice. In separate studies, UV-vis spectral analysis has indicated the formation of three new f-block oligopyrrolic complexes. Addition of neptunyl ([NpO 2 ] 2+ ) or plutonyl ([PuO 2 ] 2+ ) chloride salts to the free base of a dipyrromethane-derived Schiff base macrocycle induces an immediate spectral change, namely the growth of a Q-like band at 630 nm. Such changes in the absorption spectra cause a dramatic color change from pale yellow to blue. It is postulated that oxidation of this macrocycle, stimulated by reduction of the metal center, leads to the observed spectral changes. An immediate visible and spectral change is also observed with the reaction of lutetium silylamide (Lu[N(Si(CH 3 ) 3 ) 2 ] 3 ), with a different, tetrapyrrole-containing Schiff base macrocycle. In this case, the formation of a complex with 1:1 metal-to-ligand binding stoichiometry is further supported by MALDI-TOF mass spectrometry

Schiff base oligopyrrolic macrocycles as ligands for lanthanides and actinides

Energy Technology Data Exchange (ETDEWEB)

Sessler, Jonathan L. [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States)]. E-mail: sessler@mail.utexas.edu; Melfi, Patricia J. [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Tomat, Elisa [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Callaway, Wyeth [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Huggins, Michael T. [Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, 1 University Station A5300, University of Texas at Austin, Austin, TX 78712-0165 (United States); Gordon, Pamela L. [C-Chemistry and NMT-Nuclear Materials Technology Divisions, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Webster Keogh, D. [C-Chemistry and NMT-Nuclear Materials Technology Divisions, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Date, Richard W. [Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom); Bruce, Duncan W. [Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom); Department of Chemistry, University of York, Heslington, YORK YO10 5DD (United Kingdom); Donnio, Bertrand [Institut de Physique et Chimie des Materiaux de Strasbourg (IPCMS), Groupe des Materiaux Organiques (GMO), CNRS-ULP - UMR 7504, 23 rue du Loess BP 43, F-67034 Strasbourg Cedex 2 (France)

2006-07-20

The coordination of f-block cations with Schiff base oligopyrrolic macrocycles is discussed. Analysis of the mesophase of a uranyl 2,5-diformylpyrrole-derived expanded porphyrin complex through temperature-dependent X-ray diffraction (XRD) methods has provided evidence for liquid-crystalline properties, and for molecular stacking into columns, arranged in a 2D hexagonal lattice. In separate studies, UV-vis spectral analysis has indicated the formation of three new f-block oligopyrrolic complexes. Addition of neptunyl ([NpO{sub 2}]{sup 2+}) or plutonyl ([PuO{sub 2}]{sup 2+}) chloride salts to the free base of a dipyrromethane-derived Schiff base macrocycle induces an immediate spectral change, namely the growth of a Q-like band at 630 nm. Such changes in the absorption spectra cause a dramatic color change from pale yellow to blue. It is postulated that oxidation of this macrocycle, stimulated by reduction of the metal center, leads to the observed spectral changes. An immediate visible and spectral change is also observed with the reaction of lutetium silylamide (Lu[N(Si(CH{sub 3}){sub 3}){sub 2}]{sub 3}), with a different, tetrapyrrole-containing Schiff base macrocycle. In this case, the formation of a complex with 1:1 metal-to-ligand binding stoichiometry is further supported by MALDI-TOF mass spectrometry.

Fixation of carbon dioxide by macrocyclic lanthanide(III) complexes under neutral conditions producing self-assembled trimeric carbonato-bridged compounds with μ3-η2:η2:η2 bonding.

Science.gov (United States)

Bag, Pradip; Dutta, Supriya; Biswas, Papu; Maji, Swarup Kumar; Flörke, Ulrich; Nag, Kamalaksha

2012-03-28

A series of mononuclear lanthanide(III) complexes [Ln(LH(2))(H(2)O)(3)Cl](ClO(4))(2) (Ln = La, Nd, Sm, Eu, Gd, Tb, Lu) of the tetraiminodiphenolate macrocyclic ligand (LH(2)) in 95 : 5 (v/v) methanol-water solution fix atmospheric carbon dioxide to produce the carbonato-bridged trinuclear complexes [{Ln(LH(2))(H(2)O)Cl}(3)(μ(3)-CO(3))](ClO(4))(4)·nH(2)O. Under similar conditions, the mononuclear Y(III) complex forms the dimeric compound [{Y(LH(2))(H(2)O)Cl}(μ(2)-CO(3)){Y(LH(2))(H(2)O)(2)}](ClO(4))(3)·4H(2)O. These complexes have been characterized by their IR and NMR ((1)H, (13)C) spectra. The X-ray crystal structures have been determined for the trinuclear carbonato-bridged compounds of Nd(III), Gd(III) and Tb(III) and the dinuclear compound of Y(III). In all cases, each of the metal centers are 8-coordinate involving two imine nitrogens and two phenolate oxygens of the macrocyclic ligand (LH(2)) whose two other imines are protonated and intramolecularly hydrogen-bonded with the phenolate oxygens. The oxygen atoms of the carbonate anion in the trinuclear complexes are bonded to the metal ions in tris-bidentate μ(3)-η(2):η(2):η(2) fashion, while they are in bis-bidentate μ(2)-η(2):η(2) mode in the Y(III) complex. The magnetic properties of the Gd(III) complex have been studied over the temperature range 2 to 300 K and the magnetic susceptibility data indicate a very weak antiferromagnetic exchange interaction (J = -0.042 cm(-1)) between the Gd(III) centers (S = 7/2) in the metal triangle through the carbonate bridge. The luminescence spectral behaviors of the complexes of Sm(III), Eu(III), and Tb(III) have been studied. The ligand LH(2) acts as a sensitizer for the metal ions in an acetonitrile-toluene glassy matrix (at 77 K) and luminescence intensities of the complexes decrease in the order Eu(3+) > Sm(3+) > Tb(3+).

Enhanced corrosion resistance of carbon steel in normal sulfuric acid medium by some macrocyclic polyether compounds containing a 1,3,4-thiadiazole moiety: AC impedance and computational studies

International Nuclear Information System (INIS)

Bentiss, F.; Lebrini, M.; Vezin, H.; Chai, F.; Traisnel, M.; Lagrene, M.

2009-01-01

We report here the use of macrocyclic polyether compounds containing a 1,3,4-thiadiazole moiety (n-MCTH) in the corrosion inhibition of C38 carbon steel in 0.5 M H 2 SO 4 acid medium. The aim of this work is devoted to study the inhibition characteristics of these compounds for acid corrosion of C38 steel using electrochemical impedance spectroscopy (EIS). Data obtained from EIS show a frequency distribution and therefore a modeling element with frequency dispersion behaviour, a constant phase element (CPE) has been used. The experimental results obtained revealed that these compounds inhibited the steel corrosion in acid solution and the protection efficiency increased with increasing inhibitors concentration. The difference in their inhibitive action can be explained on the basis of the number of oxygen atoms present in the polyether ring which contribute to the chemisorption strength through the donor acceptor bond between the non bonding electron pair and the vacant orbital of metal surface. Adsorption of n-MCTH was found to follow the Langmuir's adsorption isotherm. The thermodynamic functions of adsorption process were calculated and the interpretation of the results is given. These results are complemented with quantum chemical study in order to provide an explanation of the differences between the probed inhibitors. Correlation between the inhibition efficiency and the structure of these compounds are presented.

Comparison of simultaneous patch testing with parthenolide and sesquiterpene lactone mix

DEFF Research Database (Denmark)

Orion, E; Paulsen, Evy; Andersen, Klaus Ejner

1998-01-01

Several studies have pointed out that the sesquiterpene lactone (SL) mix is a safe, though inadequate, screen for Compositae allergy. To test the usefulness of the sesquiterpene lactone parthenolide as a supplementary Compositae screening test to the mix, both were included in the standard series...

m-Diethynylbenzene macrocycles: syntheses and self-association behavior in solution.

Science.gov (United States)

Tobe, Yoshito; Utsumi, Naoto; Kawabata, Kazuya; Nagano, Atsushi; Adachi, Kiyomi; Araki, Shunji; Sonoda, Motohiro; Hirose, Keiji; Naemura, Koichiro

2002-05-15

m-Diethynylbenzene macrocycles (DBMs), buta-1,3-diyne-bridged [4(n)]metacyclophanes, have been synthesized and their self-association behaviors in solution were investigated. Cyclic tetramers, hexamers, and octamers of DBMs having exo-annular octyl, hexadecyl, and 3,6,9-trioxadecyl ester groups were prepared by intermolecular oxidative coupling of dimer units or intramolecular cyclization of the corresponding open-chain oligomers. The aggregation properties were investigated by two methods, the (1)H NMR spectra and the vapor pressure osmometry (VPO). Although some discrepancies were observed between the association constants obtained from the two methods, the qualitative view was consistent with each other. The analysis of self-aggregation by VPO revealed unique aggregation behavior of DBMs in acetone and toluene, which was not elucidated by the NMR method. Namely, the association constants for infinite association are several times larger than the dimerization constant, suggesting that the aggregation is enhanced by the formation of dimers (a nucleation mechanism). In polar solvents, DBMs aggregate more strongly than in chloroform due to the solvophobic interactions between the macrocyclic framework and the solvents. Moreover, DBMs self-associate in aromatic solvents such as toluene and o-xylene more readily than in chloroform. In particular, the hexameric DBM having a large macrocyclic cavity exhibits extremely large association constants in aromatic solvents. By comparing the aggregation properties of DBMs with the corresponding acyclic oligomers, the effect of the macrocyclic structure on the aggregation propensity was clarified. Finally, it turned out that DBMs tend to aggregate more readily than the corresponding phenylacetylene macrocycles, acetylene-bridged [2(n)]metacyclophanes, owing to the withdrawal of the electron density from the aromatic rings by the butadiyne linkages which facilitates pi-pi stacking interactions.

Some aspects of the extraction separation of actinides by macrocyclic crown compounds

International Nuclear Information System (INIS)

Kumar, Anil; Singh, R.K.; Bajpai, D.D.; Shukla, J.P.

1994-01-01

Selective and effective extraction-separation of U(VI) and Pu(IV) from aqueous nitric acid media by several crown ethers have been investigated in detail. The critical study of various parameters namely aqueous phase acidity, reagent concentration, diluent, period of equilibration, aqueous to organic phase ratio, strippant and diverse ions, have established the conditions for their optimum extraction. Influence of the introduction of sulfur into a crown ether ring forming a mixed sulfur-oxygen containing macrohetrocycle for improved extraction of actinides is also studied. The species extracted appear to be of ion-pair type, UO 2 (CE) 2+ .2NO 3- and Pu(CE) 2 4+ .4NO 3- formed with U(VI) and Pu(IV), respectively. The apparent extraction equilibrium constant, log Kex, into toluene by DC18C6 with U(VI) is 0.44 and 4.44 for Pu(IV). Recovery of actinides from loaded macrocycles is easily accomplished using dilute oxalic acid, perchloric acid, sulphuric acid or sodium carbonate as the strippants. The lack of interference from even appreciable amounts of possible fission product contaminants is a notable feature of this separation procedure. (author). 20 refs., 6 figs., 6 tabs

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

Directory of Open Access Journals (Sweden)

Helena M. C. Ferraz

2008-01-01

Full Text Available The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

Macrocyclic ligands for uranium complexation. Final report, August 1, 1986--March 31, 1993

International Nuclear Information System (INIS)

Potts, K.T.

1993-01-01

Macrocycles, designed for complexation of the uranyl ion by computer modeling studies and utilizing six ligating atoms in the equatorial plane of the uranyl ions, have been prepared and their complexation of the uranyl ions evaluated. The ligating atoms, either oxygen or sulfur, were part of acylurea, biuret or thiobiuret subunits with alkane chains or pyridine units completing the macrocyclic periphery. These macrocycles with only partial preorganization formed uranyl complexes in solution but no crystalline complexes were isolated. Refinement of the cavity diameter by variation of the peripheral functional groups is currently studied to achieve an optimized cavity diameter of 4.7--5.2 angstrom. Acyclic ligands containing the same ligating atoms in equivalent functional entities were found to form a crystalline 1:1 uranyl-ligand complex (stability constant log K = 10.7) whose structure was established by X-ray data. This complex underwent a facile, DMSO-induced rearrangement to a 2:1 uranyl-ligand complex whose structure was also established by X-ray data. The intermediates to the macrocycles all behaved as excellent ligands for the complexation of transition metals. Acylthiourea complexes of copper and nickel as well as intermolecular, binuclear copper and nickel complexes of bidentate carbonyl thioureas formed readily and their structures were established in several representative instances by X-ray structural determinations. Tetradentate bis(carbonylthioureas) were found to be very efficient selective reagents for the complexation of copper in the presence of nickel ions. Several preorganized macrocycles were also prepared but in most instances these macrocycles underwent ring-opening under complexation conditions

A new family of NxOy pyridine-containing macrocycles: synthesis and characterization of their Y(III), Ln(III), Zn(II), and Cd(II) coordination compounds

International Nuclear Information System (INIS)

Lodeiro, C.; Bastida, R.; Bertolo, E.; Rodriguez, A.

2004-01-01

Reaction between 2,6-bis(2-formylphenoxymethyl)pyridine and N,N-bis(3-aminopropyl)methylamine or tris(2-aminoethyl)amine has been used as the starting point for the synthesis of seven oxa-aza macrocyclic ligands, five of them never reported previously. They all feature different pendant arms, which provide a wide range of coordination possibilities. The Schiff base macrocycles L 1 and L 4 and their reduced ligands L 2 and L 5 are derived from 2,6-bis(2-formylphenoxymethyl)pyridine and tris(2-aminoethyl)amine or N,N-bis(3-aminopropyl)methylamine, respectively. The reaction of L 1 with salicylaldehyde forms L 3 , which features an imine bond in the pendant arm. The ligand L 5 has been the precursor for the pendant-armed L 6 and L 7 , by alkylation of the free NH groups with methyl-imidazole or methyl-indole. By a template or a nontemplate approach, we have synthesized different mono- and dinuclear complexes with Y(III), Ln(III), Zn(II), and Cd(II) cations. Both the free macrocyclic ligands and their corresponding metal complexes have been characterized by microanalysis, IR, UV-vis, 1 H and 13 C NMR spectroscopy, FAB mass spectrometry, MS electrospray, and conductivity measurements. (author)

Study of water role during the complexing of uranyl aquanitrate compounds with cyclic polyethers

International Nuclear Information System (INIS)

Belomestnykh, V.I.; Sveshnikova, L.B.; Shabel'nik, K.S.

1990-01-01

By the method of vibrational spectroscopy and thermogravimetry the determining role of water molecules during complexing of uranyl aquonitrate compounds with macrocyclic polyethers is confirmed. It is ascertained that in the synthesized complexes of the composition UO 2 (NO 3 ) 2 (H 2 O) 2 ·mH 2 O·nL (m=0,1,2; L-18-crown-6, 15-crown-5, dibenzo-18-crown-6; n=1,2) molecules of macrocyclic ligand are joined at the expense of strong hydrogen bonds with participation of protons of crystallographically nonequivalent water molecules. In the compounds hydrogen bonds of water-water and water-nitrato group type are also realized. Energies of the above-mentioned bonds are calculated

Sesquiterpene lactones from Taraxacum obovatum.

Science.gov (United States)

Michalska, Klaudia; Kisiel, Wanda

2003-02-01

Two new guaianolide glucosides, deacetylmatricarin 8-O-beta-glucopyranoside and 11beta-hydroxyleukodin 11-O-beta-glucopyranoside, were isolated from roots of Taraxacum obovatum, along with four known sesquiterpene lactones, deacetylmatricarin, sonchuside A, taraxinic acid beta-glucopyranosyl ester and its 11beta,13-dihydro derivative. Their structures were established by spectral methods.

Homoserine Lactone as a Structural Key Element for the Synthesis of Multifunctional Polymers

Directory of Open Access Journals (Sweden)

Fabian Marquardt

2017-04-01

Full Text Available The use of bio-based building blocks for polymer synthesis represents a milestone on the way to “green” materials. In this work, two synthetic strategies for the preparation of multifunctional polymers are presented in which the key element is the functionality of homoserine lactone. First, the synthesis of a bis cyclic coupler based on a thiolactone and homoserine lactone is displayed. This coupler was evaluated regarding its regioselectivity upon reaction with amines and used in the preparation of multifunctional polymeric building blocks by reaction with diamines. Furthermore, a linear polyglycidol was functionalized with homoserine lactone. The resulting polyethers with lactone groups in the side chain were converted to cationic polymers by reaction with 3-(dimethylamino-1-propylamine followed by quaternization with methyl iodide.

Chlorine-containing natural compounds in higher plants

DEFF Research Database (Denmark)

Engvild, Kjeld Christensen

1986-01-01

More than 130 chlorine-containing compounds have been isolated from higher plants and ferns; about half are polyacetylenes, thiophenes and sesquiterpene lactones from the Asteraceae. A chlorinated chlorophyll may be an important part of photosystem 1. High biological activity is found in 4...

The Synthesis, Structures and Chemical Properties of Macrocyclic Ligands Covalently Bonded into Layered Arrays

International Nuclear Information System (INIS)

Clearfield, Abraham

2003-01-01

OAK-B135 The immobilization of crown ethers tends to limit the leveling effect of solvents making the macrocycles more selective. In addition immobilization has the added advantage of relative ease of recovery of the otherwise soluble crown. We have affixed CH2PO3H2 groups to azacrown ethers. The resultant phosphorylated macrocycles may spontaneously aggregate into crystalline supramolecular linear arrays or contacted with cations produce layered or linear polymers. In the linear polymers the metal and phosphonic acids covalently bond into a central stem with the macrocyclic rings protruding from the stem as leaves on a twig. Two types of layered compounds were obtained with group 4 metals. Monoaza-crown ethers form a bilayer where the M4+ plus phosphonic acid groups build the layer and the rings fill the interlayer space. 1, 10-diazadiphosphonic acids cross-link the metal phosphonate layers forming a three-dimensional array of crown ethers. In order to improve diffusion into these 3-D arrays they are spaced by inclusion of phosphate or phosphate groups. Two series of azamacrocylic crown ethers were prepared containing rings with 20 to 32 atoms. These larger rings can complex two cations per ring. Methylene phosphonic acid groups have been bonded to the aza ring atoms to increase the complexing ability of these ligands. Our approach is to carry out acid-base titrations in the absence and presence of cations to determine the pKa values of the protons, both those bonded to aza groups and those associated with the phosphonic acid groups. From the differences in the titration curves obtained with and without the cations present we obtain the stoichiometry of complex formation and the complex stability constants. Some of the applications we are targeting include phase transfer catalysis, separation of cations and the separation of radioisotopes for diagnostic and cancer therapeutic purposes

Minireview: Mode of action of meta-diamide insecticides.

Science.gov (United States)

Nakao, Toshifumi; Banba, Shinichi

2015-06-01

Meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor noncompetitive antagonists showing high insecticidal activity against Spodoptera litura. The mode of action of the meta-diamides was demonstrated to be distinct from that of conventional noncompetitive antagonists (NCAs) such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. It was suggested that meta-diamides act at or near G336 in the M3 region of the Drosophila RDL GABA receptor. Although the site of action of the meta-diamides appears to overlap with that of macrocyclic lactones including avermectins and milbemycins, differential effects of mutations on the actions of the meta-diamides and the macrocyclic lactones were observed. Molecular modeling studies revealed that the meta-diamides may bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor better when in the closed state, which is distinct from the NCA-binding site, which is in a channel formed by M2s. In contrast, the macrocyclic lactones were suggested to bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor when in the open state. Furthermore, mechanisms underlying the high selectivity of meta-diamides are discussed. This minireview highlights the unique features of novel meta-diamide insecticides and demonstrates why meta-diamides are anticipated to become prominent insecticides that are effective against pests resistant to cyclodienes and fipronil. Copyright © 2014 Elsevier Inc. All rights reserved.

Adaptive self-assembly and induced-fit transformations of anion-binding metal-organic macrocycles

Science.gov (United States)

Zhang, Ting; Zhou, Li-Peng; Guo, Xiao-Qing; Cai, Li-Xuan; Sun, Qing-Fu

2017-06-01

Container-molecules are attractive to chemists due to their unique structural characteristics comparable to enzymes and receptors in nature. We report here a family of artificial self-assembled macrocyclic containers that feature induced-fit transformations in response to different anionic guests. Five metal-organic macrocycles with empirical formula of MnL2n (M=Metal L=Ligand n=3, 4, 5, 6, 7) are selectively obtained starting from one simple benzimidazole-based ligand and square-planar palladium(II) ions, either by direct anion-adaptive self-assembly or induced-fit transformations. Hydrogen-bonding interactions between the inner surface of the macrocycles and the anionic guests dictate the shape and size of the product. A comprehensive induced-fit transformation map across all the MnL2n species is drawn, with a representative reconstitution process from Pd7L14 to Pd3L6 traced in detail, revealing a gradual ring-shrinking mechanism. We envisage that these macrocyclic molecules with adjustable well-defined hydrogen-bonding pockets will find wide applications in molecular sensing or catalysis.

High yielding synthesis of 2,2′-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes

OpenAIRE

Lewis, J. E. M.; Bordoli, R. J.; Denis, M.; Fletcher, C. J.; Galli, M.; Neal, E. A.; Rochette, E. M.; Goldup, S. M.

2016-01-01

We present an operationally simple approach to 2,2?-bipyridine macrocycles. Our method uses simple starting materials to produce these previously hard to access rotaxane precursors in remarkable yields (typically >65%) across a range of scales (0.1–5 mmol). All of the macrocycles reported are efficiently converted (>90%) to rotaxanes under AT-CuAAC conditions. With the requisite macrocycles finally available in sufficient quantities, we further demonstrate their long term utility throug...

Covalent lanthanide(III) macrocyclic complexes: the bonding nature and optical properties of a promising single antenna molecule.

Science.gov (United States)

Rabanal-León, Walter A; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro

2014-12-21

The present work is focused on the elucidation of the electronic structure, bonding nature and optical properties of a series of low symmetry (C2) coordination compounds of type [Ln(III)HAM](3+), where "Ln(III)" are the trivalent lanthanide ions: La(3+), Ce(3+), Eu(3+) and Lu(3+), while "HAM" is the neutral six-nitrogen donor macrocyclic ligand [C22N6H26]. This systematic study has been performed in the framework of the Relativistic Density Functional Theory (R-DFT) and also using a multi-reference approach via the Complete Active Space (CAS) wavefunction treatment with the aim of analyzing their ground state and excited state electronic structures as well as electronic correlation. Furthermore, the use of the energy decomposition scheme proposed by Morokuma-Ziegler and the electron localization function (ELF) allows us to characterize the bonding between the lanthanide ions and the macrocyclic ligand, obtaining as a result a dative-covalent interaction. Due to a great deal of lanthanide optical properties and their technological applications, the absorption spectra of this set of coordination compounds were calculated using the time-dependent density functional theory (TD-DFT), where the presence of the intense Ligand to Metal Charge Transfer (LMCT) bands in the ultraviolet and visible region and the inherent f-f electronic transitions in the Near-Infra Red (NIR) region for some lanthanide ions allow us to propose these systems as "single antenna molecules" with potential applications in NIR technologies.

Selective CO2 gas adsorption in the narrow crystalline cavities of flexible peptide metallo-macrocycles.

Science.gov (United States)

Miyake, Ryosuke; Kuwata, Chika; Masumoto, Yui

2015-02-21

Crystalline peptide Ni(ii)-macrocycles (BF4(-) salt) exhibited moderate CO2 gas adsorption (ca. 6-7 CO2 molecules per macrocycle) into very narrow cavities (narrowest part gas in preference to CH4 and N2 gases.

Ketopantoyl-lactone reductase from Candida parapsilosis: purification and characterization as a conjugated polyketone reductase.

Science.gov (United States)

Hata, H; Shimizu, S; Hattori, S; Yamada, H

1989-02-24

Ketopantoyl-lactone reductase (2-dehydropantoyl-lactone reductase, EC 1.1.1.168) was purified and crystallized from cells of Candida parapsilosis IFO 0708. The enzyme was found to be homogeneous on ultracentrifugation, high-performance gel-permeation liquid chromatography and SDS-polyacrylamide gel electrophoresis. The relative molecular mass of the native and SDS-treated enzyme is approximately 40,000. The isoelectric point of the enzyme is 6.3. The enzyme was found to catalyze specifically the reduction of a variety of natural and unnatural polyketones and quinones other than ketopantoyl lactone in the presence of NADPH. Isatin and 5-methylisatin are rapidly reduced by the enzyme, the Km and Vmax values for isatin being 14 microM and 306 mumol/min per mg protein, respectively. Ketopantoyl lactone is also a good substrate (Km = 333 microM and Vmax = 481 mumol/min per mg protein). Reverse reaction was not detected with pantoyl lactone and NADP+. The enzyme is inhibited by quercetin, several polyketones and SH-reagents. 3,4-Dihydroxy-3-cyclobutene-1,2-dione, cyclohexenediol-1,2,3,4-tetraone and parabanic acid are uncompetitive inhibitors for the enzyme, the Ki values being 1.4, 0.2 and 3140 microM, respectively, with isatin as substrate. Comparison of the enzyme with the conjugated polyketone reductase of Mucor ambiguus (S. Shimizu, H. Hattori, H. Hata and H. Yamada (1988) Eur. J. Biochem. 174, 37-44) and ketopantoyl-lactone reductase of Saccharomyces cerevisiae suggested that ketopantoyl-lactone reductase is a kind of conjugated polyketone reductase.

Concise Synthesis of Macrocycles by Multicomponent Reactions

NARCIS (Netherlands)

Abdelraheem, Eman M. M.; Khaksar, Samad; Dömling, Alexander

2018-01-01

A short reaction pathway was devised to synthesize a library of artificial 18-27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure

Towards the industrialization of new biosurfactants: Biotechnological opportunities for the lactone esterase gene from Starmerella bombicola.

Science.gov (United States)

Roelants, Sophie L K W; Ciesielska, Katarzyna; De Maeseneire, Sofie L; Moens, Helena; Everaert, Bernd; Verweire, Stijn; Denon, Quenten; Vanlerberghe, Brecht; Van Bogaert, Inge N A; Van der Meeren, Paul; Devreese, Bart; Soetaert, Wim

2016-03-01

Although sophorolipids (SLs) produced by S. bombicola are a real showcase for the industrialization of microbial biosurfactants, some important drawbacks are associated with this efficient biological process, e.g., the simultaneous production of acidic and lactonic SLs. Depending on the application, there is a requirement for the naturally produced mixture to be manipulated to give defined ratios of the components. Recently, the enzyme responsible for the lactonization of SLs was discovered. The discovery of the gene encoding this lactone esterase (sble) enabled the development of promising S. bombicola strains producing either solely lactonic (using a sble overexpression strain described in this paper: oe sble) or solely acidic SLs (using a sble deletion strain, which was recently described, but not characterized yet: Δsble). The new S. bombicola strains were used to investigate the production processes (fermentation and purification) of either lactonic or acidic SLs. The strains maintain the high inherent productivities of the wild-type or even perform slightly better and thus represent a realistic industrial opportunity. 100% acidic SLs with a mixed acetylation pattern were obtained for the Δsble strain, while the inherent capacity to selectively produce lactonic SLs was significantly increased (+42%) for the oe sble strain (99% lactonic SLs). Moreover, the regulatory effect of citrate on lactone SL formation for the wild-type was absent in this new strain, which indicates that it is more robust and better suited for the industrial production of lactonic SLs. Basic parameters were determined for the purified SLs, which confirm that the two new strains produce molecules with distinctive properties of which the application potential can now easily be investigated independently. © 2015 Wiley Periodicals, Inc.

3-Epiabruslactone A, a New Triterpene Lactone Isolated from Austroplenckia populnea

Directory of Open Access Journals (Sweden)

Silva Grácia Divina de Fátima

1998-01-01

Full Text Available A new lactonic triterpene isolated from the heartwood of Austroplenckia populnea (Celastraceae was characterized as 3alpha-hydroxyolean-12-en-29,22alpha-olide (the gamma-lactone of the 3alpha,22alpha-dihydroxyolean-12-en-29alpha-oic acid, the 3-epimer of the abruslactone A, on the basis of its spectral data, chemical transformations, and single crystal X-ray analysis.

Synthesis and Characterization of Macrocyclic Polyether N,N'-Diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6.

Science.gov (United States)

Toeri, Julius; Laborie, Marie-Pierre

2016-01-29

In this study an efficient and direct production procedure for a macrocyclic polyether N,N'-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethyl)prop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium hydroxide to enhance the cyclization process, and at the end of the reaction, the reaction mixture is neutralized and the solvent replaced with water in-situ through distillation to afford a relatively pure precipitate that is easily recrystallized from acetone. The yield of the macrocycle was 36%-45% and could be scaled-up to one-mole quantities. The structure and purity of this compound was verified on the basis of elemental analysis, IR, UV-Vis, ¹H-, (13)C-NMR, 2D-NMR, mass spectroscopy, and thermal analysis. The white crystalline compound has a sharp melting point of 124 °C and a crystallization temperature of 81.4 °C determined by differential scanning calorimetry. Our motivation behind the synthesis of the bibracchial lariat azacrown polyether ligand was to examine its possible applications in ion-selective polymer-supported materials.

Synthesis and Characterization of Macrocyclic Polyether N,N′-Diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6

Directory of Open Access Journals (Sweden)

Julius Toeri

2016-01-01

Full Text Available In this study an efficient and direct production procedure for a macrocyclic polyether N,N′-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethylprop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium hydroxide to enhance the cyclization process, and at the end of the reaction, the reaction mixture is neutralized and the solvent replaced with water in-situ through distillation to afford a relatively pure precipitate that is easily recrystallized from acetone. The yield of the macrocycle was 36%–45% and could be scaled-up to one-mole quantities. The structure and purity of this compound was verified on the basis of elemental analysis, IR, UV-Vis, 1H-, 13C-NMR, 2D-NMR, mass spectroscopy, and thermal analysis. The white crystalline compound has a sharp melting point of 124 °C and a crystallization temperature of 81.4 °C determined by differential scanning calorimetry. Our motivation behind the synthesis of the bibracchial lariat azacrown polyether ligand was to examine its possible applications in ion-selective polymer-supported materials.

Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours

Energy Technology Data Exchange (ETDEWEB)

Good, Stephan; Wang, Xuejuan; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Walter, Martin A.; Mueller-Brand, Jan [University Hospital, Institute of Nuclear Medicine, Basel (Switzerland); Waser, Beatrice; Reubi, Jean-Claude [University of Berne, Department of Pathology, Bern (Switzerland); Behe, Martin P. [Philipps-University of Marburg, Department of Nuclear Medicine, Marburg (Germany)

2008-10-15

Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available {beta}-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using {sup 111}In-labelled derivatives. Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using {sup 111}In as surrogate for therapeutic radiometals for in vitro and in vivo studies. Gastrin receptor affinities of the {sup nat}In-metallated compounds were determined by receptor autoradiography using {sup 125}I-CCK as radioligand. Internalisation was evaluated in AR4-2J cells. Enzymatic stability was determined by incubating the {sup 111}In-labelled peptides in human serum. Biodistribution was performed in AR4-2J-bearing Lewis rats. IC{sub 50} values of the {sup nat}In-metallated gastrin derivatives vary between 1.2 and 4.8 nmol/L for all methionine-containing derivatives. Replacement of methionine by norleucine, isoleucine, methionine-sulfoxide and methionine-sulfone resulted in significant decrease of receptor affinity (IC{sub 50} between 9.9 and 1,195 nmol/L). All cholecystokinin receptor affinities were >100 nmol/L. All {sup 111}In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All {sup 111}In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to {sup 111}In-DTPA-minigastrin 0(0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in

Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours

International Nuclear Information System (INIS)

Good, Stephan; Wang, Xuejuan; Maecke, Helmut R.; Walter, Martin A.; Mueller-Brand, Jan; Waser, Beatrice; Reubi, Jean-Claude; Behe, Martin P.

2008-01-01

Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available β-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using 111 In-labelled derivatives. Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using 111 In as surrogate for therapeutic radiometals for in vitro and in vivo studies. Gastrin receptor affinities of the nat In-metallated compounds were determined by receptor autoradiography using 125 I-CCK as radioligand. Internalisation was evaluated in AR4-2J cells. Enzymatic stability was determined by incubating the 111 In-labelled peptides in human serum. Biodistribution was performed in AR4-2J-bearing Lewis rats. IC 50 values of the nat In-metallated gastrin derivatives vary between 1.2 and 4.8 nmol/L for all methionine-containing derivatives. Replacement of methionine by norleucine, isoleucine, methionine-sulfoxide and methionine-sulfone resulted in significant decrease of receptor affinity (IC 50 between 9.9 and 1,195 nmol/L). All cholecystokinin receptor affinities were >100 nmol/L. All 111 In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All 111 In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to 111 In-DTPA-minigastrin 0(0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in lower metabolic stability. The properties of the macrocyclic

The formation of fat-derived flavour compounds during the ripening of Gouda-type cheese

NARCIS (Netherlands)

Alewijn, M.

2006-01-01

Cheese flavour is an important quality attribute, and is mainly formed during cheese ripening. Besides compounds that are formed from protein and carbohydrates, milk fat-derived compounds are essential for cheese flavour. Before, but mainly during ripening, free fatty acids, lactones, ketones,

Variability of sesquiterpene lactones in Neurolaena lobata of different origin.

Science.gov (United States)

Passreiter, C M; Aldana, B E

1998-06-01

Leaves of Neurolaena lobata (L.) R. Br. originating from Guatemala, were analyzed using HPLC for their qualitative and quantitative sesquiterpene lactone contents. Significant differences in the individual amounts of neurolenins and furanoheliangolides were found between four natural populations. When plants were cultivated on proving fields at two different localities in Guatemala, their sesquiterpene lactone patterns matched the natural population, but differed quantitatively. The meaning of these differences for the use of N. lobata in traditional medicine and its cultivation is discussed.

Stereoselective synthesis of highly substituted bicyclic γ-lactones using homoaldol addition of 1-(1-cycloalkenyl)methyl carbamates

DEFF Research Database (Denmark)

Özlügedik, M.; Kristensen, Jesper Langgaard; Reuber, J.

2004-01-01

Stereoselective addition of aldehydes 4 to metallated 1-(1-cycloalkenyl) methyl N,N-diisopropylcarbamates 1 gave cyclic homoaldol adducts 6. By applying the (-)-sparteine method, enantiomerically enriched products were obtained. These were oxidatively cyclized to diastereomerically pure ¿-lactones...... 8 via the ¿-lactol ethers 7. After deprotonation of ¿-lactones 8 with lithium hexamethyldisilazide, a further substitution was achieved. By trapping the lactone enolates 11 with ß-naphthylmethyl bromide, single diastereomers of ¿-lactones 12 were produced....

Detecting and characterizing N-acyl-homoserine lactone signal molecules by thin-layer chromatography

Science.gov (United States)

Shaw, Paul D.; Ping, Gao; Daly, Sean L.; Cha, Chung; Cronan, John E.; Rinehart, Kenneth L.; Farrand, Stephen K.

1997-01-01

Many Gram-negative bacteria regulate gene expression in response to their population size by sensing the level of acyl-homoserine lactone signal molecules which they produce and liberate to the environment. We have developed an assay for these signals that couples separation by thin-layer chromatography with detection using Agrobacterium tumefaciens harboring lacZ fused to a gene that is regulated by autoinduction. With the exception of N-butanoyl-l-homoserine lactone, the reporter detected acyl-homoserine lactones with 3-oxo-, 3-hydroxy-, and 3-unsubstituted side chains of all lengths tested. The intensity of the response was proportional to the amount of the signal molecule chromatographed. Each of the 3-oxo- and the 3-unsubstituted derivatives migrated with a unique mobility. Using the assay, we showed that some bacteria produce as many as five detectable signal molecules. Structures could be assigned tentatively on the basis of mobility and spot shape. The dominant species produced by Pseudomonas syringae pv. tabaci chromatographed with the properties of N-(3-oxohexanoyl)-l-homoserine lactone, a structure that was confirmed by mass spectrometry. An isolate of Pseudomonas fluorescens produced five detectable species, three of which had novel chromatographic properties. These were identified as the 3-hydroxy- forms of N-hexanoyl-, N-octanoyl-, and N-decanoyl-l-homoserine lactone. The assay can be used to screen cultures of bacteria for acyl-homoserine lactones, for quantifying the amounts of these molecules produced, and as an analytical and preparative aid in determining the structures of these signal molecules. PMID:9177164

Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.

Science.gov (United States)

Sowden, Rebecca J; Trotter, Katherine D; Dunbar, Lynsey; Craig, Gemma; Erdemli, Omer; Spickett, Corinne M; Reglinski, John

2013-02-01

A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

Rapid synthesis of macrocycles from diol precursors

DEFF Research Database (Denmark)

Wingstrand, Magnus; Madsen, Charlotte Marie; Clausen, Mads Hartvig

2009-01-01

A method for the formation of synthetic macrocycles with different ring sizes from diols is presented. Reacting a simple diol precursor with electrophilic reagents leads to a cyclic carbonate, sulfite or phosphate in a single step in 25-60% yield. Converting the cyclization precursor to a bis-ele...

Comparative pharmacology of flatworm and roundworm glutamate-gated chloride channels

DEFF Research Database (Denmark)

Lynagh, Timothy; Cromer, Brett A.; Dufour, Vanessa

2014-01-01

Pharmacological targeting of glutamate-gated chloride channels (GluCls) is a potent anthelmintic strategy, evidenced by macrocyclic lactones that eliminate numerous roundworm infections by activating roundworm GluCls. Given the recent identification of flatworm GluCls and the urgent need for drugs...

A randomised comparison of novolimus-eluting and zotarolimus-eluting coronary stents: 9-Month follow-up results of the EXCELLA II study

NARCIS (Netherlands)

P.W.J.C. Serruys (Patrick); S.A. Garg (Scot); A.C. Abizaid (Alexandre); J.A. Ormiston (John); S.W. Windecker (Stephan); S. Verheye (Stefan); C. Dubois (Christophe); J. Stewart (J.); K. Hauptmann (Karl); J. Schofer (Joachim); K. Stangl (Karl); B. Witzenbichler (Bernhard); M. Wiemer (Marcus); E. Barbato (Emanuele); T. de Vries (Ton); A.-M. den Drijver (Anne-Marie); H. Otake (Hiromasa); L. Meredith (Lynn); S. Toyloy (Sara); P.J. Fitzgerald (Peter)

2010-01-01

textabstractAims: Novolimus, a macrocyclic lactone with anti-proliferative properties, has a similar efficacy to currently available agents; however it requires a lower dose, and less polymer, and is therefore conceivably safer. Methods and results: The EXCELLA II study was a prospective,

N-acyl-homoserine lactone-mediated quorum-sensing in Azospirillum: an exception rather than a rule.

Science.gov (United States)

Vial, Ludovic; Cuny, Caroline; Gluchoff-Fiasson, Katia; Comte, Gilles; Oger, Phil M; Faure, Denis; Dessaux, Yves; Bally, René; Wisniewski-Dyé, Florence

2006-11-01

Forty Azospirillum strains were tested for their ability to synthesize N-acyl-homoserine lactones (AHLs). AHL production was detected for four strains belonging to the lipoferum species and isolated from a rice rhizosphere. AHL molecules were structurally identified for two strains: Azospirillum lipoferum TVV3 produces 3O,C(8)-HSL (N-3-oxo-octanoyl-homoserine-lactone), C(8)-HSL (N-3-octanoyl-homoserine-lactone), 3O,C(10)-HSL (N-3-oxo-decanoyl-homoserine-lactone), 3OH,C(10)-HSL (N-3-hydroxy-decanoyl-homoserine-lactone) and C(10)-HSL (N-3-decanoyl-homoserine-lactone), whereas A. lipoferum B518 produced 3O,C(6)-HSL (N-3-oxo-hexanoyl-homoserine-lactone), C(6)-HSL (N-3-hexanoyl-homoserine-lactone), 3O,C(8)-HSL, 3OH,C(8)-HSL and C(8)-HSL. Genes involved in AHL production were characterized for A. lipoferum TVV3 by generating a genomic library and complementing an AHL-deficient strain with sensor capabilities. Those genes, designated alpI and alpR, were found to belong to the luxI and luxR families, respectively. When cloned in a suitable heterologous host, alpI and alpR could direct the synthesis of the five cognate AHLs present in A. lipoferum TVV3. These two adjacent genes were found to be located on a 85 kb plasmid. Southern hybridization experiments with probes alpI/R indicated that genes involved in AHL production in the three other AHL-producing strains were not closely related to alpI and alpR. This study demonstrates that AHL-based quorum-sensing is not widespread among the genus Azospirillum and could be found only in some A. lipoferum strains.

A review on the effect of macrocyclic lactones on dung-dwelling insects: Toxicity of macrocyclic lactones to dung beetles

Directory of Open Access Journals (Sweden)

Carmen T. Jacobs

2015-04-01

Full Text Available Avermectins and milbemycins are commonly used in agro-ecosystems for the control of parasites in domestic livestock. As integral members of agro-ecosystems with importance in maintaining pasture health through dung burial behaviour, dung beetles are an excellent nontarget bio-indicator taxon for examining potential detrimental effects of pesticide application. The current review focuses on the relative toxicity of four different anthelmintics (ivermectin, eprinomectin, doramectin and moxidectin in dung residues using dung beetles as a bioindicator species. One of the implications of this review is that there could be an effect that extends to the entire natural assemblage of insects inhabiting and feeding on the dung of cattle treated with avermectin or milbemycin products. Over time, reduced reproductive rate would result in decreased dung beetle populations and ultimately, a decrease in the rate of dung degradation and dung burial.

C-84 Selective Porphyrin Macrocycle with an Adaptable Cavity Constructed Through Alkyne Metathesis

Energy Technology Data Exchange (ETDEWEB)

Zhang, C. X.; Long, H.; Zhang, W.

2012-06-21

A bisporphyrin macrocycle was constructed from a porphyrin-based diyne monomer in one step through alkyne metathesis. The fullerene binding studies (C{sub 60}, C{sub 70} and C{sub 84}) showed the highest binding affinity of the macrocycle for C{sub 84}, which is in great contrast to its bisporphyrin four-armed cage analogue that showed the strongest binding with C{sub 70}.

Profiling of acylated homoserine lactones of Vibrio anguillarum in vitro and in vivo: influence of growth conditions and serotype

DEFF Research Database (Denmark)

Buchholtz, Chrstiane; Nielsen, Kristian Fog; L. Milton, Debra

2006-01-01

Vibrio anguillarum produces several interlinked acylated homoserine lactone (AHL) signal molecules which may Vibrio anguillarum produces several interlinked acylated homoserine lactone (AHL) signal molecules which may influence expression of its virulence factors such as exoprotease production...... concentration) has little influence on the AHL-profile. Most strains produced N-(3-oxodecanoyl)-l-homoserine lactone (3-oxo-C10-HSL) and N-(3-hydroxy-hexanoyl)-l-homoserine lactone (3-hydroxy-C6-HSL) as the dominant molecules. Also, two spots with AHL activity appeared on TLC plates, which could...... not be identified as AHL structures. Trace amounts of N-(3-hydroxy-octanoyl)-l-homoserine lactone, N-(3-hydroxy-decanoyl)-l-homoserine lactone and N-(3-hydroxy-dodecanoyl)-l-homoserine lactone (3-hydroxy-C8-HSL, 3-hydroxy-C10-HSL and 3-oxo-C12-HSL, respectively) were also detected by HPLC-HRMS analysis from...

Zn2+ -Ion Sensing by Fluorescent Schiff Base Calix[4]arene Macrocycles.

Science.gov (United States)

Ullmann, Steve; Schnorr, René; Handke, Marcel; Laube, Christian; Abel, Bernd; Matysik, Jörg; Findeisen, Matthias; Rüger, Robert; Heine, Thomas; Kersting, Berthold

2017-03-17

A macrocyclic ligand (H 2 L) containing two o,o'-bis(iminomethyl)phenol and two calix[4]arene head units has been synthesized and its coordination chemistry towards divalent Ni and Zn investigated. The new macrocycle forms complexes of composition [ML] (M=Zn, M=Ni) and [ZnL(py) 2 ], which were characterized by elemental analysis; IR, UV/Vis, and NMR spectroscopy; electrospray ionization mass spectrometry (ESI-MS); and X-ray crystallography (for [ZnL(py) 2 ] and [NiL]). H 2 L allows the sensitive optical detection of Zn 2+ among a series of biologically relevant metal ions by a dual fluorescence enhancement/quenching effect in solution. The fluorescence intensity of the macrocycle increases by a factor of ten in the presence of Zn 2+ with a detection limit in the lower nanomolar region. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enthalpies of combustion and formation of {alpha}-D-glucoheptono-1,4-lactone and {alpha},{beta}-glucooctanoic-1,4-lactone

Energy Technology Data Exchange (ETDEWEB)

Amador, Patricia [Facultad de Ciencias Qui' micas, Benemerita Universidad Autonoma de Puebla, 14 Sur y Av. San Claudio, Col. Manuel, C.P. 72570 Puebla Pue (Mexico)], E-mail: cs000721@siu.buap.mx; Mata, Marian Y.; Flores, Henoc [Facultad de Ciencias Qui' micas, Benemerita Universidad Autonoma de Puebla, 14 Sur y Av. San Claudio, Col. Manuel, C.P. 72570 Puebla Pue (Mexico)

2008-05-15

The standard molar energies of combustion, {delta}{sub c}U{sub m}{sup 0}(cr,298.15K), of {alpha}-D-glucoheptono-1,4-lactone (GH) and {alpha},{beta}-glucooctanoic-1,4-lactone (GO) were obtained by micro-combustion calorimetry. The obtained values are -(2924.6 {+-} 2.3) kJ . mol{sup -1} and -(3459.5 {+-} 2.5) kJ . mol{sup -1}, respectively. From combustion energies, the standard molar enthalpies of formation in crystalline phase, {delta}{sub f}H{sub m}{sup 0}(cr,298.15K), for GH and GO were determined as -(1546.2 {+-} 2.5) kJ . mol{sup -1} and -(1690.6 {+-} 2.7) kJ . mol{sup -1}, respectively. Also it was found that when the hydroxyl group number increases in the aldonolactones their standard molar enthalpies of formation increase too.

Systemic allergic dermatitis caused by sesquiterpene lactones

DEFF Research Database (Denmark)

Paulsen, Evy

2017-01-01

Patients with Compositae sensitization are routinely warned against the ingestion of vegetables, spices, teas and herbal remedies from this family of plants. The evidence for the occurrence of systemic allergic dermatitis caused by sesquiterpene lactone-containing plants is mostly anecdotal...

Photoswitchable Dihydroazulene Macrocycles for Solar Energy Storage: The Effects of Ring Strain.

Science.gov (United States)

Vlasceanu, Alexandru; Frandsen, Benjamin N; Skov, Anders B; Hansen, Anne Schou; Rasmussen, Mads Georg; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted

2017-10-06

Efficient energy storage and release are two major challenges of solar energy harvesting technologies. The development of molecular solar thermal systems presents one approach to address these issues by tuning the isomerization reactions of photo/thermoswitches. Here we show that the incorporation of photoswitches into macrocyclic structures is a particularly attractive solution for increasing the storage time. We present the synthesis and properties of a series of macrocycles incorporating two dihydroazulene (DHA) photoswitching subunits, bridged by linkers of varying chain length. Independent of ring size, all macrocycles exhibit stepwise, light-induced, ring-opening reactions (DHA-DHA to DHA-VHF to VHF-VHF; VHF = vinylheptafulvene) with the first DHA undergoing isomerization with a similar efficiency as the uncyclized parent system while the second (DHA-VHF to VHF-VHF) is significantly slower. The energy-releasing, VHF-to-DHA, ring closures also occur in a stepwise manner and are systematically found to proceed slower in the more strained (smaller) cycles, but in all cases with a remarkably slow conversion of the second VHF to DHA. We managed to increase the half-life of the second VHF-to-DHA conversion from 65 to 202 h at room temperature by simply decreasing the ring size. A computational study reveals the smallest macrocycle to have the most energetic VHF-VHF state and hence highest energy density.

Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases

Energy Technology Data Exchange (ETDEWEB)

Yu, Hao; Dranchak, Patricia; Li, Zhiru; MacArthur, Ryan; Munson, Matthew S.; Mehzabeen, Nurjahan; Baird, Nathan J.; Battalie, Kevin P.; Ross, David; Lovell, Scott; Carlow, Clotilde K.S.; Suga, Hiroaki; Inglese, James (U of Tokyo); (NEB); (Kansas); (NIH); (NIST); (HHMI)

2017-04-03

Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanism placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.

Use of tetraaza-macrocycles for complexation of actinides in aqueous solutions. Validation of the process for the treatment of waste waters

International Nuclear Information System (INIS)

Chollet, Herve

1994-01-01

This report makes one's contribution to the study of the reactivity of free or fixed tetraaza-macrocycles. The major interest of this work concerns the following key-points: - Synthesis, spectral characterization and X-ray diffraction study of tetraaza-macrocycles N-tetra-functionalized, - Synthesis, physicochemical, chemicals and X-ray studies of macrocyclic complex in lanthanides and actinides series, - Synthesis and characterization of tetraaza-macrocycles grafted on organic and inorganic polymers, - Reactivity of macrocyclic ligands grafted on Merrifield's resin or silica gel in cerium, europium, uranium, plutonium and americium series, - Extraction of heavy metals in a solid-liquid process and measurements of a pilot. (author) [fr

Sesquiterpene lactones from neurolaena oaxacana

Science.gov (United States)

Passreiter; Sandoval-Ramirez; Wright

1999-08-01

Twelve sesquiterpene lactones, two new (1 and 2) and 10 known neurolenin-type germacranolides and furanoheliangolides (3-12) were isolated from Neurolaena oaxacana, and their structures were elucidated by NMR and GC-MS analysis. The chemotaxonomic importance of these findings is discussed. As N. lobata is used against dysenteries, neurolenin B (4) and a mixture of the neurolenins C (5) and D (6) were tested against Entamoeba histolytica and Giardia intestinalis.

Long Chain N-acyl Homoserine Lactone Production by Enterobacter sp. Isolated from Human Tongue Surfaces

Science.gov (United States)

Yin, Wai-Fong; Purmal, Kathiravan; Chin, Shenyang; Chan, Xin-Yue; Chan, Kok-Gan

2012-01-01

We report the isolation of N-acyl homoserine lactone-producing Enterobacter sp. isolate T1-1 from the posterior dorsal surfaces of the tongue of a healthy individual. Spent supernatants extract from Enterobacter sp. isolate T1-1 activated the biosensor Agrobacterium tumefaciens NTL4(pZLR4), suggesting production of long chain AHLs by these isolates. High resolution mass spectrometry analysis of these extracts confirmed that Enterobacter sp. isolate T1-1 produced a long chain N-acyl homoserine lactone, namely N-dodecanoyl-homoserine lactone (C12-HSL). To the best of our knowledge, this is the first isolation of Enterobacter sp., strain T1-1 from the posterior dorsal surface of the human tongue and N-acyl homoserine lactones production by this bacterium. PMID:23202161

Online Measurement of Oxygen-Dependent Enzyme Reaction Kinetics

DEFF Research Database (Denmark)

Meissner, Murray Peter; Nordblad, Mathias; Woodley, John M

2018-01-01

accurate measurement of the oxygen mass balance in the gas-phase of a reactor. The method was successfully validated and demonstrated using two model reactions: firstly the oxidation of glucose by glucose oxidase and secondly the Baeyer-Villiger oxidation of macrocyclic ketones to lactones. Initial...

Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

Science.gov (United States)

Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

2017-08-03

The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

Phytotoxic Effects and Phytochemical Fingerprinting of Hydrodistilled Oil, Enriched Fractions, and Isolated Compounds Obtained from Cryptocarya massoy (Oken) Kosterm. Bark.

Science.gov (United States)

Rolli, Enrico; Marieschi, Matteo; Maietti, Silvia; Guerrini, Alessandra; Grandini, Alessandro; Sacchetti, Gianni; Bruni, Renato

2016-01-01

The hydrodistilled oil of Cryptocarya massoy bark was characterized by GC-FID and GC/MS analyses, allowing the identification of unusual C10 massoia lactone (3, 56.2%), C12 massoia lactone (4, 16.5%), benzyl benzoate (1, 12.7%), C8 massoia lactone (3.4%), δ-decalactone (5, 1.5%), and benzyl salicylate (2, 1.8%) as main constituents. The phytotoxic activities of the oil, three enriched fractions (lactone-rich, ester-rich, and sesquiterpene-rich), and four constituents (compounds 1, 2, 5, and δ-dodecalactone (6)) against Lycopersicon esculentum and Cucumis sativus seeds and seedlings were screened. At a concentration of 1000 μl/l, the essential oil and the massoia lactone-rich fraction caused a complete inhibition of the germination of both seeds, and, when applied on tomato plantlets, they induced an 85 and 100% dieback, respectively. These performances exceeded those of the well-known phytotoxic essential oils of Syzygium aromaticum and Cymbopogon citratus, already used in commercial products for the weed and pest management. The same substances were also evaluated against four phytopathogenic bacteria and ten phytopathogenic fungi, providing EC50 values against the most susceptible strains in the 100-500 μl/l range for the essential oil and in the 10-50 μl/l range for compound 6 and the lactone-rich fraction. The phytotoxic behavior was related mainly to massoia lactones and benzyl esters, while a greater amount of 6 may infer a good activity against some phytopathogenic fungi. Further investigations of these secondary metabolites are warranted, to evaluate their use as natural herbicides. Copyright © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Characterization of N-Acylhomoserine Lactones Produced by Bacteria Isolated from Industrial Cooling Water Systems

Directory of Open Access Journals (Sweden)

Noriya Okutsu

2015-12-01

Full Text Available The cooling water systems are used to remove heat generated in the various industries. Biofouling of the cooling water systems causes blocking of condenser pipes and the heat exchanger tubes. In many Gram-negative bacteria, N-acylhomoserine lactone (AHL are used as quorum-sensing signal molecule and associated with biofilm formation. To investigate the relationship between quorum sensing and biofouling in the cooling water system, we isolated a total of 192 bacterial strains from the five cooling water systems, and screened for AHL production. Seven isolates stimulated AHL-mediated purple pigment production in AHL reporter strain Chromobacterium violaceum CV026 or VIR07. Based on their 16S rRNA gene sequences, AHL-producing isolates were assigned to Aeromonas hydrophila, Lysobacter sp., Methylobacterium oryzae, and Bosea massiliensis. To the best of our knowledge, B. massiliensis and Lysobacter sp. have not been reported as AHL-producing species in the previous researches. AHLs extracted from the culture supernatants of B. massiliensis and Lysobacter sp. were identified by liquid chromatography-mass spectrometry. AHLs produced by B. massiliensis were assigned as N-hexanoyl-l-homoserine lactone (C6-HSL, N-(3-oxohexanoyl-l-homoserine lactone (3-oxo-C6-HSL, and N-(3-oxooctanoyl-l-homoserine lactone (3-oxo-C8-HSL. AHLs produced by Lysobacter sp. were assigned as N-decanoyl-l-homoserine lactone (C10-HSL and N-(3-oxodecanoyl-l-homoserine lactone (3-oxo-C10-HSL. This is the first report of identification of AHLs produced by B. massiliensis and Lysobacter sp. isolated from the cooling water system.

Simultaneous Determination of Flavonols and Terpene Lactones in ...

African Journals Online (AJOL)

Liquid Chromatography-Tandem - Mass Spectrometry: 1. ... Results: The method showed high selectivity of the flavonols and terpene ... Lower limit of quantification (LLOQ) was 1.232, 0.240, 0.200, ... flavonoid glycosides and terpene lactones.

Lipase-catalyzed ring-opening polymerization of lactones to polyesters and its mechanistic aspects.

Science.gov (United States)

Namekawa, S; Suda, S; Uyama, H; Kobayashi, S

1999-01-01

Lipase catalysis induced a ring-opening polymerization of lactones with different ring-sizes. Small-size (four-membered) and medium-size lactones (six- and seven-membered) as well as macrolides (12-, 13-, 16-, and 17-membered) were subjected to lipase-catalyzed polymerization. The polymerization behaviors depended primarily on the lipase origin and the monomer structure. The macrolides showing much lower anionic polymerizability were enzymatically polymerized faster than epsilon-caprolactone. The granular immobilized lipase derived from Candida antartica showed extremely efficient catalysis in the polymerization of epsilon-caprolactone. Single-step terminal functionalization of the polyester was achieved by initiator and terminator methods. The enzymatic polymerizability of lactones was quantitatively evaluated by Michaelis-Menten kinetics.

Synthetic approach of norbadione A: new preparation of alcohols from sulfones and boron compounds

International Nuclear Information System (INIS)

Billaud, C.

2005-12-01

The synthetic approach of norbadione A, a pigment from mushrooms related to pulvinic acids, was studied. This compound has the property to complex caesium and has shown an antioxidant activity. The first strategy, based on a double Suzuki-Miyaura coupling between a naphtho-lactone with two boron functions and two pulvinic moieties with a triflate was unsuccessful and has shown a deactivating effect of the lactone. Modifications aimed to inhibit the electro-attracting character of the lactone permitted to obtain a bis(coupled) product with a poor yield. A second approach based on a the cyclization of enol aryl-acetates was studied in order to build the pulvinic moiety in several steps. The important reaction of introduction of an alkyl-acetate from a triflate was realised by a palladium-mediated coupling. The cyclization attempts carried out using a naphthalenic compound allowed us to isolate a monocyclised product. A parallel study was to first build a tetronic moiety and then to construct the exocyclic double bond by a method developed in the laboratory for the preparation of an iodated pulvinic compound. Finally, a new preparation of alcohols from sulfones and boron compounds was developed. Two known reactions in the chemistry of boron were combined. The first one is the reaction between anions of sulfones and tri-alkyl-boranes, the second one is a thermal isomerization which places the boron atom in a terminal position. A new preparation of primary alcohols was thus carried out. (author)

Solar Thermal Energy Storage in a Photochromic Macrocycle.

Science.gov (United States)

Vlasceanu, Alexandru; Broman, Søren L; Hansen, Anne S; Skov, Anders B; Cacciarini, Martina; Kadziola, Anders; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted

2016-07-25

The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA-DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF-VHF). A stepwise energy release over two sequential ring-closing reactions (VHF→DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long-term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards tumour targeting with copper-radiolabelled macrocycle-antibody conjugates

International Nuclear Information System (INIS)

Morphy, J.R.; Parker, David; Kataky, Ritu

1989-01-01

Tetraaza-macrocycles covalently attached to a monoclonal antibody may be efficiently radiolabelled with 64 Cu or 67 Cu at pH4, minimising non-specific binding to the protein, giving a kinetically stable conjugate in vivo. (author)

Extraction and formation dynamic of oak-related volatile compounds from different volume barrels to wine and their behavior during bottle storage.

Science.gov (United States)

Pérez-Prieto, Luis J; López-Roca, Jose M; Martínez-Cutillas, Adrián; Pardo-Mínguez, Francisco; Gómez-Plaza, Encarna

2003-08-27

The extraction rate of furfuryl aldehydes, guaiacol, and 4-methylguaiacol, cis- and trans-oak lactone, and vanillin and the formation rate of furfuryl alcohol and the volatile phenols 4-ethylguaiacol and 4-ethylphenol have been studied in wines matured in different capacity oak barrels (220, 500, and 1000 L). Also, the behavior of these compounds during 1 year of wine bottle storage was followed. The lactones were extracted at a linear rate with large differences that depended on barrel volume. Those compounds related to oak toasting (guaiacol, 4-methylguaiacol, furfuryl aldehydes, and vanillin) seemed to be extracted faster during the first days of oak maturation except for vanillin, which required at least 3 months to accumulate in the wine. The volatile phenols, 4-ethylphenol and 4-ethylguaiacol, were formed in large quantities after the first 90 days of oak maturation, coinciding with the end of spring and beginning of summer. Wines matured in 1000-L oak barrels resulted in the lowest levels of volatile compound accumulation. During bottle storage, some compounds decreased in their concentration (5-methylfurfural, vanillin), others experienced increases in their levels (lactones, furfural, 4-ethylguaiacol, 4-ethylphenol), and the concentration of other compounds hardly changed (guaiacol, furfuryl alcohol).

Triacetic acid lactone production from Saccharomyces cerevisiae

Science.gov (United States)

Triacetic acid lactone (TAL) is a potential platform chemical produced from acetyl-CoA and malonyl-CoA by the Gerbera hybrida 2-pyrone synthase (2PS) gene. Studies are ongoing to optimize production, purification, and chemical modification of TAL, which can be used to create the commercial chemicals...

Synthesis of polyhydroxylated compounds from Derythrose: enzymatic inhibition studies

OpenAIRE

Noro, Jennifer Martins

2015-01-01

Dissertação de mestrado em Química Medicinal This thesis is divided into two parts. At first, two starting synthon compounds were obtained: the benzylidene acetal D-erythrose aldehyde and the unsaturated lactone derived from this aldehyde. Both compounds were obtained following methods reported in the literature. The first part of the work focuses on aldehyde reactions with different primary aliphatic amines, yielding the respective imines. These were reduced to afford the ...

Towards tumour targeting with copper-radiolabelled macrocycle-antibody conjugates

Energy Technology Data Exchange (ETDEWEB)

Morphy, J.R.; Parker, David; Kataky, Ritu; Harrison, Alice; Walker, Carole; Eaton, M.A.W.; Millican, Andrew; Phipps, Alison

1989-06-15

Tetraaza-macrocycles covalently attached to a monoclonal antibody may be efficiently radiolabelled with /sup 64/Cu or /sup 67/Cu at pH4, minimising non-specific binding to the protein, giving a kinetically stable conjugate in vivo. (author).

Lactone Enol Cation-Radicals. Gas-Phase Generation, Structure, Energetics, and Reactivity of the Ionized Enol of Butane-4-Lactone

Czech Academy of Sciences Publication Activity Database

Tureček, F.; Vivekananda, S.; Sadílek, M.; Polášek, Miroslav

2002-01-01

Roč. 37, - (2002), s. 829-839 ISSN 1076-5174 R&D Projects: GA ČR GA203/00/0632 Institutional research plan: CEZ:AV0Z4040901 Keywords : lactone enol ions * dissociation mechanisms * isotope effects Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.781, year: 2002

Deuterium-labelled N-acyl-l-homoserine lactones (AHLs) - inter-kingdom signalling molecules - synthesis, structural studies, and interactions with model lipid membranes

International Nuclear Information System (INIS)

Jakubczyk, Dorota; Barth, Christoph; Anastassacos, Frances; Koelsch, Patrick; Schepers, Ute; Kubas, Adam; Fink, Karin; Brenner-Weiss, Gerald; Braese, Stefan

2012-01-01

N-Acyl-l-homoserine lactones (AHLs) are synthesized by Gram-negative bacteria. These quorum-sensing molecules play an important role in the context of bacterial infection and biofilm formation. They also allow communication between microorganisms and eukaryotic cells (inter-kingdom signalling). However, very little is known about the entire mechanism of those interactions. Precise structural studies are required to analyse the different AHL isomers as only one form is biologically most active. Theoretical studies combined with experimental infrared and Raman spectroscopic data are therefore undertaken to characterise the obtained compounds. To mimic interactions between AHL and cell membranes, we studied the insertion of AHL in supported lipid bilayers, using vibrational sum-frequency-generation spectroscopy. Deuterium-labelled AHLs were thus synthesized. Starting from readily available deuterated fatty acids, a two-step procedure towards deuterated N-acyl-l-homoserine lactones with varying chain lengths is described. This included the acylation of Meldrum's acid followed by amidation. Additionally, the detailed analytical evaluation of the products is presented herein. (orig.)

Patch testing with the "sesquiterpene lactone mix"

DEFF Research Database (Denmark)

Ducombs, G; Benezra, C; Talaga, P

1990-01-01

6278 patients were patch tested with a sesquiterpene lactone mix (SL-mix) in 10 European clinics. 4011 patients were tested only with 0.1% SL-mix, 63 (approximately 1.5%) of whom were positive, with 26 (41%) of these cases being considered clinically relevant. There were no cases of active...

Total synthesis of complestatin: development of a Pd(0)-mediated indole annulation for macrocyclization.

Science.gov (United States)

Shimamura, Hiroyuki; Breazzano, Steven P; Garfunkle, Joie; Kimball, F Scott; Trzupek, John D; Boger, Dale L

2010-06-09

Full details of the initial development and continued examination of a powerful intramolecular palladium(0)-mediated indole annulation for macrocyclization closure of the strained 16-membered biaryl ring system found in complestatin (1, chloropeptin II) and the definition of factors impacting its intrinsic atropodiastereoselectivity are described. Its examination and use in an alternative, second-generation total synthesis of complestatin are detailed in which the order of the macrocyclization reactions was reversed from our first-generation total synthesis. In this approach and with the ABCD biaryl ether ring system in place, the key Larock cyclization was conducted with substrate 36 (containing four phenols, five secondary amides, one carbamate, and four labile aryl chlorides) and provided the product 37 (56%) exclusively as a single atropisomer (>20:1, detection limits) possessing the natural (R)-configuration. In this instance, the complexity of the substrate and the reverse macrocyclization order did not diminish the atropodiastereoselectivity; rather, it provided an improvement over the 4:1 selectivity that was observed with the analogous substrate used to provide the isolated DEF ring system in our first-generation approach. Just as significant, the atroposelectivity represents a complete reversal of the diasteroselectivity observed with analogous macrocyclizations conducted using a Suzuki biaryl coupling.

Lactone size dependent reactivity in Candida antarctica lipase B: A molecular dynamics and docking study

NARCIS (Netherlands)

Veld, M.A.J.; Fransson, L.; Palmans, A.R.A.; Meijer, E.W.; Hult, K.

2009-01-01

Size matters: Lactones have extensively been studied as monomers in enzymatic polymerization reactions. Large lactones showed an unexpectedly high reactivity in these reactions. A combination of docking and molecular dynamics studies have been used to explain this high reactivity in terms of

Distribution of enantiomers of volatile organic compounds in selected fruit distillates.

Science.gov (United States)

Vyviurska, Olga; Zvrškovcová, Helena; Špánik, Ivan

2017-01-01

The enantiomer ratios of chiral volatile organic compounds in fruit distillates were determined by multidimensional gas chromatography using solid-phase microextraction (SPME) as a sample treatment procedure. Linalool and its oxides, limonene, α-terpineol, and nerolidol, were present at the highest concentration levels, while significantly lower amounts of β-citronellol and lactones were found in the studied samples. However, almost all terpenoids mainly occur as a racemic or near-racemic mixture; enantiomer distribution of some chiral organic compounds in fruit distillates correlated to a botanical origin. In particular, a significant enantiomeric excess of (R)-linalool and (S)-α-terpineol was found only for pear brandy, and likewise the dominance (R)-limonene and the second eluted enantiomer of nerolidol for Sorbus domestica and strawberry, respectively. The distribution of γ-lactones stereoisomers was more nonspecific, with a general excess of the R-enantiomer. © 2016 Wiley Periodicals, Inc.

Sesquiterpene lactones. XXXVI. Sesquiterpene lactones in several subgenera of the genus Centaurea L.

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Gerard Nowak

2014-01-01

Full Text Available The occurrence of both known and new sesquiterpene lactones was determined in six species classified in different subgenera of Centaurea L. Chlorojanerin, cynaropicrin and janerin were isolated from C. phaeopappoides Bordz. and C. thracica (Janka Hayek. C. marschalliana Spreng. was found to contain acroptilin, chlorojanerin, cebellin D and janerin while C. adjarica Alb. had repin, acroptilin, chlorojanerin, centaurepensin, janerin, repidiolide, cebellin D, E, F and L A new, hitherto underscribed cebellin J quaianolide was found in C. bella Trautv. and another germacranolide, 3α, 15-dihydroxycostunolide was found in C. sphaerocephala subsp. lusitanica (Boiss. et Reuter Nyman.

Example of uranium(IV) insertion within a macrocyclic crown ether with coexistence of the metal in two oxidation states

Energy Technology Data Exchange (ETDEWEB)

Bombieri, G; De Paoli, G [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi; Immirzi, A

1978-01-01

Reaction of UCl/sub 4/ with 18-crown-6 in tetrahydrofuran yields (UCl/sub 4/)/sub 3/ (18-crown-6)/sub 2/ which on recrystallization in nitromethane, gives a partially oxidized and hydrolyzed product whose structure has been investigated by X-ray diffraction. The compound crystallizes in the orthorhombic system. The cell contains eight UCl/sub 3//sup +/ cations each inserted within a crown molecule and four (UO/sub 2/Cl/sub 3/(OH)(H/sub 2/O))/sup 2 -/anions having a pentagonal bipyramidal structure. Four solvated nitromethane molecules are also present. The compound represents one of the very few examples in which uranium exists in two oxidation states, and the first example in which its insertion within a crown macrocycle has been proved by an X-ray diffraction study.

Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

Science.gov (United States)

Inayat-Hussain, S H; Annuar, B O; Din, L B; Ali, A M; Ross, D

2003-08-01

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

Paraoxonase (PON1 and PON3 polymorphisms: impact on liver expression and atorvastatin-lactone hydrolysis

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Stephan eRiedmaier

2011-07-01

Full Text Available Atorvastatin δ-lactone, a major, pharmacologically inactive metabolite, has been associated with toxicity. In a previous study we showed that polymorphisms of UGT1A3 influence atorvastatin δ-lactone formation. Here we investigated the reverse reaction, atorvastatin δ-lactone hydrolysis, in a human liver bank. Screening of microarray data revealed paraoxonases PON1 and PON3 among 17 candidate esterases. Microsomal δ-lactone hydrolysis was significantly correlated to PON1 and PON3 protein (rs=0.60; rs=0.62, respectively; P<0.0001. PON1 and PON3 were strongly correlated to each other (rs=0.60 but PON1 was shown to be more extensively glycosylated than PON3. In addition a novel splice variant of PON3 was identified. Genotyping of 40 polymorphisms within the PON-locus identified PON1 promoter polymorphisms (-108T>C, -832G>A, -1741G>A and a tightly linked group of PON3 polymorphisms (-4984A>G, -4105G>A, -1091A>G, -746C>T and F21F to be associated with changes in atorvastatin δ-lactone hydrolysis and expression of PON1 but not PON3. However, carriers of the common PON1 polymorphisms L55M or Q192R showed no difference in δ-lactone hydrolysis or PON expression. Haplotype analysis revealed decreased δ-lactone hydrolysis in carriers of the most common haplotype *1 compared to carriers of haplotypes *2, *3, *4 and *7. Analysis of non-genetic factors showed association of hepatocellular and cholangiocellular carcinoma with decreased PON1 and PON3 expression, respectively. Increased C-reactive protein and γ-glutamyl transferase levels were associated with decreased protein expression of both enzymes, and increased bilirubin levels, cholestasis and pre-surgical exposure to omeprazole or pantoprazole were related to decreased PON3 protein. In conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic factors have an effect on PON1 and PON3 expression. This may influence response to therapy or adverse events in statin treatment.

Unusual Multiple Production of N-Acylhomoserine Lactones a by Burkholderia sp. Strain C10B Isolated from Dentine Caries

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Share Yuan Goh

2014-05-01

Full Text Available Bacteria realize the ability to communicate by production of quorum sensing (QS molecules called autoinducers, which regulate the physiological activities in their ecological niches. The oral cavity could be a potential area for the presence of QS bacteria. In this study, we report the isolation of a QS bacterial isolate C10B from dentine caries. Preliminary screening using Chromobacterium violaceum CV026 biosensor showed that isolate C10B was able to produce N-acylhomoserine lactones (AHLs. This bacterium was further identified as a member of Burkholderia, an opportunistic pathogen. The isolated Burkholderia sp. was confirmed to produce N-hexanoyl-L-homoserine lactone (C6-HSL, N-octanoyl-L-homoserine lactone (C8-HSL, N-decanoyl-L-homoserine lactone (C10-HSL and N-dodecanoyl-L-homoserine lactone (C12-HSL.

A strategic approach to [6,6]-bicyclic lactones

DEFF Research Database (Denmark)

Jepsen, Tue Heesgaard; Glibstrup, Emil; Crestey, Francois Louis Jean

2017-01-01

We report an effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki–Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of the elusive CD fragment of the Erythrina...

Antibacterial and cytotoxic activities of the sesquiterpene lactones cnicin and onopordopicrin.

Science.gov (United States)

Bach, Sandra M; Fortuna, Mario A; Attarian, Rodgoun; de Trimarco, Juliana T; Catalán, César A N; Av-Gay, Yossef; Bach, Horacio

2011-02-01

The antimicrobial and cytotoxic activities of chloroform extracts from the weeds Centaurea tweediei and C. diffusa, and the main sesquiterpene lactones isolated from these species, onopordopicrin and cnicin, respectively, were assayed. Results show that the chloroform extracts from both Centaurea species possess antibacterial activities against a panel of Gram-positive and Gram-negative bacteria. Remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus was also measured. Both the extracts and the purified sesquiterpene lactones show high cytotoxicity against human-derived macrophages. Despite this cytotoxicity, C. diffusa chloroform extract and cnicin are attractive candidates for evaluation as antibiotics in topical preparations against skin-associated pathogens.

An unusual mono-substituted Keggin anion-chain based 3D framework with 24-membered macrocycles as linker units

International Nuclear Information System (INIS)

Pang Haijun; Ma Huiyuan; Yu Yan; Yang Ming; Xun Ye; Liu Bo

2012-01-01

A new compound, [Cu I (H 2 O)(Hbpp) 2 ]⊂{[Cu I (bpp)] 2 [PW 11 Cu II O 39 ]} (1) (bpp=1,3-bis(4-pyridyl)propane), has been hydrothermally synthesized and structurally characterized by single crystal X-ray diffraction. In compound 1, the unusual –A–B–A–B– array mono-substituted Keggin anion-chains and 24-membered (Cubpp) 2 cation-macrocycles are linked together to form a (2, 4) connected 3D framework with channels of ca. 9.784×7.771 Å 2 along two directions, in which the [Cu(H 2 O)(Hbpp) 2 ] coordination fragments as guest components are trapped. The photocatalytic experiments of compound 1 were performed, which show a good catalytic activity of compound 1 for photodegradation of RhB. Furthermore, the IR, TGA and electrochemical properties of compound 1 were investigated. - Graphical abstract: An unusual example of mono-substituted Keggin anion-chain based hybrid compound that possesses a 3D structure has been synthesized, which offers a feasible route for synthesis of such compounds. Highlights: ► The first example of –A–B–A–B– array mono-substituted Keggin chain is observed. ► An unusual three dimensional structure based mono-substituted Keggin anion-chains. ► The photocatalysis and electrochemical properties of the title compound were studied.

Sesquiterpene Lactones of Amphoricarpos autariatus ssp. autariatus from Montenegro - Antifungal Leaf - Surface Constituents

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Milka Jadranin

2013-05-01

Full Text Available The composition of leaf cuticular neutral lipids of Amphoricarpos autariatus ssp. autariatus collected at canyon of river Tara (North Montenegro was investigated by GC/MS (nonpolar fraction, LC-ESI TOF MS and 1H NMR spectroscopy (more polar fraction. The nonpolar fraction (ca. 15% of the whole surface extract contained C 27 - 33 n-alkanes, those with odd-number of carbons predominating. The LC-ESI MS and 1H NMR of the more polar fraction revealed 13 sesquiterpene lactones, constituting ca. 97.5% of the lactone mixture, identified as the known guaianolides, so-called amphoricarpolides, found previously in the aerial parts of the genus. The lactone fraction exhibited considerable in vitro effect against eight fungi, i.e. Aspergillus ochraceus , A. niger, A. versicolor , Penicillium funiculosum, P. ochrochloron, Trichoderma viride, Fusarium verticillioides and Fulvia fulvum.

Dysprosium complexes with the tetraphenylporphyrin macrocyclic ligand

International Nuclear Information System (INIS)

Martinez M, V.; Padilla, J.; Ramirez, F.M.

1992-04-01

In this report, the results obtained on the synthesis, characterization and study of the chemical behavior of dysprosium complex with the acetylacetone chelating agent (Hacac) and the tetraphenylporphyrin macrocyclic ligand (H 2 TFP) are given. Based on the literature but according to our necessities and interest, the appropriate methodology settled down from the synthesis of prime matters until the obtaining and characterization of the products. The acetyl acetonate complex was obtained of mono hydrated dysprosium [Dy(acac) 3 . H 2 0] and trihydrated [Dy(acac) 3 .3 H 2 0], the mono tetra phenyl porphyrinate [Dy(TFP)(acac). 2 ac] the double sandwich of the dysprosium porphyrinate [Dy(TFP) 2 ] and the triple sandwich of the dysprosium porphyrinate [Dy(TFP) 3 . 2 TCB] (TCB = trichlorobenzene). Its were characterized by their melting points, solubility, IR, UV, TGA and DTA both first and besides the techniques already mentioned for NMR'H, RPE and Magnetic susceptibility the three last complexes. From the spectroscopic point of view, IR and RPE its suggested the existence of a complex of inverse mixed valence [Dy(TFP) 2- (TFP) 1- ] for the Dy(TFP) 2 as a result of the existence of the free radical (TFP' 1- and that it was not in none of the other porphyrin compounds. In the NMR'H spectra of the compounds were not observed signals in the region from 0 to 10 ppm that which shows that the dysprosium complexes in special those of the porphyrin type are highly paramagnetic and its could be used as displacement reagents, creators of images and contrast agents of great utility in these days in studies of NMR, technique today by today used in medical diagnoses. (Author)

Aroma compounds in sweet whey powder.

Science.gov (United States)

Mahajan, S S; Goddik, L; Qian, M C

2004-12-01

Aroma compounds in sweet whey powder were investigated in this study. Volatiles were isolated by solvent extraction followed by solvent-assisted flavor evaporation. Fractionation was used to separate acidic from nonacidic volatiles. Gas chromatography/mass spectrometry and gas chromatography/olfactometry were used for the identification of aroma compounds. Osme methodology was applied to assess the relative importance of each aroma compound. The most aroma-intense free fatty acids detected were acetic, propanoic, butanoic, hexanoic, heptanoic, octanoic, decanoic, dodecanoic, and 9-decenoic acids. The most aroma-intense nonacidic compounds detected were hexanal, heptanal, nonanal, phenylacetaldehyde, 1-octen-3-one, methional, 2,6-dimethylpyrazine, 2,5-dimethylpyrazine, 2,3-dimethylpyrazine, 2,3,5-trimethylpyrazine, furfuryl alcohol, p-cresol, 2-acetylpyrrole, maltol, furaneol, and several lactones. This study suggested that the aroma of whey powder could comprise compounds originating from milk, compounds generated by the starter culture during cheese making, and compounds formed during the manufacturing process of whey powder.

Quantitative Structure ‒ Antiprotozoal Activity Relationships of Sesquiterpene Lactones

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Reto Brun

2009-06-01

Full Text Available Prompted by results of our previous studies where we found high activity of some sesquiterpene lactones (STLs against Trypanosoma brucei rhodesiense (which causes East African sleeping sickness, we have now conducted a structure-(in-vitro-activity study on a set of 40 STLs against T. brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. Furthermore, cytotoxic activity against L6 rat skeletal myoblast cells was assessed. Some of the compounds possess high activity, especially against T. brucei (e.g. helenalin and some of its esters with IC50-values of 0.05-0.1 µM, which is about 10 times lower than their cytotoxic activity. It was found that all investigated antiprotozoal activities are significantly correlated with cytotoxicity and the major determinants for activity are a,b-unsaturated structural elements, also known to be essential for other biological activities of STLs. It was observed, however, that certain compounds are considerably more toxic against protozoa than against mammalian cells while others are more cytotoxic than active against the protozoa. A comparative QSAR analysis was therefore undertaken, in order to discern the antiparasitic activity of STLs against T. brucei and cytotoxicity. Both activities were found to depend to a large extent on the same structural elements and molecular properties. The observed variance in the biological data can be explained in terms of subtle variations in the relative influences of various molecular descriptors.

Trypanocidal Activity of Smallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation

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F. M. Frank

2013-01-01

Full Text Available In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1, uvedalin (2, and polymatin B (3 by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 μM (1, 1.09 μM (2, and 4.90 μM (3. After a 24 h treatment with 10 μg/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33.4 μM and 25.0 μM against T. cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 μM, 3.34 μM, and 9.02 μM for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 μM (1, 46.8 μM (2, and 147.3 μM (3 and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs.

Genetic and biochemical characterization of a novel monoterpene epsilon-lactone hydrolase from Rhodococcus erythropolis DCL14

NARCIS (Netherlands)

Vlugt-Bergmans, van der C.J.B.; Werf, van der M.J.

2001-01-01

A monoterpene ε-lactone hydrolase (MLH) from Rhodococcus erythropolis DCL14, catalyzing the ring opening of lactones which are formed during degradation of several monocyclic monoterpenes, including carvone and menthol, was purified to apparent homogeneity. It is a monomeric enzyme of 31 kDa that is

Genetic and biochemical characterization of a novel monoterpene e-lactone hydrolase from Rhodococcus erythropolis DCL14

NARCIS (Netherlands)

Vlugt-Bergmans, C.J.B. van der; Werf, M.J. van der

2001-01-01

A monoterpene ε-lactone hydrolase (MLH) from Rhodococcus erythropolis DCL14, catalyzing the ring opening of lactones which are formed during degradation of several monocyclic monoterpenes, including carvone and menthol, was purified to apparent homogeneity. It is a monomeric enzyme of 31 kDa that is

On-Surface Pseudo-High-Dilution Synthesis of Macrocycles: Principle and Mechanism.

Science.gov (United States)

Fan, Qitang; Wang, Tao; Dai, Jingya; Kuttner, Julian; Hilt, Gerhard; Gottfried, J Michael; Zhu, Junfa

2017-05-23

Macrocycles have attracted much attention due to their specific "endless" topology, which results in extraordinary properties compared to related linear (open-chain) molecules. However, challenges still remain in their controlled synthesis with well-defined constitution and geometry. Here, we report the successful application of the (pseudo-)high-dilution method to the conditions of on-surface synthesis in ultrahigh vacuum. This approach leads to high yields (up to 84%) of cyclic hyperbenzene ([18]-honeycombene) via an Ullmann-type reaction from 4,4″-dibromo-meta-terphenyl (DMTP) as precursor on a Ag(111) surface. The mechanism of macrocycle formation was explored in detail using scanning tunneling microscopy and X-ray photoemission spectroscopy. We propose that the dominant pathway for hyperbenzene (MTP) 6 formation is the stepwise desilverization of an organometallic (MTP-Ag) 6 macrocycle, which forms via cyclization of (MTP-Ag) 6 chains under pseudo-high-dilution conditions. The high probability of cyclization on the stage of the organometallic phase results from the reversibility of the C-Ag bond. The case is different from that in solution, in which cyclization typically occurs on the stage of a covalently bonded open-chain precursor. This difference in the cyclization mechanism on a surface compared to that in solution stems mainly from the 2D confinement exerted by the surface template, which hinders the flipping of chain segments necessary for cyclization.

Simultaneous Determination of Flavonols and Terpene Lactones in ...

African Journals Online (AJOL)

Lactones in Beagle Dog Plasma by Ultra-Performance ... School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, ... Matrix effect derived from QC samples was in the range of 85.09 – 113.14 %. ..... with the suitable weighting factor of 1/x. .... pharmacokinetic studies of G. biloba and its.

Deuterium-labelled N-acyl-l-homoserine lactones (AHLs) - inter-kingdom signalling molecules - synthesis, structural studies, and interactions with model lipid membranes

Energy Technology Data Exchange (ETDEWEB)

Jakubczyk, Dorota [Institute of Organic Chemistry, Karlsruhe Institute of Technology, Karlsruhe (Germany); Institute of Functional Interfaces, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Barth, Christoph; Anastassacos, Frances; Koelsch, Patrick; Schepers, Ute [Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Kubas, Adam; Fink, Karin [Institute of Nanotechnology, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Brenner-Weiss, Gerald [Institute of Functional Interfaces, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Braese, Stefan [Institute of Organic Chemistry, Karlsruhe Institute of Technology, Karlsruhe (Germany)

2012-04-15

N-Acyl-l-homoserine lactones (AHLs) are synthesized by Gram-negative bacteria. These quorum-sensing molecules play an important role in the context of bacterial infection and biofilm formation. They also allow communication between microorganisms and eukaryotic cells (inter-kingdom signalling). However, very little is known about the entire mechanism of those interactions. Precise structural studies are required to analyse the different AHL isomers as only one form is biologically most active. Theoretical studies combined with experimental infrared and Raman spectroscopic data are therefore undertaken to characterise the obtained compounds. To mimic interactions between AHL and cell membranes, we studied the insertion of AHL in supported lipid bilayers, using vibrational sum-frequency-generation spectroscopy. Deuterium-labelled AHLs were thus synthesized. Starting from readily available deuterated fatty acids, a two-step procedure towards deuterated N-acyl-l-homoserine lactones with varying chain lengths is described. This included the acylation of Meldrum's acid followed by amidation. Additionally, the detailed analytical evaluation of the products is presented herein. (orig.)

Coherent anti-Stokes Raman scattering (CARS) spectroscopy in Caenorhabditis elegans and Globodera pallida: evidence for an ivermectin-activated decrease in lipid stores.

Science.gov (United States)

Smus, Justyna P; Ludlow, Elizabeth; Dallière, Nicolas; Luedtke, Sarah; Monfort, Tual; Lilley, Catherine; Urwin, Peter; Walker, Robert J; O'Connor, Vincent; Holden-Dye, Lindy; Mahajan, Sumeet

2017-12-01

Macrocyclic lactones are arguably the most successful chemical class with efficacy against parasitic nematodes. Here we investigated the effect of the macrocyclic lactone ivermectin on lipid homeostasis in the plant parasitic nematode Globodera pallida and provide new insight into its mode of action. A non-invasive, non-destructive, label-free and chemically selective technique called Coherent anti-Stokes Raman scattering (CARS) spectroscopy was used to study lipid stores in G. pallida. We optimised the protocol using the free-living nematode Caenorhabditis elegans and then used CARS to quantify lipid stores in the pre-parasitic, non-feeding J2 stage of G. pallida. This revealed a concentration of lipid stores in the posterior region of J2 s within 24 h of hatching which decreased to undetectable levels over the course of 28 days. We tested the effect of ivermectin on J2 viability and lipid stores. Within 24 h, ivermectin paralysed J2 s. Counterintuitively, over the same time-course ivermectin increased the rate of depletion of J2 lipid, suggesting that in ivermectin-treated J2 s there is a disconnection between the energy requirements for motility and metabolic rate. This decrease in lipid stores would be predicted to negatively impact on J2 infective potential. These data suggest that the benefit of macrocyclic lactones as seed treatments may be underpinned by a multilevel effect involving both neuromuscular inhibition and acceleration of lipid metabolism. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Exploring the Binding of Barbital to a Synthetic Macrocyclic Receptor; a Charge Density Study

DEFF Research Database (Denmark)

Du, Jonathan J.; Hanrahan, Jane Rouse; Solomon, V. Raja

2018-01-01

Experimental charge density distribution studies, complemented by quantum mechanical theoretical calculations, of a host-guest system comprised of a macrocycle (1) and barbital (2) in a 1:1 ratio (3) have been carried out via high resolution single crystal X-ray diffraction. The data was modelled...... molecule. Visual comparison of the conformations of the macrocyclic ring shows the rotation by 180° of an amide bond attributed to competitive hydrogen bonding. It was found the intraannular and extraannular molecules inside were orientated to maximise the number of hydrogen bonds present...

Onchocerca Volvulus: Effects of Annual Treatment with Ivermectin ...

African Journals Online (AJOL)

As an alternative to vector control, chemotherapy – based control has been revolutionized by the finding that ivermectin, a novel semi synthetic macrocyclic lactone, is safe and acceptable for mass ... The prevalence rate of infection obtained at post-treatment 2 was 9.1% while the intensity rate was 1.1mf/mg skin snip.

Broflanilide: A meta-diamide insecticide with a novel mode of action.

Science.gov (United States)

Nakao, Toshifumi; Banba, Shinichi

2016-02-01

Broflanilide is a meta-diamide [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamide] that exhibits high larvicidal activity against Spodoptera litura. It has been suggested that broflanilide is metabolized to desmethyl-broflanilide and that it acts as a noncompetitive resistant-to-dieldrin (RDL) γ-aminobutyric acid (GABA) receptor antagonist. The binding site of desmethyl-broflanilide was demonstrated to be distinct from that of conventional noncompetitive antagonists such as fipronil. It has been proposed that the site of action for desmethyl-broflanilide is close to G336 in the M3 region of the Drosophila RDL GABA receptor. However, although the site of action for desmethyl-broflanilide appears to overlap with that of macrocyclic lactones, different modes of actions have been demonstrated for desmethyl-broflanilide and the macrocyclic lactones. The mechanisms underlying the high selectivity of meta-diamides are also discussed in this review. Broflanilide is expected to become a prominent insecticide because it is effective against pests with resistance to cyclodienes and fipronil. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antiprotozoal Activity of α,β-Unsaturated δ-Lactones: Promising ...

African Journals Online (AJOL)

Erah

2011-03-24

, A.A 1226, Medellín, Colombia. Abstract. The parasite resistance .... respectively, and cytotoxicity on U-937 cells with LD50 of 2.1 and 1.0 µg/mL, .... to the lipophilic central chain joining the lactone rings. However, the central ...

Sesquiterpene lactones of Vernonia - influence of glaucolide-A on the growth rate and survival of Lepidopterous larvae.

Science.gov (United States)

Jones, Samuel B; Burnett, William C; Coile, Nancy C; Mabry, Tom J; Betkouski, M F

1979-01-01

Sesquiterpene lactone glaucolide-A from Vernonia, incorporated in the rearing diets of five species of Lepidoptera, significantly reduced the rate of growth of larvae of the southern armyworm, Spodoptera eridania; fall armyworm, S. frugiperda; and yellowstriped armyworm, S. ornithogalli. Quantitative feeding tests demonstrated that decreased feeding levels and reduced growth resulted from ingestion of a sesquiterpene lactone. Ingestion of glaucolide-A increased the number of days to pupation in four of the species. In the southern armyworm, it significantly reduced pupal weight. Glaucolide-A decidedly reduced percentage of survival of southern and fall armyworms. Yellow woollybear, Diacrisia virginica, and cabbage looper, Trichoplusia ni, larvae were essentially uneffected by the ingestion of the sesquiterpene lactone. Sesquiterpene lactones adversely affect growth rate and survival of certain insects that feed upon plants containing them. They apparently function as defensive products, screening out a portion of the potential herbivores.

Chemical and Biological Significance of Oenothein B and Related Ellagitannin Oligomers with Macrocyclic Structure

Directory of Open Access Journals (Sweden)

Takashi Yoshida

2018-03-01

Full Text Available In 1990, Okuda et al. reported the first isolation and characterization of oenothein B, a unique ellagitannin dimer with a macrocyclic structure, from the Oenothera erythrosepala leaves. Since then, a variety of macrocyclic analogs, including trimeric–heptameric oligomers have been isolated from various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae. Among notable in vitro and in vivo biological activities reported for oenothein B are antioxidant, anti-inflammatory, enzyme inhibitory, antitumor, antimicrobial, and immunomodulatory activities. Oenothein B and related oligomers, and/or plant extracts containing them have thus attracted increasing interest as promising targets for the development of chemopreventive agents of life-related diseases associated with oxygen stress in human health. In order to better understand the significance of this type of ellagitannin in medicinal plants, this review summarizes (1 the structural characteristics of oenothein B and related dimers; (2 the oxidative metabolites of oenothein B up to heptameric oligomers; (3 the distribution of oenotheins and other macrocyclic analogs in the plant kingdom; and (4 the pharmacological activities hitherto documented for oenothein B, including those recently found by our laboratory.

Structure-cytotoxicity relationships of some helenanolide-type sesquiterpene lactones

NARCIS (Netherlands)

Beekman, AC; Woerdenbag, HJ; vanUden, W; Pras, N; Konings, AWT; Wikstrom, HV; Schmidt, TJ

This study deals with the cytotoxicity of helenanolide-type (10 alpha-methylpseudoguaianolide) sesquiterpene lactones. We determined the influence of substitution patterns on the toxicity of 21 helenanolides to a cloned Ehrlich ascites tumor cell line, EN2. Within a series of helenalin esters, the

Versatile Multicomponent Reaction Macrocycle Synthesis Using α-Isocyano-ω-carboxylic Acids

NARCIS (Netherlands)

Liao, George P; Abdelraheem, Eman M M; Neochoritis, Constantinos G; Kurpiewska, Katarzyna; Kalinowska-Tłuścik, Justyna; McGowan, David C; Dömling, Alexander

2015-01-01

The direct macrocycle synthesis of α-isocyano-ω-carboxylic acids via an Ugi multicomponent reaction is introduced. This multicomponent reaction (MCR) protocol differs by being especially short, convergent, and versatile, giving access to 12-22 membered rings.

Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors

DEFF Research Database (Denmark)

Pehere, A.D.; Pietsch, M.; Gütschow, M.

2013-01-01

of their activity against a panel of proteases. Acyclic azidoalkyne-based aldehydes are also evaluated for comparison. The macrocyclic peptidomimetics showed considerable activity towards calpain II, cathepsin L and S, and the 20S proteasome chymotrypsin-like activity. Some of the first examples of highly potent...

Determination of ursolic acid and ursolic acid lactone in the leaves of Eucalyptus tereticornis by HPLC

International Nuclear Information System (INIS)

Maurya, Anupam; Srivastava, Santosh Kumar

2012-01-01

A simple isocratic HPLC method has been developed for the simultaneous quantification of two bioactive triterpenes, ursolic acid and ursolic acid lactone in E. tereticornis leaves. Samples were analyzed on RP-18 (4.6 x 250 mm, 5 m u m ) column with methanol and water acidified to pH 3.5 with TFA (88:12) at 210 nm. The method was validated and applied for the simultaneous quantification of the individual triterpenes in E. tereticornis extract. The calibration curves were linear over a concentration range of 0.05-0.3 mg mL -1 (r = 0.999 and 0.998, respectively). The limits of detection and quantification were 0.190 and 0.644 μg for ursolic acid, and 0.176 and 0.587 μg for ursolic acid lactone, while the percentage recoveries were 97.32 and 96.23% for ursolic acid and ursolic acid lactone, respectively. This is the first report on the HPLC method of ursolic acid lactone with high precision and accuracy. (author)

Determination of ursolic acid and ursolic acid lactone in the leaves of Eucalyptus tereticornis by HPLC

Energy Technology Data Exchange (ETDEWEB)

Maurya, Anupam; Srivastava, Santosh Kumar [Analytical Chemistry Division, Central Institute of Medicinal and Aromatic Plants, Lucknow (India)

2012-03-15

A simple isocratic HPLC method has been developed for the simultaneous quantification of two bioactive triterpenes, ursolic acid and ursolic acid lactone in E. tereticornis leaves. Samples were analyzed on RP-18 (4.6 x 250 mm, 5 {sup m}u{sup m}) column with methanol and water acidified to pH 3.5 with TFA (88:12) at 210 nm. The method was validated and applied for the simultaneous quantification of the individual triterpenes in E. tereticornis extract. The calibration curves were linear over a concentration range of 0.05-0.3 mg mL{sup -1} (r = 0.999 and 0.998, respectively). The limits of detection and quantification were 0.190 and 0.644 {mu}g for ursolic acid, and 0.176 and 0.587 {mu}g for ursolic acid lactone, while the percentage recoveries were 97.32 and 96.23% for ursolic acid and ursolic acid lactone, respectively. This is the first report on the HPLC method of ursolic acid lactone with high precision and accuracy. (author)

Zn and Fe complexes containing a redox active macrocyclic biquinazoline ligand.

Science.gov (United States)

Banerjee, Priyabrata; Company, Anna; Weyhermüller, Thomas; Bill, Eckhard; Hess, Corinna R

2009-04-06

A series of iron and zinc complexes has been synthesized, coordinated by the macrocyclic biquinazoline ligand, 2-4:6-8-bis(3,3,4,4-tetramethyldihydropyrrolo)-10-15-(2,2'-biquinazolino)-[15]-1,3,5,8,10,14-hexaene-1,3,7,9,11,14-N(6) (Mabiq). The Mabiq ligand consists of a bipyrimidine moiety and two dihydropyrrole units. The electronic structures of the metal-Mabiq complexes have been characterized using spectroscopic and density-functional theory (DFT) computational methods. The parent zinc complex exhibits a ligand-centered reduction to generate the metal-coordinated Mabiq radical dianion, establishing the redox non-innocence of this ligand. Iron-Mabiq complexes have been isolated in three oxidation states. This redox series includes low-spin ferric and low-spin ferrous species, as well as an intermediate-spin Fe(II) compound. In the latter complex, the iron ion is antiferromagnetically coupled to a Mabiq-centered pi-radical. The results demonstrate the rich redox chemistry and electronic properties of metal complexes coordinated by the Mabiq ligand.

Kinetics of oxidation of nickel(II) aza macrocycles by ...

Indian Academy of Sciences (India)

The kinetics of the oxidation of nickel (II) hexaaza and nickel (II) pentaaza macrocycles by the peroxydisulphate anion, S2O8 2-, were studied in aqueous media. Effect of H on reaction rate was also studied. The rate increases with increase of S2OO8 2- concentration. Rates are almost independent of acid between H 4 ...

Searching for a path towards a helicene-based macrocycle

Czech Academy of Sciences Publication Activity Database

Houska, Václav; Stará, Irena G.; Starý, Ivo

2017-01-01

Roč. 15, č. 1 (2017), s. 9-10 ISSN 2336-7202. [Mezioborové setkání mladých biologů, biochemiků a chemiků /17./. 30.05.2017-01.06.2017, Milovy] R&D Projects: GA ČR(CZ) GA16-08294S Institutional support: RVO:61388963 Keywords : helicenes * macrocycles Subject RIV: CC - Organic Chemistry

gfp-based N-acyl homoserine-lactone sensor systems for detection of bacterial communication

DEFF Research Database (Denmark)

Andersen, Jens Bo; Heydorn, Arne; Hentzer, Morten

2001-01-01

In order to perform single-cell analysis and online studies of N-acyl homoserine lactone (AHL)-mediated communication among bacteria, components of the Vibrio fischeri quorum sensor encoded by luxR-P-luxI have been fused to modified versions of gfpmut3* genes encoding unstable green fluorescent...... proteins. Bacterial strains harboring this green fluorescent sensor detected a broad spectrum of AHL molecules and were capable of sensing the presence of 5 nM N-3-oxohexanoyl-L-homoserine lactone in the surroundings. In combination with epifluorescent microscopy, the sensitivity of the sensor enabled AHL...

Convergent Synthesis of Rigid Macrocycles Containing One and Two Tetrathiafulvalene Units

DEFF Research Database (Denmark)

Simonsen, Klaus B.; Thorup, Niels; Becher, Jan

1997-01-01

The synthesis of rigid tetrathiafulvalenophanes containing one or two tetrathiafulvalene units is presented, together with a stepwise convergent synthesis of macrocyclic bis-tetrathiafulvalenes via several open dimeric tetrathiafulvalenes. These systems were investigated by cyclic voltammetry...... and by X-ray crystallography....

Immobilized copper(II) macrocyclic complex on MWCNTs with antibacterial activity

Energy Technology Data Exchange (ETDEWEB)

Tarlani, Aliakbar, E-mail: Tarlani@ccerci.ac.ir [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Narimani, Khashayar [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Mohammadipanah, Fatemeh; Hamedi, Javad [Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran 14155-6455 (Iran, Islamic Republic of); University of Tehran Biocompound Collection (UTBC), Microbial Technology and Products Research Center, University of Tehran, Tehran (Iran, Islamic Republic of); Tahermansouri, Hasan [Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol (Iran, Islamic Republic of); Amini, Mostafa M. [Department of Chemistry, Shahid Behshti University, 1983963113, Tehran (Iran, Islamic Republic of)

2015-06-30

Graphical abstract: In an antibacterial test, grafted copper(II) macrocyclic complex on the surface of MWCNT showed higher antibacterial activity against Bacillus subtilis compared to the individual MWCNT-COOH and the complex. - Highlights: • Copper(II) tetraaza macrocyclic complex covalently bonded to modified MWCNT. • Grafting of the complex carried out via an interaction between −C(=O)Cl group and NH of the ligand. • The samples were subjected in an antibacterial assessment to compare their activity. • Immobilized complex showed higher antibacterial activity against Bacillus subtilis ATCC 6633 compared to separately MWCNT-C(C=O)-OH and CuTAM. - Abstract: In a new approach, a copper(II) tetraaza macrocyclic complex (CuTAM) was covalently bonded on modified multi-walled carbon nanotubes (MWCNTs). To achieve this purpose, MWCNTs were converted to MWCNT-COCl and then reacted to NH groups of TAM ligand. The prepared material was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Raman spectroscopy, thermal gravimetric analysis (TGA), and FESEM (field emission scanning electron microscopy). FT-IR and TGA demonstrated the presence of the organic moieties, and XRD proved that the structure of MWCNTs remained intact during the three modification steps. An increase in the I{sub D}/I{sub G} ratio in Raman spectra confirmed the surface modifications. Finally, the samples were subjected to an antibacterial assessment to compare their biological activity. The antibacterial test showed that the grafted complex on the surface of the nanotube (MWCNT-CO-CuTAM) has higher antibacterial activity against Bacillus subtilis ATCC 6633 than the MWCNT-COOH and CuTAM with 1000 and 2000 μg/mL.

Synthesis of novel O-acylated-D-ribono-1,5-lactones and structural assignment supported by conventional NOESY-NMR and X-ray analysis

Energy Technology Data Exchange (ETDEWEB)

Sa, Marcus M.; Silveira, Gustavo P.; Caro, Miguel S.B. [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Quimica]. E-mail: msa@qmc.ufsc.br; Ellena, Javier [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Inst. de Fisica

2008-07-01

A practical method for the structural assignment of 3,4-O-benzylidene-D-ribono-1,5-lactones and analogues using conventional NMR techniques and NOESY measurements in solution is described. 2-O-Acyl-3,4-O-benzylidene-D-ribono-1,5-lactones were prepared in good yields by acylation of Zinner's lactone with acyl chlorides under mildly basic conditions. Structural determination of 2-O-(4-nitrobenzoyl)-3,4-O-benzylidene-D-ribono-1,5-lactone was achieved by single crystal x-ray diffraction, which supports the results based on spectroscopic data. (author)

Imaging N-acyl homoserine lactone quorum sensing in vivo

DEFF Research Database (Denmark)

Christensen, Louise Dahl; van Gennip, Maria; Jakobsen, Tim Holm

2011-01-01

In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

Imaging N-acyl homoserine lactone quorum sensing in vivo

DEFF Research Database (Denmark)

Hultqvist, Louise Dahl; Alhede, Maria; Jakobsen, Tim Holm

2018-01-01

In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

Triacetic acid lactone production in industrial Saccharomyces yeast strains

Science.gov (United States)

Triacetic acid lactone (TAL) is a potential platform chemical that can be produced in yeast. To evaluate the potential for industrial yeast strains to produce TAL, the g2ps1 gene encoding 2-pyrone synthase was transformed into thirteen industrial yeast strains of varied genetic background. TAL produ...

Protocols for the Design of Kinase-focused Compound Libraries.

Science.gov (United States)

Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

2018-05-01

Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and synthesis of binucleating macrocyclic clefts derived from Schiff-base calixpyrroles.

Science.gov (United States)

Givaja, Gonzalo; Volpe, Manuel; Leeland, James W; Edwards, Michael A; Young, Thomas K; Darby, S Barnie; Reid, Stuart D; Blake, Alexander J; Wilson, Claire; Wolowska, Joanna; McInnes, Eric J L; Schröder, Martin; Love, Jason B

2007-01-01

The syntheses, characterisation and complexation reactions of a series of binucleating Schiff-base calixpyrrole macrocycles are described. The acid-templated [2+2] condensations between meso-disubstituted diformyldipyrromethanes and o-phenylenediamines generate the Schiff-base pyrrolic macrocycles H(4)L(1) to H(4)L(6) upon basic workup. The single-crystal X-ray structures of both H(4)L(3).2 EtOH and H(4)L(6).H2O confirm that [2+2] cyclisation has occurred, with either EtOH or H2O hydrogen-bonded within the macrocyclic cleft. A series of complexation reactions generate the dipalladium [Pd2(L)] (L=L(1) to L(5)), dinickel [Ni2(L(1))] and dicopper [Cu2(L)] (L=L(1) to L(3)) complexes. All of these complexes have been structurally characterised in the solid state and are found to adopt wedged structures that are enforced by the rigidity of the aryl backbone to give a cleft reminiscent of the structures of Pacman porphyrins. The binuclear nickel complexes [Ni2(mu-OMe)2Cl2(HOMe)2(H(4)L(1))] and [Ni2(mu-OH)2Cl2(HOMe)(H(4)L(5))] have also been prepared, although in these cases the solid-state structures show that the macrocyclic ligand remains protonated at the pyrrolic nitrogen atoms, and the Ni(II) cations are therefore co-ordinated by the imine nitrogen atoms only to give an open conformation for the complex. The dicopper complex [Cu2(L(3))] was crystallised in the presence of pyridine to form the adduct [Cu2(py)(L(3))], in which, in the solid state, the pyridine ligand is bound within the binuclear molecular cleft. Reaction between H(4)L(1) and [Mn(thf){N(SiMe(3))2}2] results in clean formation of the dimanganese complex [Mn2(L(1))], which, upon crystallisation, formed the mixed-valent complex [Mn2(mu-OH)(L(1))] in which the hydroxo ligand bridges the metal centres within the molecular cleft.

[Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

Science.gov (United States)

Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

2015-01-01

In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

Pseudomonas cremoricolorata Strain ND07 Produces N-acyl Homoserine Lactones as Quorum Sensing Molecules

Directory of Open Access Journals (Sweden)

Nina Yusrina Muhamad Yunos

2014-06-01

Full Text Available Quorum sensing (QS is a bacterial cell-to-cell communication system controlling QS-mediated genes which is synchronized with the population density. The regulation of specific gene activity is dependent on the signaling molecules produced, namely N-acyl homoserine lactones (AHLs. We report here the identification and characterization of AHLs produced by bacterial strain ND07 isolated from a Malaysian fresh water sample. Molecular identification showed that strain ND07 is clustered closely to Pseudomonas cremoricolorata. Spent culture supernatant extract of P. cremoricolorata strain ND07 activated the AHL biosensor Chromobacterium violaceum CV026. Using high resolution triple quadrupole liquid chromatography-mass spectrometry, it was confirmed that P. cremoricolorata strain ND07 produced N-octanoyl-l-homoserine lactone (C8-HSL and N-decanoyl-l-homoserine lactone (C10-HSL. To the best of our knowledge, this is the first documentation on the production of C10-HSL in P. cremoricolorata strain ND07.

Evaluation of anticancer properties of a new α-methylene-δ-lactone DL-249 on two cancer cell lines

Directory of Open Access Journals (Sweden)

Pomorska Dorota K.

2017-06-01

Full Text Available The anticancer activity of a new synthetic α-methylene-δ-lactone DL-249 was reported in leukemia HL-60 and breast cancer MCF-7 cells and compared with the activity of a natural α-methylene-γ-lactone from Tanacetum parthenium, parthenolide.

Hydrolyzable tannins of tamaricaceous plants. III. Hellinoyl- and macrocyclic-type ellagitannins from Tamarix nilotica.

Science.gov (United States)

Orabi, Mohamed A A; Taniguchi, Shoko; Yoshimura, Morio; Yoshida, Takashi; Kishino, Kaori; Sakagami, Hiroshi; Hatano, Tsutomu

2010-05-28

Three new hellinoyl-type ellagitannins, nilotinins M4 (7), D7 (8), and D8 (9), and a new macrocyclic-type, nilotinin D9 (10), together with eight known tannins, hirtellins B (2), C (11), and F (12), isohirtellin C (13), tamarixinin A (3), tellimagrandins I and II, and 1,2,6-tri-O-galloyl-beta-d-glucose (14), were isolated from an aqueous acetone extract of Tamarix nilotica dried leaves. Nilotinin M4 (7) is a monomeric tannin possessing a hellinoyl moiety. The structure of 8 demonstrated replacement of one of the HHDP groups at the glucose core O-4/O-6 in ordinary dimeric tannins with a galloyl moiety at O-6. This is a new structural feature among the tamaricaceous ellagitannins. On the basis of the results, reported spectroscopic assignments for 2, 3, and the macrocyclic tannins 11-13 were revised. Unusual shifts in the NMR spectra of these macrocyclic tannins are also discussed in relation to their conformations. Several tannins isolated from T. nilotica were assessed for possible cytotoxic activity against four human tumor cell lines, and nilotinin D8 (9) and hirtellin A (1) showed high cytotoxic effects.

Uranyl-organic assemblies with the macrocyclic ligand 1, 4, 8, 11-tetra-aza-cyclo-tetradecane-1, 4, 8, 11-tetraacetate (TETA)

International Nuclear Information System (INIS)

Thuery, Pierre

2010-01-01

Three uranyl ion complexes obtained from the reaction of uranyl nitrate hexahydrate and 1, 4, 8, 11-tetra-aza-cyclo-tetradecane-1, 4, 8, 11-tetraacetic acid (H 4 TETA) were characterized by their crystal structure. The centrosymmetric macrocycle, in the [3434] conformation with either carbon or nitrogen atoms as corners, is zwitterionic, with four carboxylate groups and two or four protonated nitrogen atoms. The complexes [(UO 2 ) 2 (H 2 TETA)(C 2 O 4 )(H 2 O) 2 ] (1) and [UO 2 (H 4 TETA)(H 2 O)].NO 3 .Cl (2) were synthesized under hydrothermal conditions and 1 includes additional oxalate ligands generated in situ. Both compounds are two-dimensional polymers in which the four-fold monodentate macrocyclic ligand unites either four uranyl oxalate dinuclear species (1) or isolated uranyl ions (2). Complex 3, [UO 2 (H 2 TETA)(H 2 O)].6H 2 O, was obtained at room temperature and, although it displays the same stoichiometry as 2, it differs from it by being a three-dimensional framework. Both 2 and 3 present channels containing either counter-ions or water molecules. As often observed, the water content of the low-temperature species, 3, is higher than that of the high-temperature one, 2. (author)

Study of behaviour of Ni(III) macrocyclic complexes in acidic ...

Indian Academy of Sciences (India)

The Cu(II) ion-catalysed kinetics of oxidation of H2O2 by [NiIIIL] [where L ... The rate of the reaction of both complexes with hydrogen peroxide shows contrasting ... enhanced kinetic and thermodynamic stabilities. The redox chemistry of synthetic poly-aza macrocycles explores the properties of nickel containing enzymes.1.

Dimetal Complexes of a Bibrachial 2+2 Thiolate-based Macrocycle

DEFF Research Database (Denmark)

Lennartson, Anders; McKee, Vickie; Nelson, Jane

2012-01-01

Protocols for accessing the [2+3] and [2+2] tren + thiophenolate-based cryptands and macrocycles, respectively, have been devised; however, a propensity towards incomplete crypt formation is clear: Cd(II)2, Mn(II)2, Ni(II)2 and Pd(II)2 complexes of the [2+2] bibrachial systems in which one arm of...

Eukaryotic interference with homoserine lactone mediated procaryotic signalling

DEFF Research Database (Denmark)

Givskov, Michael Christian; de Nys, Rocky; Gram, Lone

1996-01-01

Acylated homoserine lactones (AHLs) plays a widespread role in intercellular communication among bacteria. The Australian macroalga Delisea pulchra produces secondary metabolites which have structural similarities to AHL molecules. We report here that these metabolites inhibited AHL-controlled pr......-controlled processes in prokaryotes. Our results suggest that the interaction between higher organisms and their surface-associated bacteria may be mediated by interference with bacterial regulatory systems....

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

Directory of Open Access Journals (Sweden)

Marco Caricato

2012-06-01

Full Text Available We report on the synthesis and characterization of novel shape-persistent, optically active arylamide macrocycles, which can be obtained using a one-pot methodology. Resolved, axially chiral binol scaffolds, which incorporate either methoxy or acetoxy functionalities in the 2,2' positions and carboxylic functionalities in the external 3,3' positions, were used as the source of chirality. Two of these binaphthyls are joined through amidation reactions using rigid diaryl amines of differing shapes, to give homochiral tetraamidic macrocycles. The recognition properties of these supramolecular receptors have been analyzed, and the results indicate a modulation of binding affinities towards dicarboxylate anions, with a drastic change of binding mode depending on the steric and electronic features of the functional groups in the 2,2' positions.

Production of acylated homoserine lactones by psychrotrophic members of the Enterobacteriaceae isolated from foods

DEFF Research Database (Denmark)

Gram, Lone; Christensen, A.B.; Flodgaard, Lars

1999-01-01

Bacteria are able to communicate and gene regulation can be mediated through the production of acylated homoserine lactone (AHL) signal molecules. These signals play important roles in several pathogenic and symbiotic bacteria. The following study was undertaken to investigate whether AHLs...... indicated that N-3-oxohexanoyl homoserine lactone was the major AHL of several of the strains isolated from cold-smoked salmon and meat. AHL-positive strains cultured at 5 degrees C in medium supplemented with 4% NaCl produced detectable amounts of AHL(s) at cell densities of 10(6) CFU/ml. AHLs were...

Enthalpy of vaporization and vapor pressure of whiskey lactone and menthalactone by correlation gas chromatography

International Nuclear Information System (INIS)

Simmons, Daniel; Chickos, James

2017-01-01

Highlights: • The vapor pressure and vaporization enthalpies of cis and trans-whiskey lactone have been evaluated. • Enthalpies of vaporization and vapor pressures of (+)-isomintlactone and (−)-mintlactone were also evaluated. • The sublimation enthalpy and corresponding vapor pressure of (+) -isomintlactone at T = 298.15 K is estimated. - Abstract: Enthalpies of vaporization at T = 298.15 K of cis and trans-whiskey lactone have been evaluated by correlation gas chromatography to be (68.4 ± 1.7) kJ·mol −1 and (67.5 ± 1.7) kJ·mol −1 , respectively. The enthalpies of vaporization of isomintlactone and mintlactone also evaluated by correlation gas chromatography have been found to have vaporization enthalpies of (74.2 ± 1.8) kJ·mol −1 and (73.2 ± 1.8) kJ·mol −1 respectively. The vapor pressures for cis and trans-whiskey lactone at T = 298.15 K have been evaluated as (1.5 ± 0.09) Pa and (2.0 ± 0.1) Pa using vapor pressures of a series of lactones as standards. Vapor pressures for isomintlactone and mintlactone were evaluated as (0.26 ± 0.012) Pa and (0.33 ± 0.02) Pa, respectively. Fusion and sublimation enthalpies for (+)-isomintlactone as well as the vapor pressure of the solid have been estimated.

Anthelmintic resistance in equine nematodes

Directory of Open Access Journals (Sweden)

Jacqueline B. Matthews

2014-12-01

Full Text Available Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole, tetrahydropyrimidines (pyrantel and macrocyclic lactones (ivermectin, moxidectin. Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop

Extraction of oak volatiles and ellagitannins compounds and sensory profile of wine aged with French winewoods subjected to different toasting methods: behaviour during storage.

Science.gov (United States)

Chira, Kleopatra; Teissedre, Pierre-Louis

2013-09-01

In Merlot wines the evolution of volatile and non-volatile (ellagitannins) compounds extracted from winewoods while being macerated for 12 months was studied. Seven types of winewoods subjected to different toasting methods were used. Different rates of extraction, depending mainly on wood compounds origin (toasting or naturally present in wood) and on the watering process during toasting, were observed, which were reflected in sensory differences. Globally, volatile phenols together with aldehydes, phenols and lactones showed an increase with increasing maceration time. Ellagitannins were extracted faster during the first 3 months; after 6 months an important decrease was observed. Wines with winewoods subjected to watering during toasting were lower in ellagitannins concentrations and demonstrated the greatest decrease of these compounds during maceration. Astringency and bitterness intensified with increasing ellagitannins. Lactones induced positive sweetness sensations, whereas furanic and guaiacol compounds influenced bitterness and astringency. Spicy and vanilla descriptors were related to eugenol, vanillin and other odorous chemicals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design and synthesis of macrocyclic ligands and their complexes of lanthanides and actinides

International Nuclear Information System (INIS)

Alexander, V.

1995-01-01

A review article which covers the various design and synthetic strategies developed to synthesize macrocyclic complexes of lanthanides and actinides, their structural features, quantitative studies on the stabilities of these complexes, their applications, and the structure-reactivity principle would be an asset for those who are actively engaged in this area of research. This review is also purported to give a comprehensive view of the current status of this area of research to the beginners and to highlight the application of this chemical research to emerging nonchemical applications to lure the potential workers. The coordination template effect provides a general strategy for the synthesis of a wide variety of discrete metal complexes. The principal conceptual and experimental development that have established and exploited this strategy are briefly outlined. A brief review of the coordination template effect and subsequent developments in the design of macrocyclic complexes of alkali, alkaline earth, and transition metal ions is presented as an essential basis for the rational design of new macrocyclic complexes of lanthanides and actinides. The exciting aspect of this chemistry is that in the majority of cases the molecules meet the design criteria very well. It is evident that in an increasing number of cases the driving force behind the synthetic effort is the desire to create a molecule which will enable the user to make specific applications. 506 refs

Synthesis of new 3-and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers

DEFF Research Database (Denmark)

Olsen, Jacob Alsbæk; Severinsen, Rune Eg; Rasmussen, Thomas Bovbjerg

2002-01-01

The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which...... substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system....

Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

DEFF Research Database (Denmark)

Rasmussen, Bastian Barker; Nielsen, Kristian Fog; Machado, Henrique

2014-01-01

Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the en......Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae...... violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were...

Method to produce water-soluble sugars from biomass using solvents containing lactones

Science.gov (United States)

Dumesic, James A.; Luterbacher, Jeremy S.

2017-08-08

A process to produce an aqueous solution of carbohydrates that contains C6-sugar-containing oligomers, C6 sugar monomers, C5-sugar-containing oligomers, C5 sugar monomers, or any combination thereof is presented. The process includes the steps of reacting biomass or a biomass-derived reactant with a solvent system including a lactone and water, and an acid catalyst. The reaction yields a product mixture containing water-soluble C6-sugar-containing oligomers, C6-sugar monomers, C5-sugar-containing oligomers, C5-sugar monomers, or any combination thereof. A solute is added to the product mixture to cause partitioning of the product mixture into an aqueous layer containing the carbohydrates and a substantially immiscible organic layer containing the lactone.

An eighteen-membered macrocyclic ligand for actinium-225 targeted alpha therapy

International Nuclear Information System (INIS)

Thiele, Nikki A.; MacMillan, Samantha N.; Wilson, Justin J.; Rodriguez-Rodriguez, Cristina

2017-01-01

The 18-membered macrocycle H 2 macropa was investigated for 225 Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all 225 Ac (26 kBq) in 5 min at RT. [ 225 Ac(macropa)] + remained intact over 7 to 8 days when challenged with either excess La 3+ ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa-NCS, was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. Both constructs rapidly radiolabeled 225 Ac in just minutes at RT, and macropa-Tmab retained >99 % of its 225 Ac in human serum after 7 days. In LNCaP xenograft mice, 225 Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free 225 Ac over 96 h. These findings establish macropa to be a highly promising ligand for 225 Ac chelation that will facilitate the clinical development of 225 Ac TAT for the treatment of soft-tissue metastases. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

Dinuclear Silver(I) and Copper(II) Complexes of Hexadentate Macrocyclic Ligands Containing p-Xylyl Spacers

DEFF Research Database (Denmark)

McKenzie, Christine J.; Nielsen, Lars Preuss; Søtofte, Inger

1998-01-01

The cyclocondensation of terephthalic aldehyde with N,N-bis(3-aminopropyl)-methylamine in the presence of silver(I) gives the dinuclear tetramine Schiff base macrocyclic complex, [Ag2L1](NO3)2 (L1=7,22-N,N'-dimethyl-3,7,11,18, 22,26-hexaazatricyclo[26.2.21.18.213.16]-tetratricosa-2,11,13,15,1 7......,26,28,30,31,33-decaene). [Ag2L1](NO3)2 crystallizes in the monoclinic space group P21/c, with a=14.153(6), b=12.263(4), c=9.220(2) Å, beta=97.52(3) Å and Z=2. The silver ions are strongly coordinated at each end of the macrocycle by the two imine nitrogen atoms [2.177(3) and 2.182(3) Å] with close interatomic...... interactions to an oxygen atom of a nitrate ion and an amine nitrogen atom [2.580(2) and 2.690(2) Å]. The Ag...Ag distance is 6.892(3) Å. The free tetraimine macrocycle, L1, was obtained by treatment of [Ag2L1](NO3)2 with an excess of iodide, and the reduced derivative 7,22-N,N'-dimethyl-3...

Study of the contribution of massoia lactone to the aroma of Merlot and Cabernet Sauvignon musts and wines.

Science.gov (United States)

Pons, Alexandre; Allamy, Lucile; Lavigne, Valérie; Dubourdieu, Denis; Darriet, Philippe

2017-10-01

Organic extracts of musts and red wines marked by dried fruit and cooked fruit aromas were analyzed by gas chromatography coupled to olfactometry and mass spectrometry. Thanks to this analytical approach we identified a fragrant lactone corresponding to an odorant zone reminiscent of coconut and dried figs as 5,6-dihydro-6-pentyl-2H-pyran-2-one (C10 massoia lactone). Using chiral GC-GC-MS, we show that only the (R)-C10 massoia lactone is found in musts and wines. Its detection thresholds were 10µg/L and 11µg/L in must and wine model solution, respectively. In Merlot and Cabernet Sauvignon musts marked by dried fruit flavors from overripe grapes, its concentration reached 68µg/L. In contrast, in wines marked by these flavors, it never exceeded 20µg/L. We show that (R)-C10 massoia lactone is reduced to (R)-δ-decalactone during alcoholic fermentation. In addition, we underline the contribution of temperature during the growing season on its level in old red wines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and evaluation of antimicrobial activity of halogenated furans and analogue compounds to nostoclides; Sintese e avaliacao da atividade antimicrobiana de furanonas halogenadas e de compostos analogos aos nostoclideos

Energy Technology Data Exchange (ETDEWEB)

Barbosa, Luiz C.A.; Maltha, Celia R.A.; Demuner, Antonio J.; Pinheiro, Patricia F.; Varejao, Jodieh O.S.; Montanari, Ricardo M., E-mail: lcab@ufv.b [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica; Andrade, Nelio J. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Ciencia e Tecnologia de Alimentos

2010-07-01

Considering the broad spectrum of biological activity of gamma-butyrolactone derivatives, we presented the synthesis of 3,4-dihalo-5-arylidenefuran-2(5H)-ones (17-21) and analogues (24-28) of the natural product nostoclide (7,8). Furanones 17-21 were synthesized from the condensation of aromatic aldehydes with lactones 14 and 15, that were obtained from mucobromic and mucochloric acids. Lactone 15 was converted into the intermediate 23 in 36% overall yield. Compound 23 was then transformed into the nostoclide analogues 24-28. Some of the compounds prepared showed antimicrobial activities against Escherichia coli, Staphylococcus aureus and Bacillus cereus comparable to commercial antibiotics. (author)

Peptide Macrocycles Featuring a Backbone Secondary Amine: A Convenient Strategy for the Synthesis of Lipidated Cyclic and Bicyclic Peptides on Solid Support

DEFF Research Database (Denmark)

Oddo, Alberto; Münzker, Lena; Hansen, Paul Robert

2015-01-01

A convenient strategy for the on-resin synthesis of macrocyclic peptides (3- to 13-mers) via intramolecular halide substitution by a diamino acid is described. The method is compatible with standard Fmoc/tBu SPPS and affords a tail-to-side-chain macrocyclic peptide featuring an endocyclic secondary...

A comparative study of aroma-active compounds between dark and milk chocolate: relationship to sensory perception.

Science.gov (United States)

Liu, Jianbin; Liu, Mengya; He, Congcong; Song, Huanlu; Guo, Jia; Wang, Ye; Yang, Haiying; Su, Xiaoxia

2015-04-01

The most important aroma-active compounds of two types of chocolate and cocoa liquor used for their production were analysed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS) and aroma extract dilution analysis (AEDA). Furthermore, the relationship between odorants and sensory perception of chocolate was measured by quantitative analysis, sensory evaluation and correlation analysis. In addition, some chemicals were added to the original dark or milk chocolate to validate their roles in the aroma property of chocolate. A total of 32 major aroma-active compounds were identified in the chocolate with the flavour dilution factors of 27-729 by AEDA, including seven aldehydes, six pyrazines, three pyrroles, four carboxylic acids, four lactones, two alcohols, two ketones, one ester, one pyrone, one furan and one sulfur-containing compound. Further quantitative analysis showed that dark chocolate had higher contents of pyrazine, pyrrole, carboxylic acids, alcohols and Strecker aldehydes, whereas the concentration of lactones, esters, long chain aldehydes and ketones were higher in the milk type. Differences in volatile composition and descriptive flavour attributes between the dark and milk chocolate were observed. The relationship between aroma-active compounds and sensory perception in the chocolate was verified. © 2014 Society of Chemical Industry.

Fabrication of reduced graphene oxide/macrocyclic cobalt complex nanocomposites as counter electrodes for Pt-free dye-sensitized solar cells

Science.gov (United States)

Tsai, Chih-Hung; Shih, Chun-Jyun; Wang, Wun-Shiuan; Chi, Wen-Feng; Huang, Wei-Chih; Hu, Yu-Chung; Yu, Yuan-Hsiang

2018-03-01

In this study, macrocyclic Co complexes were successfully grafted onto graphene oxide (GO) to produce GO/Co nanocomposites with a large surface area, high electrical conductivity, and excellent catalytic properties. The novel GO/Co nanocomposites were applied as counter electrodes for Pt-free dye-sensitized solar cells (DSSCs). Various ratios of macrocyclic Co complexes were used as the reductant to react with the GO, with which the surface functional groups of the GO were reduced and the macrocyclic ligand of the Co complexes underwent oxidative dehydrogenation, after which the conjugated macrocyclic Co systems were grafted onto the surface of the reduced GO to form GO/Co nanocomposites. The surface morphology, material structure, and composition of the GO/Co composites and their influences on the power-conversion efficiency of DSSC devices were comprehensively investigated. The results showed that the GO/Co (1:10) counter electrode (CE) exhibited an optimal power conversion efficiency of 7.48%, which was higher than that of the Pt CE. The GO/Co (1:10) CE exhibited superior electric conductivity, catalytic capacity, and redox capacity. Because GO/Co (1:10) CEs are more efficient and cheaper than Pt CEs, they could potentially be used as a replacement for Pt electrodes.

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilylmethylaniline with cyclic α,β-unsaturated carbonyl compounds

Directory of Open Access Journals (Sweden)

Dominik Lenhart

2014-04-01

Full Text Available N-Methyl-N-((trimethylsilylmethylaniline was employed as reagent in visible-light-induced, iridium-catalyzed addition reactions to cyclic α,β-unsaturated carbonyl compounds. Typical reaction conditions included the use of one equivalent of the reaction substrate, 1.5 equivalents of the aniline and 2.5 mol % (in MeOH or 1.0 mol % (in CH2Cl2 [Ir(ppy2(dtbbpy]BF4 as the catalyst. Two major reaction products were obtained in combined yields of 30–67%. One product resulted from aminomethyl radical addition, the other product was a tricyclic compound, which is likely formed by attack of the intermediately formed α-carbonyl radical at the phenyl ring. For five-membered α,β-unsaturated lactone and lactam substrates, the latter products were the only products isolated. For the six-membered lactones and lactams and for cyclopentenone the simple addition products prevailed.

Cyclooctane metathesis catalyzed by silica-supported tungsten pentamethyl [(ΞSiO)W(Me)5]: Distribution of macrocyclic alkanes

KAUST Repository

Riache, Nassima

2014-10-03

Metathesis of cyclic alkanes catalyzed by the new surface complex [(ΞSiO)W(Me)5] affords a wide distribution of cyclic and macrocyclic alkanes. The major products with the formula CnH2n are the result of either a ring contraction or ring expansion of cyclooctane leading to lower unsubstituted cyclic alkanes (5≤n≤7) and to an unprecedented distribution of unsubstituted macrocyclic alkanes (12≤n≤40), respectively, identified by GC/MS and by NMR spectroscopies.

Aromaticine, a sesquiterpene lactone from Amblyopappus pusillus

Directory of Open Access Journals (Sweden)

Matías López-Rodríguez

2008-02-01

Full Text Available Aromaticine (systematic name: 4a,8-dimethyl-3-methylene-3,3a,4,4a,7a,8,9,9a-octahydroazuleno[6,5-b]furan-2,5-dione, C15H18O3, is a natural lactone isolated from Amblyopappus pusillus. The molecular structure and conformation agree with the results of Romo, Joseph-Nathan & Díaz [(1964. Tetrahedron, 20, 79–85]. The fused-ring system contains a seven-membered ring in a twist-boat conformation and two five-membered rings trans fused in envelope conformations.

Spectrophotometric determination of total lactones in Andrographis paniculata Nees

Directory of Open Access Journals (Sweden)

Napaporn Jantakun

2005-11-01

Full Text Available A spectrophotometric method for determination of total lactones in Andrographis paniculata was established by using dinitrobenzoic acid and potassium hydroxide solutions as colour forming agents. The absorbance of the solution was determined at 536 nm. The linearity range was 12-72 × 10-6 g.ml-1. The detection limit was 1.2 μg, the quantitation limit was 4.23 μg. The intraday variation had an average of slope 6082.97 g.ml-1, % RSD 0.10; an average intercept 0.2786, %RSD 3.66 (n=3. The interday variation had an average of 6146 g.ml-1 with the %RSD of 6.30 and an average intercept 0.2628, %RSD 4.95 (n=4. The coefficients of determination were 0.998-0.999. The total lactones content, calculated as andrographolide, determined by this method was 8.61±0.52% (n=4 and by the official method, Thai Herbal Pharmacopoeia, was 8.12±0.34% (n=2. The results of the two methods do not differ significantly at P=0.05 (P(|t|>0.903 = 0.53

In Planta Biocontrol of Pectobacterium atrosepticum by Rhodococcus erythropolis Involves Silencing of Pathogen Communication by the Rhodococcal Gamma-Lactone Catabolic Pathway.

Directory of Open Access Journals (Sweden)

Corinne Barbey

Full Text Available The virulence of numerous Gram-negative bacteria is under the control of a quorum sensing process based on synthesis and perception of N-acyl homoserine lactones. Rhodococcus erythropolis, a Gram-positive bacterium, has recently been proposed as a biocontrol agent for plant protection against soft-rot bacteria, including Pectobacterium. Here, we show that the γ-lactone catabolic pathway of R. erythropolis disrupts Pectobacterium communication and prevents plant soft-rot. We report the first characterization and demonstration of N-acyl homoserine lactone quenching in planta. In particular, we describe the transcription of the R. erythropolis lactonase gene, encoding the key enzyme of this pathway, and the subsequent lactone breakdown. The role of this catabolic pathway in biocontrol activity was confirmed by deletion of the lactonase gene from R. erythropolis and also its heterologous expression in Escherichia coli. The γ-lactone catabolic pathway is induced by pathogen communication rather than by pathogen invasion. This is thus a novel and unusual biocontrol pathway, differing from those previously described as protecting plants from phytopathogens. These findings also suggest the existence of an additional pathway contributing to plant protection.

EFSA ; Scientific Opinion on Flavouring Group Evaluation 98 (FGE.98): Consideration of three ring-unsaturated delta-lactones)

DEFF Research Database (Denmark)

Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present consideration concerns a group of three unsaturated delta-lactones [FL-no: 10.031, 10.037 and 10.044] previously evaluated by the JECFA at their 49th meeting in 1997. The JECFA considered that further information...... on the metabolism of these three substances was required and that they should be evaluated together with other substances containing alpha,beta-unsaturation and that, therefore, their evaluation should be deferred. However, the EFSA Panel has considered that these three JECFA evaluated aliphatic lactones can...... be hydrolysed and metabolised to innocuous products in line with the aliphatic lactones evaluated by EFSA in FGE.10Rev2. The substances were evaluated through a stepwise approach that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern...

Two new diterpenoid lactones isolated from Andrographis paniculata.

Science.gov (United States)

Wang, Gui-Yang; Wen, Ting; Liu, Fei-Fei; Tian, Hai-Yan; Chun-Lin, Fan; Huang, Xiao-Jun; Ye, Wen-Cai; Wang, Ying

2017-06-01

In the present study, two new diterpenoid lactones, 3-deoxy-andrographoside (1) and 14-deoxy-15-methoxy-andrographolide (2), were isolated from the aerial parts of Andrographis paniculata. Their structures were elucidated by combination of NMR, MS, and chemical methods. The configurations of 1 and 2 were established based on the analysis of ROESY data and single crystal X-ray diffraction experiment. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Arylation of beta, gamma-unsaturated lactones by a Heck-Matsuda reaction: an unexpected route to aryldiazene butenolides and pyridazinones

Energy Technology Data Exchange (ETDEWEB)

Taylor, Jason G.; Correia, Carlos Roque D., E-mail: roque@iqm.unicamp.b [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica

2010-07-01

The palladium catalysed coupling of aryldiazonium salts with {beta}-{gamma}-unsaturated lactones under basic conditions has been investigated. Both (3H)-furanone and {alpha}-angelicalactone were evaluated as substrates in the Heck Matsuda reaction but both failed to afford the desired arylated butenolides. Under basic conditions, {beta}-{gamma}-unsaturated lactones generate highly nucleophilic enolates that preferentially undergo azo coupling reactions with arenediazonium salts to afford aryldiazene butenolides. The electronic and steric effect of the substituents on the aryldiazonium salt in the azo coupling reaction is described. Aryldiazene-lactone derivatives were obtained in good yields from a highly facile and straightforward procedure. An aminoisomaleimide was formed from (3H)-furanone and cyclized to the corresponding pyridazinones in modest yield. (author)

Macrocyclic extractants for separating Am(III)/Ln(III)

International Nuclear Information System (INIS)

Ludwig, R.; Nguyen, T.K.D.; Kunogi, K.; Tachimori, Shoichi

1999-01-01

The extraction of trivalent f-elements by calix(n)arene-type macrocyclic ligands increases in the order n=4, 8, 6 corresponding to the balance between cavity size, molecular flexibility, and number of donor atoms. Introduction of mixed functionalities into calix(6)arenes, e.g. carboxylic acid and amide groups, results in better extractability of actinides compared with lanthanides. For calix(4)arenes, such a different extractability could not be observed. Furthermore, the effects of solvent composition with respect to a modifier and of the aqueous phase composition were investigated. (author)

“One Ring to Bind Them All”—Part I: The Efficiency of the Macrocyclic Scaffold for G-Quadruplex DNA Recognition

Directory of Open Access Journals (Sweden)

David Monchaud

2010-01-01

Full Text Available Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the “standard” B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes, and in addressing both synthetic issues and biological aspects.

Sceliphrolactam, a polyene macrocyclic lactam from a wasp-associated Streptomyces sp

DEFF Research Database (Denmark)

Oh, Dong-Chan; Poulsen, Michael; Currie, Cameron R

2011-01-01

A previously unreported 26-membered polyene macrocyclic lactam, sceliphrolactam, was isolated from an actinomycete, Streptomyces sp., associated with the mud dauber, Sceliphron caementarium. Sceliphrolactam's structure was determined by 1D- and 2D-NMR, MS, UV, and IR spectral analysis. Sceliphrol...

Complexation of Eu3+ with a macrocyclic lactam receptor: Experimental and theoretical study

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Záliš, Stanislav; Sedláková, Zdeňka; Vaňura, P.

2013-01-01

Roč. 1038, APR 2013 (2013), s. 216-219 ISSN 0022-2860 Institutional support: RVO:61388955 ; RVO:61389013 Keywords : europium * macrocyclic lactam receptor * complexation Subject RIV: CF - Physical ; Theoretical Chemistry; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 1.599, year: 2013

Complexation of the strontium cation with a macrocyclic lactam receptor: Experimental and theoretical study

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Záliš, Stanislav; Vaňura, P.

2016-01-01

Roč. 214, FEB 2016 (2016), s. 171-174 ISSN 0167-7322 Institutional support: RVO:61388955 Keywords : strontium cation * macrocyclic lactam receptor Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.648, year: 2016

Synthesis and antiproliferative activity of some A- and B modified D-homo lactone androstane derivatives

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Savić Marina P.

2013-01-01

Full Text Available An efficient synthesis of several A- and B-modified D-homo lactone androstane derivatives from 3β-hydroxy-17-oxa-D-homoandrost-5-en-16-one (1 is reported. 17-Oxa-Dhomoandrost- 4-ene-3,16-dione (2, obtained by the Oppenauer oxidation of compound 1, was converted via the unstable intermediate 3,16-dioxo-4,17-dioxa-D-homoandrostane- 5α-carboxaldehyde (3 to 17-oxa-D-homo-3,5-seco-4-norandrostan-5-one-3-carboxylic acid (4, which was also obtained directly from compound 2. Compound 1 was acetylated to give 17-oxa-D-homoandrost-5-en-16-on-3β-yl acetate (5 which was then oxidized with chromium(VI-oxide in 50% acetic acid or with meta-chlorperbenzoic acid and chromium(VI-oxide to yield compounds 6-8 and 5α-hydroxy-17-oxa-D-homoandrostane- 6,16-dion-3β-yl acetate (9, respectively. The oximination of compound 9 gave a mixture of 6(E-hydroximino-5α-hydroxy-17-oxa-D-homoandrostan-16-on-3β-yl acetate (10 and 6(Z-hydroximino-5α-hydroxy-17-oxa-D-homoandrostan-16-on-3β-yl acetate (11, the hydrolysis of which gave 6(E-hydroximino-3β,5α-dihydroxy-17-oxa-D-homoandrostan- 16-one (12 and 6(Z-hydroximino-3β,5α-dihydroxy-17-oxa-D-homoandrostan-16-one (13. 6-Nitrile-17-oxa-5,6-seco-D-homoandrostane-5,16-dion-3β-yl acetate (14 was obtained under the Beckmann fragmentation of compounds 10 and 11. Only pure and stable compounds (1, 2, 4, 5, 9 and 14 were tested in vitro on six malignant cell lines (MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, K562 and one non-tumor MRC-5 cell line. Significant antiproliferative activity against MDA-MB-231 cells showed compounds 1, 5 and 9, while compound 2 exhibited a strong antiproliferative activity. Only compound 14 showed weak antiproliferative activity against MCF-7 cells. All tested compounds were not toxic on MRC-5 cells, whereas Doxorubicin was highly toxic on these cells. [Projekat Ministarstva nauke Republike Srbije, br. 172021

Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles.

Science.gov (United States)

Pylina, Yana I; Shadrin, Dmitry M; Shevchenko, Oksana G; Startseva, Olga M; Velegzhaninov, Igor O; Belykh, Dmitry V; Velegzhaninov, Ilya O

2017-01-05

In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series-pyropheophorbide-a 17-diethylene glycol ester (Compound 21 ) was performed. This new compound is characterized by lower dark cytotoxicity and higher photoinduced cytotoxicity than previously described in a similar compound (DH-I-180-3) and clinically used Photolon TM . Using fluorescent microscopy, it was shown that Compound 21 quickly penetrates the cells. Analysis of caspase-3 activity indicated an apoptosis induction 40 min after exposure to red light (λ = 660 nm). The induction of DNA damages and apoptosis was shown using Comet assay. The results of expression analysis of the stress-response genes indicate an activation of the genes which control the cell cycle and detoxification of the free radicals after an exposure of HeLa cells to Compound 21 and to red light. High photodynamic activity of this compound and the ability to oxidize biomolecules was demonstrated on nuclear-free mice erythrocytes. In addition, it was shown that Compound 21 is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound 21 is a prospective substance for development of the new drugs for photodynamic therapy of cancer.

Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles

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Yana I. Pylina

2017-01-01

Full Text Available In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series—pyropheophorbide-a 17-diethylene glycol ester (Compound 21 was performed. This new compound is characterized by lower dark cytotoxicity and higher photoinduced cytotoxicity than previously described in a similar compound (DH-I-180-3 and clinically used PhotolonTM. Using fluorescent microscopy, it was shown that Compound 21 quickly penetrates the cells. Analysis of caspase-3 activity indicated an apoptosis induction 40 min after exposure to red light (λ = 660 nm. The induction of DNA damages and apoptosis was shown using Comet assay. The results of expression analysis of the stress-response genes indicate an activation of the genes which control the cell cycle and detoxification of the free radicals after an exposure of HeLa cells to Compound 21 and to red light. High photodynamic activity of this compound and the ability to oxidize biomolecules was demonstrated on nuclear-free mice erythrocytes. In addition, it was shown that Compound 21 is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound 21 is a prospective substance for development of the new drugs for photodynamic therapy of cancer.

Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

Energy Technology Data Exchange (ETDEWEB)

Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)

2017-06-06

We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

Isolation and characterization of 9-lipoxygenase and epoxide hydrolase 2 genes: Insight into lactone biosynthesis in mango fruit (Mangifera indica L.).

Science.gov (United States)

Deshpande, Ashish B; Chidley, Hemangi G; Oak, Pranjali S; Pujari, Keshav H; Giri, Ashok P; Gupta, Vidya S

2017-06-01

Uniqueness and diversity of mango flavour across various cultivars are well known. Among various flavour metabolites lactones form an important class of aroma volatiles in certain mango varieties due to their ripening specific appearance and lower odour detection threshold. In spite of their biological and biochemical importance, lactone biosynthetic pathway in plants remains elusive. Present study encompasses quantitative real-time analysis of 9-lipoxygenase (Mi9LOX), epoxide hydrolase 2 (MiEH2), peroxygenase, hydroperoxide lyase and acyl-CoA-oxidase genes during various developmental and ripening stages in fruit of Alphonso, Pairi and Kent cultivars with high, low and no lactone content and explains their variable lactone content. Study also covers isolation, recombinant protein characterization and transient over-expression of Mi9LOX and MiEH2 genes in mango fruits. Recombinant Mi9LOX utilized linoleic and linolenic acids, while MiEH2 utilized aromatic and fatty acid epoxides as their respective substrates depicting their role in fatty acid metabolism. Significant increase in concentration of δ-valerolactone and δ-decalactone upon Mi9LOX over-expression and that of δ-valerolactone, γ-hexalactone and δ-hexalactone upon MiEH2 over-expression further suggested probable involvement of these genes in lactone biosynthesis in mango. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities

DEFF Research Database (Denmark)

Kitir, Betül; Maolanon, Alex R.; Ohm, Ragnhild G.

2017-01-01

medicines. Therefore, detailed mechanistic information and precise characterization of the chemical probes used to investigate the effects of HDAC enzymes are vital. We interrogated Nature's arsenal of macrocyclic nonribosomal peptide HDAC inhibitors by chemical synthesis and evaluation of more than 30...... natural products and analogues. This furnished surprising trends in binding affinities for the various macrocycles, which were then exploited for the design of highly potent class I and IIb HDAC inhibitors. Furthermore, thorough kinetic investigation revealed unexpected inhibitory mechanisms of important...

Physical Removal of Anions from Aqueous Media by Means of a Macrocycle-Containing Polymeric Network

KAUST Repository

Ji, Xiaofan

2018-02-13

Reported here is a hydrogel-forming polymer network that contains a water-soluble tetracationic macrocycle. Upon immersion of this polymer network in aqueous solutions containing various inorganic and organic salts, changes in the physical properties are observed that are consistent with absorption of the constituent anions into the polymer network. This absorption is ascribed to host-guest interactions involving the tetracationic macrocyclic receptor. Removal of the anions may then be achieved by lifting the resulting hydrogels out of the aqueous phase. Treating the anion-containing hydrogels with dilute HCl leads to the protonation-induced release of the bound anions. This allows the hydrogels to be recycled for reuse. The present polymer network thus provides a potentially attractive approach to removing undesired anions from aqueous environments.

Antifouling Compounds from Marine Macroalgae.

Science.gov (United States)

Dahms, Hans Uwe; Dobretsov, Sergey

2017-08-28

Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of biogenic compounds and the determination of their structure could provide leads for the development of environmentally-friendly antifouling paints. Isolated substances with potent antifouling activity belong to fatty acids, lipopeptides, amides, alkaloids, lactones, steroids, terpenoids, and pyrroles. It is unclear as yet to what extent symbiotic microorganisms are involved in the synthesis of these compounds. Algal secondary metabolites have the potential to be produced commercially using genetic and metabolic engineering techniques. This review provides an overview of publications from 2010 to February 2017 about antifouling activity of green, brown, and red algae. Some researchers were focusing on antifouling compounds of brown macroalgae, while metabolites of green algae received less attention. Several studies tested antifouling activity against bacteria, microalgae and invertebrates, but in only a few studies was the quorum sensing inhibitory activity of marine macroalgae tested. Rarely, antifouling compounds from macroalgae were isolated and tested in an ecologically-relevant way.

An eighteen-membered macrocyclic ligand for actinium-225 targeted alpha therapy

Energy Technology Data Exchange (ETDEWEB)

Thiele, Nikki A.; MacMillan, Samantha N.; Wilson, Justin J. [Cornell Univ., Ithaca, NY (United States). Chemistry and Chemical Biology; Brown, Victoria; Jermilova, Una; Ramogida, Caterina F.; Robertson, Andrew K.H.; Schaffer, Paul; Radchenko, Valery [TRIUMF, Vancouver, BC (Canada). Life Science Div.; Kelly, James M.; Amor-Coarasa, Alejandro; Nikolopoulou, Anastasia; Ponnala, Shashikanth; Williams, Clarence Jr.; Babich, John W. [Radiology, Weill Cornell Medicine, New York, NY (United States); Rodriguez-Rodriguez, Cristina [British Columbia Univ., Vancouver, BC (Canada). Dept. of Physics and Astronomy and Centre for Comparative Medicine

2017-11-13

The 18-membered macrocycle H{sub 2}macropa was investigated for {sup 225}Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all {sup 225}Ac (26 kBq) in 5 min at RT. [{sup 225}Ac(macropa)]{sup +} remained intact over 7 to 8 days when challenged with either excess La{sup 3+} ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa-NCS, was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. Both constructs rapidly radiolabeled {sup 225}Ac in just minutes at RT, and macropa-Tmab retained >99 % of its {sup 225}Ac in human serum after 7 days. In LNCaP xenograft mice, {sup 225}Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free {sup 225}Ac over 96 h. These findings establish macropa to be a highly promising ligand for {sup 225}Ac chelation that will facilitate the clinical development of {sup 225}Ac TAT for the treatment of soft-tissue metastases. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

Investigation of the potential of silica-bonded macrocyclic ligands for separation of metal ions from nuclear waste

International Nuclear Information System (INIS)

Camaioni, D.M.; Colton, N.G.; Bruening, R.L.

1992-01-01

This report describes the testing of some novel separations materials known as SuperLig trademark materials for their ability to separate efficiently and selectively certain metal ions from a synthetic, nonradioactive nuclear waste solution. The materials, developed and patented by IBC Advanced Technologies, are highly selective macrocyclic ligands that have been covalently bonded to silica gel. The SuperLig trademark materials that were tested are: (1) SuperLig trademark 601 for barium (Ba 2+ ) and strontium (Sr 2+ ) separation, (2) SuperLig trademark 602 for cesium (Cs + ) and rubidium (Rb + ) separation, (3) SuperLig trademark 27 for palladium (Pd 2+ ) separation, and (4) SuperLig trademark II for silver (Ag + ) and ruthenium (Ru 3+ ) separation. Our observations show that the technology for separating metal ions using silica-bonded macrocycles is essentially sound and workable to varying degrees of success that mainly depend on the affinity of the macrocycle for the metal ion of interest. It is expected that ligands will be discovered or synthesized that are amenable to separating metal ions of interest using this technology. Certainly more development, testing, and evaluation is warranted. 3 figs., 11 tabs

Sesquiterpene lactone dermatitis in the young: is atopy a risk factor?

DEFF Research Database (Denmark)

Paulsen, Evy; Otkjaer, Aksel; Andersen, Klaus E

2008-01-01

was to present another 2 cases in children and review the literature. Screening with sesquiterpene lactone (SL) mix has shown prevalence of 0.5% and 1.8% in 2 studies, while screening with 2 different Compositae mixes detected 4.2% and 2.6% positives among children and adolescents. All individual case reports...

Experimental and DFT study on complexation of Eu3+ with a macrocyclic lactam receptor

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Záliš, Stanislav; Vaňura, P.; Sedláková, Zdeňka

2013-01-01

Roč. 24, č. 6 (2013), s. 2149-2153 ISSN 1040-0400 Institutional support: RVO:61388955 ; RVO:61389013 Keywords : europium * macrocyclic lactam receptor * complexation Subject RIV: CF - Physical ; Theoretical Chemistry; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 1.900, year: 2013

Synthesis of 5α-Androstane-17-spiro-δ-lactones with a 3-Keto, 3-Hydroxy, 3-Spirocarbamate or 3-Spiromorpholinone as Inhibitors of 17β-Hydroxysteroid Dehydrogenases

Directory of Open Access Journals (Sweden)

Donald Poirier

2013-01-01

Full Text Available We synthesized two series of androstane derivatives as inhibitors of type 3 and type 5 17β-hydroxysteroid dehydrogenases (17β-HSDs. In the first series, four monospiro derivatives at position C17 were prepared from androsterone (ADT or epi-ADT. After the protection of the alcohol at C3, the C17-ketone was alkylated with the lithium acetylide of tetrahydro-2-(but-3-ynyl-2-H-pyran, the triple bond was hydrogenated, the protecting groups hydrolysed and the alcohols oxidized to give the corresponding 3-keto-17-spiro-lactone derivative. The other three compounds were generated from this keto-lactone by reducing the ketone at C3, or by introducing one or two methyl groups. In the second series, two dispiro derivatives at C3 and C17 were prepared from epi-ADT. After introducing a spiro-δ-lactone at C17 and an oxirane at C3, an aminolysis of the oxirane with L-isoleucine methyl ester provided an amino alcohol, which was treated with triphosgene or sodium methylate to afford a carbamate- or a morpholinone-androstane derivative, respectively. These steroid derivatives inhibited 17β-HSD3 (14–88% at 1 μM; 46–94% at 10 μM and 17β-HSD5 (54–73% at 0.3 μM; 91–92% at 3 μM. They did not produce any androgenic activity and did not bind steroid (androgen, estrogen, glucocorticoid and progestin receptors, suggesting a good profile for prostate cancer therapy.

Nonbioluminescent strains of Photobacterium phosphoreum produce the cell-to-cell communication signal N-(3-Hydroxyoctanoyl)homoserine lactone

DEFF Research Database (Denmark)

Flodgaard, Lars; Dalgaard, Paw; Andersen, Jens Bo

2005-01-01

Bioluminescence is a common phenotype in marine bacteria, such As Vibrio and Photobacterium species, and can be quorum regulated by N-acylated homoserine lactones (AHLs). We extracted a molecule that induced a bacterial AHL monitor (Agrobacterium tumefaciens NT1 [pZLR4]) from packed cod fillets......) and shape to N-(3-hydroxyoctanoyl)homoserine lactone, and the presence of this molecule in culture supernatants from a nonbioluminescent strain of P. phosphoreum was confirmed by high-performance liquid chromatography-positive electrospray high-resolution mass spectrometry. Bioluminescence (in a non...

Physical Removal of Anions from Aqueous Media by Means of a Macrocycle-Containing Polymeric Network

KAUST Repository

Ji, Xiaofan; Wu, Ren-Tsung; Long, Lingliang; Guo, Chenxing; Khashab, Niveen M.; Huang, Feihe; Sessler, Jonathan L.

2018-01-01

Reported here is a hydrogel-forming polymer network that contains a water-soluble tetracationic macrocycle. Upon immersion of this polymer network in aqueous solutions containing various inorganic and organic salts, changes in the physical

Sesquiterpene lactone trilobolide activates production of interferon-γ and nitric oxide

Czech Academy of Sciences Publication Activity Database

Kmoníčková, Eva; Harmatha, Juraj; Vokáč, Karel; Kostecká, Petra; Farghali, H.; Zídek, Zdeněk

2010-01-01

Roč. 81, č. 8 (2010), s. 1213-1219 ISSN 0367-326X R&D Projects: GA ČR GA305/07/0061 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40550506 Keywords : trilobolide * nitric oxide * sesquiterpene lactones Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.899, year: 2010

Heliolactone, a non-sesquiterpene lactone germination stimulant for root parasitic weeds from sunflower.

Science.gov (United States)

Ueno, Kotomi; Furumoto, Toshio; Umeda, Shuhei; Mizutani, Masaharu; Takikawa, Hirosato; Batchvarova, Rossitza; Sugimoto, Yukihiro

2014-12-01

Root exudates of sunflower (Helianthus annuus L.) line 2607A induced germination of seeds of root parasitic weeds Striga hermonthica, Orobanche cumana, Orobanche minor, Orobanche crenata, and Phelipanche aegyptiaca. Bioassay-guided purification led to the isolation of a germination stimulant designated as heliolactone. FT-MS analysis indicated a molecular formula of C20H24O6. Detailed NMR spectroscopic studies established a methylfuranone group, a common structural component of strigolactones connected to a methyl ester of a C14 carboxylic acid via an enol ether bridge. The cyclohexenone ring is identical to that of 3-oxo-α-ionol and the other part of the molecule corresponds to an oxidized carlactone at C-19. It is a carlactone-type molecule and functions as a germination stimulant for seeds of root parasitic weeds. Heliolactone induced seed germination of the above mentioned root parasitic weeds, while dehydrocostus lactone and costunolide, sesquiterpene lactones isolated from sunflower root exudates, were effective only on O. cumana and O. minor. Heliolactone production in aquacultures increased when sunflower seedlings were grown hydroponically in tap water and decreased on supplementation of the culture with either phosphorus or nitrogen. Costunolide, on the other hand, was detected at a higher concentration in well-nourished medium as opposed to nutrient-deficient media, thus suggesting a contrasting contribution of heliolactone and the sesquiterpene lactone to the germination of O. cumana under different soil fertility levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intercalation compounds involving inorganic layered structures

Directory of Open Access Journals (Sweden)

CONSTANTINO VERA R. L.

2000-01-01

Full Text Available Two-dimensional inorganic networks can shown intracrystalline reactivity, i.e., simple ions, large species as Keggin ions, organic species, coordination compounds or organometallics can be incorporated in the interlayer region. The host-guest interaction usually causes changes in their chemical, catalytic, electronic and optical properties. The isolation of materials with interesting properties and making use of soft chemistry routes have given rise the possibility of industrial and technological applications of these compounds. We have been using several synthetic approaches to intercalate porphyrins and phthalocyanines into inorganic materials: smectite clays, layered double hydroxides and layered niobates. The isolated materials have been characterized by elemental and thermal analysis, X-ray diffraction, surface area measurements, scanning electronic microscopy, electronic and resonance Raman spectroscopies and EPR. The degree of layer stacking and the charge density of the matrices as well their acid-base nature were considered in our studies on the interaction between the macrocycles and inorganic hosts.

Vapor pressures and enthalpies of vaporization of a series of γ and δ-lactones by correlation gas chromatography

International Nuclear Information System (INIS)

Kozlovskiy, Mikhail; Gobble, Chase; Chickos, James

2014-01-01

Highlights: • The vaporization enthalpies of γ-octanolactone, γ- and δ-undecanolactone and γ and δ-dodecanolactone are reported. • Equations for predicting the vapor pressures over the temperature range T = (298.15 to 350) K are provided. • Vaporization enthalpies are compared to predicted values. - Abstract: The vaporization enthalpies of γ-octanolactone, γ- and δ-undecanolactone and γ and δ-dodecanolactone used commercially as flavor ingredients are reported as are their vapor pressures over the temperature range T = (298.15 to 350) K. Vaporization enthalpies at T = 298.15 K of: (66.0 ± 3.9), (79.4 ± 4.4), (80.1 ± 4.5), (83.9 ± 4.6), and (84.61 ± 4.7) kJ · mol −1 and vapor pressures also at T = 298.15 K of: (2.8 ± 0.9), (0.12 ± 0.05), (0.09 ± 0.04), (0.04 ± 0.02), and (0.03 ± 0.02) Pa, respectively, have been evaluated by correlation gas chromatography experiments. The vaporization enthalpies of the lactones studied are reproduced within ±0.5 kJ · mol −1 using a group additivity scheme reported previously for γ- and δ-lactones. The vaporization enthalpies of the γ- and δ-lactones are compared to a similar series of ω-lactones

Systemic responses of barley to the 3-hydroxy-decanoyl-homoserine lactone producing plant beneficial endophyte Acidovorax radicis N35

Directory of Open Access Journals (Sweden)

Shengcai Han

2016-12-01

Full Text Available Quorum sensing auto-inducers of the N-acyl homoserine lactone (AHL type produced by Gram-negative bacteria have different effects on plants including stimulation on root growth and/or priming or acquirement of systemic resistance in plants. In this communication the influence of AHL production of the plant growth promoting endophytic rhizosphere bacterium Acidovorax radicis N35 on barley seedlings was investigated. A. radicis N35 produces 3-hydroxy-C10-homoserine lactone (3-OH-C10-HSL as the major AHL compound. To study the influence of this QS autoinducer on the interaction with barley, the araI-biosynthesis gene was deleted. The comparison of inoculation effects of the A. radicis N35 wild type and the araI mutant resulted in remarkable differences. While the N35 wild type colonized plant roots effectively in microcolonies, the araI mutant occurred at the root surface as single cells. Furthermore, in a mixed inoculum the wild type was much more prevalent in colonization than the araI mutant documenting that the araI mutation affected root colonization. Nevertheless, a significant plant growth promoting effect could be shown after inoculation of barley with the wild type and the araI mutant in soil after two months cultivation. While A. radicis N35 wild type showed only a very weak induction of early defense responses in plant RNA expression analysis, the araI mutant caused increased expression of flavonoid biosynthesis genes. This was corroborated by the accumulation of several flavonoid compounds such as saponarin and lutonarin in leaves of root inoculated barley seedlings. Thus, although the exact role of the flavonoids in this plant response is not clear yet, it can be concluded, that the synthesis of AHLs by A. radicis has implications on the perception by the host plant barley and thereby contributes to the establishment and function of the bacteria-plant interaction.

Asymmetric Synthesis of Apratoxin E.

Science.gov (United States)

Mao, Zhuo-Ya; Si, Chang-Mei; Liu, Yi-Wen; Dong, Han-Qing; Wei, Bang-Guo; Lin, Guo-Qiang

2016-10-21

An efficient method for asymmetric synthesis of apratoxin E 2 is described in this report. The chiral lactone 8, recycled from the degradation of saponin glycosides, was utilized to prepare the non-peptide fragment 6. In addition to this "from nature to nature" strategy, olefin cross-metathesis (CM) was applied as an alternative approach for the formation of the double bond. Moreover, pentafluorophenyl diphenylphosphinate was found to be an efficient condensation reagent for the macrocyclization.

Métodos de preparação de lactonas de anel médio Methods for the preparation of medium ring lactones

Directory of Open Access Journals (Sweden)

Luiz S. Longo Junior

2007-04-01

Full Text Available There are several natural products bearing medium ring lactone moieties, which are those containing a ring size in the range of 8 to 11 members. This review intends to cover the last 10 years (1996-2005 of the literature concerning the synthesis of medium ring lactones.

Synthesis of several tetraaza macrocyclic amine ligands and the biodistribution of their Tc-complexes

International Nuclear Information System (INIS)

Ketring, A.R.

1982-01-01

Several macrocyclic tetraaza ligands were synthesized and their /sup 99m/Tc-complexes prepared. The biological distribution of these complexes was examined to determine their possible utility as radiodiagnostic agents. The simplest of the macrocyclic tetraaza ligands studied, cyclam, forms a very stable cationic complex with Tc when pertechnetate is reduced with stannous ion in an aqueous solution of the ligand. When injected intravenously into mice Tc-cyclam was excreted predominantly by the urinary system. Derivatives of cyclam which were synthesized contained aromatic or aliphatic substituents and formed more lipophilic complexes with Tc. The complexes were formed in high yield as determined by paper chromatography, thin layer chromatography, electrophoresis and/or high performance liquid chromatography. Relative lipophilicities were determined for the complexes by octanol-to-water extractions. Animal studies using mice indicated there was an inverse relationship between the octanol-to-water extraction ratio and urinary excretion. Two of the complexes having relatively high octanol-to-water extraction ratios were significantly excreted by the hepatobiliary system with localization in the gall bladder. The complex having the highest octanol-to-water ratio was not excreted significantly by the hepatobiliary system, but cleared very slowly from the blood and localized in the liver, lungs, spleen and to some extent the heart. Derivatization of cyclam can be performed without greatly reducing its ability to complex Tc but greatly influencing the biological distribution of its Tc complex. This indicates that there is a potential for preparing radiodiagnostic agents using macrocyclic tetraaza ligands

Metacridamides A and B, bioactive macrocycles from conidia of the entomopathogenic fungus Metarhizium acridum

Science.gov (United States)

Metarhizium acridum, an entomopathogenic fungus, has been commercialized and used successfully for biocontrol of grasshopper pests in Africa and Australia. Its conidia produce two novel 17-membered macrocycles, metacridamides A (1) and B (2), which consist of a Phe unit condensed with a nonaketide....

On solvent extraction of metals by macrocyclic polyethers

International Nuclear Information System (INIS)

Ionov, V.P.

1984-01-01

The Ksub(γ) parameter characterizing effective ion charges in ionic associates of metal salts is suggested; these charges parallel with other factors determine the metals extraction by macrocyclic polyethers (crown-ethers). The dependence of metal extraction constant on the Ksub(γ) parameter is discussed. It is shown that the less effective cation charge of alkali metal ionic associates, the more probable its entering the crown-ether cavity. The synergetic crown-ethers extraction is bound as well with Ksub(γ) of metal salts. The differences in the cation extraction constants having the same ionic radius are explained with account of different values of Ksub(γ) parameters of these salts

Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions.

Science.gov (United States)

Park, Yongho; Harper, Kaid C; Kuhl, Nadine; Kwan, Eugene E; Liu, Richard Y; Jacobsen, Eric N

2017-01-13

Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction. Copyright © 2017, American Association for the Advancement of Science.

ROLE OF MEMBRANE LIPID-COMPOSITION IN THE CYTOTOXICITY OF THE SESQUITERPENE LACTONE EUPATORIOPICRIN

NARCIS (Netherlands)

VANDERLINDE, JCC; WOERDENBAG, HJ; MALINGRE, TM; KAMPINGA, HH; KONINGS, AWT

1993-01-01

The aim of the present study was to investigate a possible role of lipid peroxidation in the cytotoxicity of eupatoriopicrin, the principal sesquiterpene lactone from Eupatorum cannabinum L. Incorporation of arachidonic acid acyl chains in the phospholipids of cellular membranes of mouse fibroblast

Cytotoxic and antibacterial activities of sesquiterpene lactones isolated from Tanacetum praeteritum subsp praeteritum

NARCIS (Netherlands)

Goren, N; Woerdenbag, HJ; BozokJohansson, C

1996-01-01

Ten sesquiterpene lactones and one sesquiterpene isolated from Tanacetum praeteritum subsp. praeteritum: 1 alpha,6 alpha-dihydroxyisocostic acid methyl ester (2), 1 alpha-hydroxy-1-deoxoarglanine (3), douglanin (5), santamarin (6), reynosin (7), 1-epi-tatridin B (8), ludovicin A (10), armexin (12),

Rhamnolipids and lactonic sophorolipids: natural antimicrobial surfactants for oral hygiene.

Science.gov (United States)

Elshikh, M; Moya-Ramírez, I; Moens, H; Roelants, S; Soetaert, W; Marchant, R; Banat, I M

2017-11-01

To assess the efficacy of rhamnolipid (mixture of monorhamnolipid and dirhamnolipid congeners), purified monorhamnolipid, dirhamnolipid and lactonic sophorolipid biosurfactants against pathogens important for oral hygiene. Acquired and produced biosurfactants were fully characterized to allow the antimicrobial activity to be assigned to the biosurfactant congeners. Antimicrobial activity was assessed using the resazurin-aided microdilution method. Mixed rhamnolipid JBR425 (MR) and lactonic sophorolipids (LSLs) demonstrated the lowest minimum inhibitory concentration (MIC) which ranged between 100 and 400 μg ml -1 against Streptococcus mutans, Streptococcus oralis, Actinomyces naeslundii, Neisseria mucosa and Streptococcus sanguinis. Combining these biosurfactants with standard antimicrobial agents namely chlorhexidine, sodium lauryl sulphate, tetracycline HCl and ciprofloxacin showed a dramatic drop in the MIC values. In addition, in vitro studies demonstrated the biosurfactants' ability to prevent and disrupt oral pathogens biofilms. The increased permeability of microorganisms treated with biosurfactant, as shown using bisbenzimide dye, in part explains the inhibition effect. The results demonstrate that rhamnolipids and LSLs have the ability to inhibit oral pathogens both in planktonic and oral biofilm states. The findings indicate the potential value of biosurfactants for both oral hygiene and the pharmaceutical industries since there is a serious need to reduce the reliance on synthetic antimicrobials and antibiotics. © 2017 The Society for Applied Microbiology.

Synthesis and characterization of Ni(II, Cu(II and Co(III complexes with polyamine-containing macrocycles bearing an aminoethyl pendant arm

Directory of Open Access Journals (Sweden)

K. S. SIDDIQI

2004-09-01

Full Text Available Reaction of [M(ppn2]X2 (where M = Cu(II, Ni(II, Co(II and ppn = 1,3-diaminopropane with formaldehyde and ethylenediamine in methanol results in the ready formation of a 16-membered macrocyclic complex. The complexes were characterized by elemental anlysis, IR, EPR, electronic spectral data, magnetic moments and conductance measurements. The Cu(II, Ni(II and Co(III complexes are coordinated axially with both pendant groups of the hexadentate macrocycle. These pendant donors are attached to the macrocycle by a carbon chain. The electrical conductivities of the Cu(II and Ni(II chelates indicated them to be 1:2 electrolytes whilst those of Co(III is a 1:3 electrolyte in DMSO. The EPR spectrum of the copper complex exhibited G at 3.66, which indicates a considerable exchange interaction in the complex. Spectroscopic evidence suggests that in all of the complexes the metal ion is in an octahedral environment.

N-acyl-L-homoserine lactone-mediated regulation of the Lip secretion system in Serratia liquefaciens MG1

DEFF Research Database (Denmark)

Riedel, K.; Ohnesorg, T.; Krogfelt, K.A.

2001-01-01

The analysis of Serratia liquefaciens MG1 'luxAB insertion mutants that are responsive to N-butanoyl-L-homoserine lactone revealed that expression of lipB is controlled by the swr quorum-sensing system. LipB is part of the Lip exporter, a type I secretion system, which is responsible for the secr......The analysis of Serratia liquefaciens MG1 'luxAB insertion mutants that are responsive to N-butanoyl-L-homoserine lactone revealed that expression of lipB is controlled by the swr quorum-sensing system. LipB is part of the Lip exporter, a type I secretion system, which is responsible...

Evaluation of the efficacy of ProHeart® 6 (moxidectin) against a resistant isolate of Dirofilaria immitis (JYD-34) in dogs.

Science.gov (United States)

Bowman, Dwight D; McTier, Tom L; Adams, Eric L; Mahabir, Sean P; Login, Joyce A; Bidgood, Tara; Woods, Debra J

2017-11-09

In a previous study, it was demonstrated that ProHeart ® 6 (PH6) (moxidectin, Zoetis) provided only about 20% efficacy in a small six-dog study against a macrocyclic lactone -resistant Dirofilaria immitis isolate (Jd2009-2) when dogs were inoculated with infective third-stage larvae (L3) at the end of the dosing period (ie, 180 days post treatment). The objective of the current study was to determine the prophylactic efficacy of a moxidectin sustained-release formulation (PH6) against a confirmed macrocyclic lactone-resistant isolate of D. immitis (JYD-34) in dogs when administered by subcutaneous injection at the labeled dose of 0.17 mg/kg 2 days before L3 inoculation. This was intended to model the scenario where dogs become infected with resistant heartworms at the end of the PH6 treatment period (ie, 6 months post treatment) when dogs would routinely be given another injection under normal field use. Twelve purpose-bred Beagle dogs (six males and six females) were selected and randomly allocated to two groups, untreated controls and PH6-treated dogs in groups of six each. The dogs were ≥8 months old at the start of the study, and using blood samples collected on Day -7 were shown to be negative for adult heartworm antigen and microfilariae. On Day 0, the dogs in the untreated control group were administered saline subcutaneously by injection, and the dogs in the treated group were administered PH6 according to label instructions. On Day 2, each dog was inoculated in the inguinal area with 50 L3 of D. immitis. The dogs were necropsied on Day 150 (148 days post infection), and the worms were collected and counted. All of the six control dogs were infected and harbored a range of 21 to 37 worms (geometric mean, 25.4; 10.9 males and 13.9 females). Only one of the six PH6 dogs was found to be infected, harboring a single male worm. Efficacy was 99.5% (geometric mean). ProHeart ® 6 was highly effective in preventing the development of heartworms in dogs

Organic carbonates as solvents in macrocyclic Mn(III) salen catalyzed asymmetric epoxidation of non-functionalized olefins

Czech Academy of Sciences Publication Activity Database

Maity, N. Ch.; Rao, G. V. S.; Prathap, Kaniraj Jeya; Abdi, S. H. R.; Kureshy, R. I.; Khan, N. H.; Bajaj, H. C.

2013-01-01

Roč. 366, January (2013), s. 380-389 ISSN 1381-1169 Institutional support: RVO:61388963 Keywords : asymmetric epoxidation * organic carbonate * macrocyclic Mn(III) salen complex Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.679, year: 2013

Antiplasmodial activities and cytotoxic effects of aqueous extracts and sesquiterpene lactones from Neurolaena lobata

NARCIS (Netherlands)

Francois, G; Passreiter, CM; Woerdenbag, HJ; VanLooveren, M

Aqueous and lipophilic extracts of Neurolaena lobata (Asteraceae), obtained from Guatemala, were tested against Plasmodium falciparum in vitro. Moreover, sesquiterpene lactones, of the germacranolide and furanoheliangolide type, isolated from N. lobata, were shown to be active against P. falciparum

Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.

Science.gov (United States)

Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

2010-06-01

The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

Carboxymethyl glycoside lactone(CMGL) synthons:Scope of the method and preliminary results on step growth polymerization of α-azide-ω-alkyne glycomonomers

Institute of Scientific and Technical Information of China (English)

CHAMBERT; Stéphane; BERNARD; Julien; FLEURY; Etienne; QUENEAU; Yves

2010-01-01

Carboxymethyl glycoside lactones(CMGLs) are bicyclic synthons which open readily for accessing new types of pseudo-glycoconjugates,such as sugar-amino acid hybrids,neoglycolipids,pseudodisaccharides,and membrane imaging systems.After lactone opening,free OH-2 is available for further functionalization,leading to 1,2-bisfunctionalized derivatives.This strategy is illustrated herein with new polymerizable systems of the AB type bearing both azide and alkyne functions prepared from α or β gluco-CMGL synthons.After the reaction of lactones with propargylamine,an azido group was introduced by two different sequences leading to either the 2-manno-azido or the 6-gluco-azido products.The capability of these AB monomers to undergo step growth polymerization through copper(I) catalyzed alkyne-azide cycloaddition(CuAAC) and generate glycopolytriazoles was evidenced.

Immunobiological properties of sesquiterpene lactones obtained by chemically transformed structural modifications of trilobolide

Czech Academy of Sciences Publication Activity Database

Harmatha, Juraj; Vokáč, Karel; Buděšínský, Miloš; Zídek, Zdeněk; Kmoníčková, Eva

2015-01-01

Roč. 107, Dec (2015), s. 90-99 ISSN 0367-326X R&D Projects: GA ČR GA305/07/0061 Institutional support: RVO:61388963 ; RVO:68378041 Keywords : sesquiterpene lactones * guaianolides * trilobolide derivatives * nitric oxide * cytokines * immunoactivity Subject RIV: CC - Organic Chemistry Impact factor: 2.408, year: 2015

A method for the preparation of lipophilic macrocyclic technetium-99m complexes

International Nuclear Information System (INIS)

Troutner, D.E.; Volkert, W.A.

1991-01-01

A procedure for the preparation of technetium complexes applicable as diagnostic radiopharmaceuticals is suggested and documented with 27 examples. Technetium-99m is reacted with a suitable complexant selected from the class of alkylenamine oximes containing 2 or 3 carbon atoms in the alkylene group. The lipophilic macrocyclic complexes possess an amine, amide, carboxy, carboxy ester, hydroxy or alkoxy group or a suitable electron acceptor group. (M.D.). 7 tabs

Stability and kinetics of uranyl ion complexation by macrocycles in propylene carbonate

International Nuclear Information System (INIS)

Fux, P.

1984-06-01

A thermodynamic study of uranyl ion complexes formation with different macrocyclic ligands was realized in propylene carbonate as solvent using spectrophotometric and potentiometric techniques. Formation kinetics of two UO 2 complexes: a crown ether (18C6) and a coronand (22) was studied by spectrophotometry in propylene carbonate with addition of tetraethylammonium chlorate 0.1M at 25 0 C. Possible structures of complexes in solution are discussed [fr

Total synthesis of haterumalides NA and NC via a chromium-mediated macrocyclization.

Science.gov (United States)

Schomaker, Jennifer M; Borhan, Babak

2008-09-17

The syntheses of haterumalides NA and NC were accomplished via the macrocyclization of a chlorovinylidene chromium carbenoid onto a pendant aldehyde to generate the C8-C9 bond with the desired stereoisomer as the major product. Utilizing the latter chemistry enables access to both C9 hydroxylated (haterumalides NC and ND) and C9 deoxygenated forms (haterumalides NA, NB, and NE; via deoxygenation of the C9-hydroxyl).

Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S-3-(Oxiran-2-ylpropanoates from Renewable Levoglucosenone: An Access to Enantiopure (S-Dairy Lactone

Directory of Open Access Journals (Sweden)

Aurélien A. M. Peru

2016-07-01

Full Text Available Chiral epoxides—such as ethyl and methyl (S-3-(oxiran-2-ylpropanoates ((S-1a/1b—are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation in low to moderate overall yield (20%–50%. Moreover, this procedure requires some harmful reagents such as sodium nitrite ((ecotoxic and borane (carcinogen. Herein, starting from levoglucosenone (LGO, a biobased chiral compound obtained through the flash pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo-enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation, palladium-catalyzed hydrogenation, tosylation and treatment with sodium ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S-3-(oxiran-2-ylpropanoates in 57% overall yield, respectively. To demonstrate the potentiality of this new synthetic pathway from LGO, the synthesis of high value-added (S-dairy lactone was undertaken from these epoxides and provided the target in 37% overall yield from LGO.

Development of pyridine-containing macrocyclic copper(II) complexes: potential role in the redox modulation of oxaliplatin toxicity in human breast cells.

Science.gov (United States)

Fernandes, Ana S; Costa, Judite; Gaspar, Jorge; Rueff, José; Cabral, M Fátima; Cipriano, Madalena; Castro, Matilde; Oliveira, Nuno G

2012-09-01

The unique redox and catalytic chemistry of Cu has justified the development of novel Cu complexes for different therapeutic uses including cancer therapy. In this work, four pyridine-containing aza-macrocyclic copper(II) complexes were prepared (CuL1-CuL4) varying in ring size and/or substituents and their superoxide scavenging activity evaluated. CuL3, the most active superoxide scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells. CuL3 is thus a promising complex to be further studied and to be used as a lead compound for the optimization of novel chemotherapy sensitizers.

Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Wu, H; Song, Z; Hentzer, Morten

2000-01-01

The pathogenesis of Pseudomonas aeruginosa is associated with expression of virulence factors, many of which are controlled by two N:-acylhomoserine lactone (AHL)-based quorum-sensing systems. Escherichia coli strains equipped with a luxR-based monitor system expressing green fluorescent protein ...

N-acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms

DEFF Research Database (Denmark)

Riedel, K.; Hentzer, Morten; Geisenberger, O.

2001-01-01

Pseudomonas aeruginosa and Burkholderia cepacia are capable of forming mixed biofilms in the lungs of cystic fibrosis patients. Both bacteria employ quorum-sensing systems, which rely on N-acylhomoserine lactone (AHL) signal molecules, to co- ordinate expression of virulence factors with the form...

Binding of carbon dioxide to metal macrocycles: Toward a mechanistic understanding of electrochemical and photochemical carbon dioxide reduction

Energy Technology Data Exchange (ETDEWEB)

Fujita, E.

1993-01-01

Efforts were made to find effective catalysts for photochemical and electrochemical reduction of CO[sub 2]. We are studying the factors controlling excited-state lifetimes, electron-transfer rates to mediators/catalysts, properties of reduced mediators, binding of small molecules to reduced mediators, and reactivity of the mediators to yield the desired products. This document describes some of the results of binding on CO[sub 2] to metal macrocycles. The electrocatalytic activity of cobalt macrocycle complexes in reduction of CO[sub 2] in CO[sub 2]-saturated water at the Hg electrode is being studied. We are ready to study the mechanism and kinetics of the photochemical CO[sub 2] reduction in order to design more efficient photo-energy conversion systems. 19 refs.

Binding of carbon dioxide to metal macrocycles: Toward a mechanistic understanding of electrochemical and photochemical carbon dioxide reduction

Energy Technology Data Exchange (ETDEWEB)

Fujita, E.

1993-07-01

Efforts were made to find effective catalysts for photochemical and electrochemical reduction of CO{sub 2}. We are studying the factors controlling excited-state lifetimes, electron-transfer rates to mediators/catalysts, properties of reduced mediators, binding of small molecules to reduced mediators, and reactivity of the mediators to yield the desired products. This document describes some of the results of binding on CO{sub 2} to metal macrocycles. The electrocatalytic activity of cobalt macrocycle complexes in reduction of CO{sub 2} in CO{sub 2}-saturated water at the Hg electrode is being studied. We are ready to study the mechanism and kinetics of the photochemical CO{sub 2} reduction in order to design more efficient photo-energy conversion systems. 19 refs.

A critical review of producers of small lactone mycotoxins: patulin, penicillic acid and moniliformin

DEFF Research Database (Denmark)

Frisvad, J.C.

2018-01-01

A very large number of filamentous fungi has been reported to produce the small lactone mycotoxins patulin, penicillic acid and moniliformin. Among the 167 reported fungal producers of patulin, only production by 29 species could be confirmed. Patulin is produced by 3 Aspergillus species, 3...

Quantum chemical DFT study of the interaction between molecular oxygen and FeN₄ complexes, and effect of the macrocyclic ligand.

Science.gov (United States)

Silva, Adilson Luís Pereira; de Almeida, Luciano Farias; Marques, Aldaléa Lopes Brandes; Costa, Hawbertt Rocha; Tanaka, Auro Atsushi; da Silva, Albérico Borges Ferreira; de Jesus Gomes Varela, Jaldyr

2014-03-01

Density functional theory (DFT) was used to examine the interaction between molecular oxygen (O₂) and macrocyclic iron complexes of the type FeN₄ during the formation of FeN₄--O₂ adducts. In order to understand how this interaction is affected by different macrocyclic ligands, O₂ was bonded to iron-tetraaza[14]annulene (FeTAA), iron-tetramethyl-tetraaza[14]annulene (FeTMTAA), iron-hexamethyl-tetraaza[14]annulene (FeHMTAA), iron dibenzotetraaza[14]annulene (FeDBTAA), and two iron-tetramethyl-dibenzotetraaza[14]annulene complexes (FeTMDBTAA1, FeTMDBTAA2). The ground state for FeN₄-O₂ adducts was the open-shell singlet. Analysis of the factors influencing the O₂ bonding process showed that different macrocyclic ligands yielded adducts with differences in O--O and Fe--O₂ bond lengths, total charge over the O₂ fragment, O--O vibrational frequency, and spin density in the O₂ fragment. A smaller energy gap between the α-HOMO of the FeN₄ complexes and the β-LUMO of O₂ increased the interaction between the complex and the O₂ molecule. The order of activity was FeDBTAA < FeTMDBTAA2 < FeTMDBTAA1 < FeTAA < FeTMTAA < FeHMTAA.

Detekce polymorfismu v genu MDR1 u ovčáckých a honáckých psů

OpenAIRE

Staroveská, Marieta

2016-01-01

This thesis is focused on polymorphism of MDR1 gene and related drug resistance. Resistance is caused by deletion of four nucleotids, that resulting in a frame shift and synthesis of nonfunctional transport of P-glycoprotein. The text describes a polymorphism of MDR1 (ABCB1) gene, which results in reduced resistance to drugs belonging to the group of macrocyclic lactones. It also describes inheritance of this phenomenon and it deals with the detection of mutation using PCR (polymerase chain r...

Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.

Science.gov (United States)

Giroud, Maude; Dietzel, Uwe; Anselm, Lilli; Banner, David; Kuglstatter, Andreas; Benz, Jörg; Blanc, Jean-Baptiste; Gaufreteau, Delphine; Liu, Haixia; Lin, Xianfeng; Stich, August; Kuhn, Bernd; Schuler, Franz; Kaiser, Marcel; Brun, Reto; Schirmeister, Tanja; Kisker, Caroline; Diederich, François; Haap, Wolfgang

2018-04-26

Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei ( T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors ( K i < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC 50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined. When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for untreated controls) mean days of survival.

The Pseudomonas aeruginosa autoinducer dodecanoyl-homoserine lactone inhibits the putrescine synthesis in human cells

DEFF Research Database (Denmark)

Kristiansen, S.; Bjarnsholt, Thomas; Adeltoft, D.

2008-01-01

Pseudomonas aeruginosa uses acyl-homoserine lactones to coordinate gene transcription in a process called quorum sensing (QS). The QS molecules C-4-HSL and C-12-oxo-HSL are synthesized from the universal precursor S-adenosyl methionine, which is also a precursor of polyamines in human cells...

Transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in Yersinia pestis [corrected].

Directory of Open Access Journals (Sweden)

Christopher N LaRock

Full Text Available The etiologic agent of bubonic plague, Yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. Though the closely related enteric pathogen Y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in Y. pestis has been unclear. In this study we performed transcriptional profiling experiments to identify Y. pestis quorum sensing regulated functions. Our analysis revealed that acyl-homoserine lactone-based quorum sensing controls the expression of several metabolic functions. Maltose fermentation and the glyoxylate bypass are induced by acyl-homoserine lactone signaling. This effect was observed at 30°C, indicating a potential role for quorum sensing regulation of metabolism at temperatures below the normal mammalian temperature. It is proposed that utilization of alternative carbon sources may enhance growth and/or survival during prolonged periods in natural habitats with limited nutrient sources, contributing to maintenance of plague in nature.

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

OpenAIRE

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.; Kingston, David G. I.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 an...

Identification of New Lactone Derivatives Isolated from Trichoderma sp., An Endophytic Fungus of Brotowali (Tinaspora crispa

Directory of Open Access Journals (Sweden)

ELFITA

2014-03-01

Full Text Available Endophytic fungi is a rich source of novel organic compounds with interesting biological activities and a high level of structural diversity. As a part of our systematic search for new bioactive lead structures and specific profiles from endophytic fungi, an endophytic fungus was isolated from roots of brotowali (Tinaspora crispa, an important medicinal plant. Colonial morphological trait and microscopic observation revealed that the endophytic fungus was Trichoderma sp. The pure fungal strain was cultivated on 7 L Potatos Dextose Broth (PDB medium under room temperature (no shaking for 8 weeks. The ethyl acetate were added to cultur medium and left overnight to stop cell growth. The culture filtrates were collected and extracted with EtOAc and then taken to evaporation. Two new lactone derivatives, 5-hydroxy-4-hydroxymethyl-2H-pyran-2-one (1 and (5-hydroxy-2-oxo-2H pyran-4-yl methyl acetate (2 were obtained from the EtOAc extracts of Trichoderma sp. Their structures were determined on the basic of spectroscopic methods including UV, IR, 1H-NMR, 13C-NMR, HMQC, and HMBC.

Recognition of thymine in DNA bulges by a Zn(II) macrocyclic complex.

Science.gov (United States)

del Mundo, Imee Marie A; Fountain, Matthew A; Morrow, Janet R

2011-08-14

A Zn(II) macrocyclic complex with appended quinoline is a bifunctional recognition agent that uses both the Zn(II) center and the pendent aromatic group to bind to thymine in bulges with good selectivity over DNA containing G, C or A bulges. Spectroscopic studies show that the stem containing the bulge stays largely intact in a DNA hairpin with the Zn(II) complex bound to the thymine bulge. This journal is © The Royal Society of Chemistry 2011

Quartz Microbalance Sensor for the Detection of Acrylamide

Directory of Open Access Journals (Sweden)

Christoph A. Schalley

2004-10-01

Full Text Available Abstract: Several macrocycles of the Hunter-Vögtle type have been identified as superior host compounds for the detection of small amounts of acrylamide. When coated onto the surface of a quartz microbalance, these compounds serve as highly sensitive and selective sensor-active layers for their use in electronic noses. In this study, differently substituted macrocycles were investigated including an open-chain analogue and a catenane. Their structure and functional groups are correlated with their observed affinities to acrylamide and related acids and amides. The much smaller response of the open-chain compound and the almost absent sensor response of the catenane suggest that binding occurs within the cavity of the macrocycle. Theoretical calculations agree well with the experimental data even though they do not yet take into account the arrangement of the macrocycles in the sensor-active layer. The lower detection limit of acrylamide is 10 parts per billion (ppb, which is impressively low for this type of sensor. Other related compounds such as acrylic acid, propionamide, or propionic acid show no or significantly lower affinities to the macrocycles in these concentration ranges.

Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1

NARCIS (Netherlands)

Sio, CF; Otten, LG; Cool, RH; Diggle, SP; Braun, PG; Daykin, M; Camara, M; Williams, P; Quax, WJ; Bos, R

The virulence of the opportunistic human pathogen Pseudomonas aeruginosa PAO1 is controlled by an N-acyl-homoserine lactone (AHL)-dependent quorum-sensing system. During functional analysis of putative acylase genes in the P. aeruginosa PAO1 genome, the PA2385 gene was found to encode an acylase

Synergistic extraction of some divalent metal cations into nitrobenzene by using strontium dicarbollylcobaltate and electroneutral macrocyclic lactam receptor

Czech Academy of Sciences Publication Activity Database

Makrlík, E.; Sedláková, Zdeňka; Vaňura, P.; Selucký, P.

2013-01-01

Roč. 295, č. 3 (2013), s. 2263-2266 ISSN 0236-5731 Institutional support: RVO:61389013 Keywords : divalent metal cations * macrocyclic lactam receptor * complexation Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.415, year: 2013

Synthesis and anion binding properties of porphyrins and related compounds

KAUST Repository

Figueira, Flávio

2016-12-02

Over the last two decades the preparation of pyrrole-based receptors for anion recognition has attracted considerable attention. In this regard porphyrins, phthalocyanines and expanded porphyrins have been used as strong and selective receptors while the combination of those with different techniques and materials can boost their applicability in different applications as chemosensors and extracting systems. Improvements in the field, including the synthesis of this kind of compounds, can contribute to the development of efficient, cheap, and easy-to-prepare anion receptors. Extensive efforts have been made to improve the affinity and selectivity of these compounds and the continuous expansion of related research makes this chemistry even more promising. In this review, we summarize the most recent developments in anion binding studies while outlining the strategies that may be used to synthesize and functionalize these type of macrocycles. © 2016 World Scientific Publishing Company.

Kinetic Analysis for Macrocyclizations Involving Anionic Template at the Transition State

Directory of Open Access Journals (Sweden)

Vicente Martí-Centelles

2012-01-01

competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes.

Hydrolysis of Letrozole catalyzed by macrocyclic Rhodium (I) Schiff-base complexes.

Science.gov (United States)

Reddy, P Muralidhar; Shanker, K; Srinivas, V; Krishna, E Ravi; Rohini, R; Srikanth, G; Hu, Anren; Ravinder, V

2015-03-15

Ten mononuclear Rhodium (I) complexes were synthesized by macrocyclic ligands having N4 and N2O2 donor sites. Square planar geometry is assigned based on the analytical and spectral properties for all complexes. Rh(I) complexes were investigated as catalysts in hydrolysis of Nitrile group containing pharmaceutical drug Letrozole. A comparative study showed that all the complexes are efficient in the catalysis. The percent yields of all the catalytic reaction products viz. drug impurities were determined by spectrophotometric procedures and characterized by spectral studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Routine patch testing with the sesquiterpene lactone mix in Europe: a 2-year experience

DEFF Research Database (Denmark)

Paulsen, E; Andersen, Klaus Ejner; Brandão, F M

1999-01-01

To test the screening value of the sesquiterpene lactone (SL) mix in Europe today and describe epidemiological and clinical features of Compositae-sensitive patients, the SL mix 0.1% pet. was included in the standard patch test series in 11 European clinics. 10,695 patients were tested, and 106 (1...

Copper(i)-induced amplification of a [2]catenane in a virtual dynamic library of macrocyclic alkenes

NARCIS (Netherlands)

Berrocal, J.A.; Nieuwenhuizen, M.M.L.; Mandolini, L.; Meijer, E.W.; Di Stefano, S.

2014-01-01

Olefin cross-metathesis of diluted dichloromethane solutions (=0.15 M) of the 28-membered macrocyclic alkene C1, featuring a 1,10-phenanthroline moiety in the backbone, as well as of catenand 1, composed of two identical interlocked C1 units, generates families of noninterlocked oligomers Ci. The

Templated synthesis of cyclic [4]rotaxanes consisting of two stiff rods threaded through two bis-macrocycles with a large and rigid central plate as spacer.

Science.gov (United States)

Collin, Jean-Paul; Durola, Fabien; Frey, Julien; Heitz, Valérie; Reviriego, Felipe; Sauvage, Jean-Pierre; Trolez, Yann; Rissanen, Kari

2010-05-19

Two related cyclic [4]rotaxanes consisting of double macrocycles and rigid rods incorporating two bidentate chelates have each been prepared in high yield. The first step is a multigathering and threading reaction driven by coordination of two different bidentate chelates (part of either the rings or the rods) to each copper(I) center so as to afford the desired precursor. In both cases, the assembly step is done under very mild conditions, and it is quantitative. The second key reaction is the stopper-attaching reaction, based on click chemistry. Even if the quadruple stoppering reaction is not quantitative, it is relatively high-yielding (60% and 95%), and the copper-driven assembly process is carried out at room temperature without any aggressive reagent. The final copper-complexed [4]rotaxanes obtained contain two aromatic plates roughly parallel to one another located at the center of each bis-macrocycle. In the most promising case in terms of host-guest properties, the plates are zinc(II) porphyrins of the tetra-aryl series. The compounds have been fully characterized by various spectroscopic techniques ((1)H NMR, mass spectrometry, and electronic absorption spectroscopy). Unexpectedly, the copper-complexed porphyrinic [4]rotaxane could be crystallized as its 4PF(6)(-) salt to afford X-ray quality crystals. The structure obtained is in perfect agreement with the postulated chemical structure of the compound. It is particularly attractive in terms of symmetry and molecular aesthetics. The distance between the zinc atoms of the two porphyrins is 8.673 A, which is sufficient to allow insertion between the two porphyrinic plates of small ditopic basic substrates able to interact with the central porphyrinic Zn atoms. This prediction has been confirmed by absorption spectroscopy measurements in the presence of various organic substrates. However, large substrates cannot be introduced in the corresponding recognition site and are thus complexed mostly in an exo

Corrosion mitigation of J55 steel in 3.5% NaCl solution by a macrocyclic inhibitor

Energy Technology Data Exchange (ETDEWEB)

Singh, Ambrish [State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation (Southwest Petroleum University), Chengdu, Sichuan 610500 (China); Department of Chemistry, LFTS, Lovely Professional University, Phagwara, Punjab 144402 (India); Lin, Yuanhua, E-mail: yhlin28@163.com [State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation (Southwest Petroleum University), Chengdu, Sichuan 610500 (China); Obot, I.B. [Centre of Research Excellence in Corrosion, Research Institute, King Fahd University of Petroleum and Minerals, Dhahran 31261 (Saudi Arabia); Ebenso, Eno E. [Department of Chemistry, School of Mathematical & Physical Sciences, North-West University (Mafikeng Campus), Private Bag X2046, Mmabatho 2735 (South Africa); Material Science Innovation & Modelling (MaSIM) Focus Area, Faculty of Agriculture, Science and Technology, North-West University (Mafikeng Campus), Private Bag X2046, Mmabatho 2735 (South Africa); Ansari, K.R.; Quraishi, M.A. [Department of Applied Chemistry, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, Uttar Pradesh (India)

2015-11-30

Graphical abstract: SECM studies revealed decrease of steady current in the presence of inhibitor while it increased for 3.5% NaCl solution that acted as the conductor. - Highlights: • J55 steel protection in 3.5% NaCl solution saturated with CO{sub 2} by HPT. • Potentiodynamic polarization curves reveal that the actions of HPT are mixed type. • The adsorption of HPT obeys the Langmuir adsorption isotherm. • Scanning electrochemical microscopy is used to discuss the insulated and conductive surface. - Abstract: 1,2,4,7,9,10-Hexaazacyclo-pentadeca-10,15-dien-3,5,6,8-tetraone (HPT) a macrocyclic compound has been studied using electrochemical methods and scanning electrochemical microscopy (SECM) techniques. The R{sub ct} values increased and C{sub dl} values decreased with the increase in concentration of the inhibitor. The corrosion inhibition of J55 steel in 3.5 wt.% NaCl solution saturated with CO{sub 2} by polarization studies revealed that HPT acted as a mixed type inhibitor. The adsorption of HPT on the J55 steel surface obeyed the Langmuir adsorption isotherm. The thermodynamic parameters (K{sub ads}, ΔG°{sub ads}) were also computed and discussed.

Corrosion mitigation of J55 steel in 3.5% NaCl solution by a macrocyclic inhibitor

International Nuclear Information System (INIS)

Singh, Ambrish; Lin, Yuanhua; Obot, I.B.; Ebenso, Eno E.; Ansari, K.R.; Quraishi, M.A.

2015-01-01

Graphical abstract: SECM studies revealed decrease of steady current in the presence of inhibitor while it increased for 3.5% NaCl solution that acted as the conductor. - Highlights: • J55 steel protection in 3.5% NaCl solution saturated with CO 2 by HPT. • Potentiodynamic polarization curves reveal that the actions of HPT are mixed type. • The adsorption of HPT obeys the Langmuir adsorption isotherm. • Scanning electrochemical microscopy is used to discuss the insulated and conductive surface. - Abstract: 1,2,4,7,9,10-Hexaazacyclo-pentadeca-10,15-dien-3,5,6,8-tetraone (HPT) a macrocyclic compound has been studied using electrochemical methods and scanning electrochemical microscopy (SECM) techniques. The R ct values increased and C dl values decreased with the increase in concentration of the inhibitor. The corrosion inhibition of J55 steel in 3.5 wt.% NaCl solution saturated with CO 2 by polarization studies revealed that HPT acted as a mixed type inhibitor. The adsorption of HPT on the J55 steel surface obeyed the Langmuir adsorption isotherm. The thermodynamic parameters (K ads , ΔG° ads ) were also computed and discussed.

Enantioseparation and chiral recognition mechanism of new chiral derivatives of xanthones on macrocyclic antibiotic stationary phases.

Science.gov (United States)

Fernandes, Carla; Tiritan, Maria Elizabeth; Cass, Quezia; Kairys, Visvaldas; Fernandes, Miguel Xavier; Pinto, Madalena

2012-06-08

A chiral HPLC method using four macrocyclic antibiotic chiral stationary phases (CSPs) has been investigated for determination of the enantiomeric purity of fourteen new chiral derivatives of xanthones (CDXs). The separations were performed with the CSPs Chirobiotic T, Chirobiotic TAG, Chirobiotic V and Chirobiotic R under multimodal elution conditions (normal-phase, reversed-phase and polar ionic mode). The analyses were performed at room temperature in isocratic mode and UV and CD detection at a wavelength of 254 nm. The best enantioselectivity and resolution were achieved on Chirobiotic R and Chirobiotic T CSPs, under normal elution conditions, with R(S) ranging from 1.25 to 2.50 and from 0.78 to 2.06, respectively. The optimized chromatographic conditions allowed the determination of the enantiomeric ratio of eight CDXs, always higher than 99%. In order to better understand the chromatographic behavior at a molecular level, and the structural features associated with the chiral recognition mechanism, computational studies by molecular docking were carried out using VDock. These studies shed light on the mechanisms involved in the enantioseparation for this important class of chiral compounds. Copyright © 2012 Elsevier B.V. All rights reserved.

Aroma compounds and characteristics of noble-rot wines of Chardonnay grapes artificially botrytized in the vineyard.

Science.gov (United States)

Wang, Xing-Jie; Tao, Yong-Sheng; Wu, Yun; An, Rong-Yan; Yue, Zhuo-Ya

2017-07-01

Aroma characteristics and their impact volatile components of noble-rot wines elaborated from artificial botrytized Chardonnay grapes, obtained by spraying Botrytis cinerea suspension in Yuquan vineyard, Ningxia, China, were explored in this work. Dry white wine made from normal-harvested grapes and sweet wine produced from delay-harvested grapes were compared. Wine aromas were analysed by trained sensory panelists, and aroma compounds were determined by SPME-GC-MS. Results indicated that esters, fatty acids, thiols, lactones, volatile phenols and 2-nonanone increased markedly in noble-rot wines. In addition to typical aromas of noble-rot wines, artificial noble-rot wines were found to contain significant cream and dry apricot attributes. Partial Least-Squares Regression models of aroma characteristics against aroma components revealed that non-fermentative odorants were the primary contributor to dry apricot attribute, especially, thiols, C13-norisoprenoids, lactones, terpenols and phenolic acid derivatives, while cream attribute was dependent on both fermentative and non-fermentative volatile components. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sesquiterpene lactone mix as a diagnostic tool for Asteraceae allergic contact dermatitis: chemical explanation for its poor performance and Sesquiterpene lactone mix II as a proposed improvement.

Science.gov (United States)

Jacob, Mathias; Brinkmann, Jürgen; Schmidt, Thomas J

2012-05-01

Two preparations are currently in use for the diagnosis of allergic contact dermatitis caused by Asteraceae: (i) Sesquiterpene lactone (SL) mix [three pure sesquiterpene lactones (STLs)], whose use has been questioned, owing to an insufficient rate of true-positive results; and (ii) Compositae mix, consisting of five Asteraceae extracts, which is problematic because of lack of standardization and questionable reproducibility. To analyse the reasons for the narrow sensitivity of SL mix from a chemoinformatic point of view, and to propose a solution by rational selection of alternative constituents for a new SL mix II covering a broader cohort of allergic patients. Structural and biological information on allergenic STLs was retrieved from databases and the literature, and molecular modelling and chemoinformatic computations were performed. An explanation for the insufficient hit rate of SL mix is that the three constituents possess extremely similar molecular structures/properties and do not represent well the structural diversity of allergenic STLs. STLs that are known as constituents of Compositae mix plants show much a wider diversity, which explains the higher positive rate. On the basis of their positions in chemical property space, a new collection of STLs that more evenly cover the overall structural diversity spectrum is proposed. SL mix II is likely to detect a larger number of patients sensitized to Asteraceae. © 2012 John Wiley & Sons A/S.

Synthesis and biological evaluation of triazole-containing N-acyl homoserine lactones as quorum sensing modulators

DEFF Research Database (Denmark)

Stacy, Danielle M.; Le Quement, Sebastian T.; Hansen, Casper L.

2013-01-01

triazole-containing analogs of natural N-acyl l-homoserine lactone (AHL) signals as non-native QS agonists and antagonists in Gram-negative bacteria. We synthesized 72 triazole derivatives of five broad structure types in high yields and purities using efficient Cu(i)-catalyzed azide–alkyne couplings...

l-Galactono-gamma-lactone dehydrogenase from Arabidopsis thaliana, a flavoprotein involved in vitamin C biosynthesis.

NARCIS (Netherlands)

Leferink, N.G.H.; Berg, van den W.A.M.; Berkel, van W.J.H.

2008-01-01

l-Galactono-1,4-lactone dehydrogenase (GALDH; ferricytochrome c oxidoreductase; EC 1.3.2.3) is a mitochondrial flavoenzyme that catalyzes the final step in the biosynthesis of vitamin C (l-ascorbic acid) in plants. In the present study, we report on the biochemical properties of recombinant

Exploring the Substrate Scope of Baeyer–Villiger Monooxygenases with Branched Lactones as Entry towards Polyesters

NARCIS (Netherlands)

Delgove, Marie; Fürst, Maximilian; Fraaije, Marco; Bernaerts, Katrien; de Wildeman, Stefaan

2018-01-01

Baeyer–Villiger monooxygenases (BVMOs) are biocatalysts that are able to convert cyclic ketones into lactones by the insertion of oxygen. The aim of this study was to explore the substrate scope of several BVMOs with (biobased) cyclic ketones as precursors for the synthesis of branched polyesters.

Exploring the substrate scope of Baeyer-Villiger monooxygenases with branched lactones as entry towards polyesters

NARCIS (Netherlands)

Delgove, Marie; Fürst, Maximilian; Fraaije, Marco; Bernaerts, Katrien; De Wildeman, Stefaan M A

2018-01-01

Baeyer-Villiger monooxygenases (BVMOs) are biocatalysts able to convert cyclic ketones to lactones by the insertion of oxygen. The aim of this study was to explore the substrate scope of several BVMOs with (biobased) cyclic ketones as precursors for the synthesis of branched polyesters.The product

BIOLOGICALLY ACTIVE COMPOUNDS OF ARTEMISIA ANNUA. ESSENTIAL OIL

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D. A. Konovalov

2016-01-01

Full Text Available Artemisia annua is a herblike annual plant which has been used in Chinese folk medicine for more than 2,000 years. In 1970-s sesquiterpenic lactone of artemisinin was isolated from the above-ground part of this plant. Today it is the most efficient known natural and synthetic compound for malaria treatment. The purpose of the study was to review the data from the open sources about a component composition of Artemisia annua essential oil in the spectrum of its pharmacological activity. Methods. The study was carried out using information and searching sources (PubMed, ScholarGoogle, library data bases (eLibrary, Cyberleninca, as well as the results of our studies. Results. We have established that aboveground part of Artemisia annua have a significant amount  of essential oil apart from the sesquiterpene lactones. Essential oil contains more than 120 components, which belong to different classes of natural compounds. The study for dynamics of the essential oil accumulation in the Artemisia annua herb showed that the amount of oil in the herb rises significantly during budding, reaching maximum value in blossom. Qualitative composition and quantitative content of certain components varies depending on ecological and  geographical factors,  plant growing phase, cultivation technology, drying methods etc. Well-known pharmacological studies of essential oil of the Artemisia annua characterize it as a prospective source for the development of new antimicrobial medicinal drugs. Besides, as the studies shown, it can be related to the 6 class according to K. Sidorov’s classification – “relatively non-hazardous substances”. Conclusion. The analysis of the open sources on the study of essential oil of Artemisia annua made by us, as well as the results of our own studies, including phytochemical studies allow characterizing the essential oil of Artemisia annua as a prospective source for the working out of new antimicrobial drugs.

Characteristics of N-Acylhomoserine Lactones Produced by Hafnia alvei H4 Isolated from Spoiled Instant Sea Cucumber

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Hong-Man Hou

2017-04-01

Full Text Available This study aimed to identify N-acylhomoserine lactone (AHL produced by Hafnia alvei H4, which was isolated from spoiled instant sea cucumber, and to investigate the effect of AHLs on biofilm formation. Two biosensor strains, Chromobacterium violaceum CV026 and Agrobacterium tumefaciens KYC55, were used to detect the quorum sensing (QS activity of H. alvei H4 and to confirm the existence of AHL-mediated QS system. Thin layer chromatography (TLC and high resolution triple quadrupole liquid chromatography/mass spectrometry (LC/MS analysis of the AHLs extracted from the culture supernatant of H. alvei H4 revealed the existence of at least three AHLs: N-hexanoyl-l-homoserine lactone (C6-HSL, N-(3-oxo-octanoyl-l-homoserine lactone (3-oxo-C8-HSL, and N-butyryl-l-homoserine lactone (C4-HSL. This is the first report of the production of C4-HSL by H. alvei. In order to determine the relationship between the production of AHL by H. alvei H4 and bacterial growth, the β-galactosidase assay was employed to monitor AHL activity during a 48-h growth phase. AHLs production reached a maximum level of 134.6 Miller unites at late log phase (after 18 h and then decreased to a stable level of about 100 Miller unites. AHL production and bacterial growth displayed a similar trend, suggesting that growth of H. alvei H4 might be regulated by QS. The effect of AHLs on biofilm formation of H. alvei H4 was investigated by adding exogenous AHLs (C4-HSL, C6-HSL and 3-oxo-C8-HSL to H. alvei H4 culture. Biofilm formation was significantly promoted (p < 0.05 by 5 and 10 µM C6-HSL, inhibited (p < 0.05 by C4-HSL (5 and 10 µM and 5 µM 3-oxo-C8-HSL, suggesting that QS may have a regulatory role in the biofilm formation of H. alvei H4.

Presence of acylated homoserine lactones (AHLs) and AHL-producing bacteria in meat and potential role of AHL in spoilage of meat

DEFF Research Database (Denmark)

Bruhn, Jesper Bartholin; Christensen, Allan Beck; Flodgaard, Lars

2004-01-01

Quorum-sensing (QS) signals (N-acyl homoserine lactones [AHLs]) were extracted and detected from five commercially produced vacuum-packed meat samples. Ninety-six AHL-producing bacteria were isolated, and 92 were identified as Enterobacteriaceae. Hafnia alvei was the most commonly identified AHL......-producing bacterium. Thin-layer chromatographic profiles of supernatants from six H. alvei isolates and of extracts from spoiling meat revealed that the major AHL species had an R-f value and shape similar to N-3-oxo-hexanoyl homoserine lactone (OHHL). Liquid chromatography-mass spectrometry (MS) (high-resolution MS...

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

Science.gov (United States)

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC50 values of 0.44 μM (0.14 μg/mL) and 0.045 μg/mL, respectively. A semisynthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. PMID:21480509

Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms.

Science.gov (United States)

David, S; Ordway, D; Arroz, M J; Costa, J; Delgado, R

2001-01-01

The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]heptadeca-1(17),13,15-triene, abbreviated as ac3py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac3py14 and its Fe3+ 1:1 complex, [Fe(ac3py14)], inhibited radiometric growth of several strains of M. tuberculosis. Inhibition with 25 microg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac3py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis. The present study produces evidence that after stimulation with ac3py14 there was significant production of interferon gamma (IFN-gamma), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward alphabeta and gammadelta T cells and CD14+ macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses.

The specific cleavage of lactone linkage to open-loop in cyclic lipopeptide during negative ESI tandem mass spectrometry: the hydrogen bond interaction effect of 4-ethyl guaiacol.

Directory of Open Access Journals (Sweden)

Mengzhe Guo

Full Text Available Mass spectrometry is a valuable tool for the analysis and identification of chemical compounds, particularly proteins and peptides. Lichenysins G, the major cyclic lipopeptide of lichenysin, and the non-covalent complex of lichenysins G and 4-ethylguaiacol were investigated with negative ion ESI tandem mass spectrometry. The different fragmentation mechanisms for these compounds were investigated. Our study shows the 4-ethylguaiacol hydrogen bond with the carbonyl oxygen of the ester group in the loop of lichenysins G. With the help of this hydrogen bond interaction, the ring structure preferentially opens in lactone linkage rather than O-C bond of the ester-group to produce alcohol and ketene. Isothermal titration 1H-NMR analysis verified the hydrogen bond and determined the proportion of subject and ligand in the non-covalent complex to be 1∶1. Theoretical calculations also suggest that the addition of the ligand can affect the energy of the transition structures (TS during loop opening.

Microbial Stereoselective One-Step Conversion of Diols to Chiral Lactones in Yeast Cultures

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Filip Boratyński

2015-12-01

Full Text Available It has been shown that whole cells of different strains of yeast catalyze stereoselective oxidation of meso diols to the corresponding chiral lactones. Among screening-scale experiments, Candida pelliculosa ZP22 was selected as the most effective biocatalyst for the oxidation of monocyclic diols 3a–b with respect to the ratio of high conversion to stereoselectivity. This strain was used in the preparative oxidation, affording enantiomerically-enriched isomers of lactones: (+-(3aR,7aS-cis-hexahydro-1(3H -isobenzofuranone (2a and (+-(3aS,4,7,7aR-cis-tetrahydro-1(3H-isobenzofuranone (2b. Scaling up the culture growth, as well as biotransformation conditions has been successfully accomplished. Among more bulky substrates, bicyclic diol 3d was totally converted into enantiomerically-pure exo-bridged (+-(3aR,4S,7R,7aS-cis-tetrahydro-4,7-methanoisobenzofuran -1(3H-one (2d by Yarrovia lipolytica AR71. Microbial oxidation of diol 3f by Candida sake AM908 and Rhodotorula rubra AM4 afforded optically-pure cis-3-butylhexahydro-1(3H -isobenzofuranone (2f, however with low conversion.

Isolation and structural elucidation of secondary metabolites from plants of the family Flacourtiaceae and Asclepiadaceae, and evaluation of biological activity of the sesquiterpene lactones and the diterpenes of Casearia sp

International Nuclear Information System (INIS)

Binns Quiros, Franklin

2012-01-01

A phytochemical study was realized of the plants Casearia aculeata, Casearia nitida and Asclepias verticillata, using experiments of nuclear magnetic resonance (NMR) of one and two dimensions. Ten secondary metabolites are isolated from C. aculeata and C. nitida. Three of the secondary metabolites have presented a structure known: a diterpene type kaurane: ent-kaurenic acid, a diterpene type pimarane: oxide of 3β-hydroximanoil and a steroid: 4-stigmastene-3-ona. Seven remaining compounds have corresponded to diterpene type clerodane of novel structure. Eight glycosides of poly oxidized pregnanes of novel structure are isolated from A. verticillata. In vitro tests of cytotoxicity and induction of caspase-3 are performed on leukemia cells type Jurkat T. These tests were performed at fifteen sesquiterpene lactones and at four diterpenes. The tests developed have had the purpose to describe structure-activity relationships that can be linked with the capacity to inhibit the factor NF-κB (sesquiterpene lactones) described in the literature and with the known mechanism of action induction of apoptosis in diterpenes type clerodane. A clear relationship between the capacity (high, intermediate or low) to inhibit the factor NF-κB and the capacity to induce to the caspase-3 has remained without observation in the sesquiterpene lactones. Some structural comparisons related with the cytotoxic capacity and the induction of the caspase-3 have been described for the series of LSs with carbon structure of pseudoguianolides. Diterpenes with carbon structure of diterpenes type clerodane have had greater cytotoxic activity with respect to without carbon structure. Diterpenes type clerodane isolated from the family Flacourtiaceae have been cytotoxics, their capacity to induce to the caspase-3 has remained without be nearby to induction realized by the actinomycin D (pure inducer of the caspase-3). (author) [es

Dinuclear Silver(I) and Copper(II) Complexes of Hexadentate Macrocyclic Ligands Containing p-Xylyl Spacers

DEFF Research Database (Denmark)

McKenzie, Christine J.; Nielsen, Lars Preuss; Søtofte, Inger

1998-01-01

The cyclocondensation of terephthalic aldehyde with N,N-bis(3-aminopropyl)-methylamine in the presence of silver(I) gives the dinuclear tetramine Schiff base macrocyclic complex, [Ag2L1](NO3)2 (L1=7,22-N,N'-dimethyl-3,7,11,18, 22,26-hexaazatricyclo[26.2.21.18.213.16]-tetratricosa-2,11,13,15,1 7...

Application of Calixarenes as Macrocyclic Ligands for Uranium(VI: A Review

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Katarzyna Kiegiel

2013-01-01

Full Text Available Calixarenes represent a well-known family of macrocyclic molecules with broad range of potential applications in chemical, analytical, and engineering materials fields. This paper covers the use of calixarenes as complexing agents for uranium(VI. The high effectiveness of calix[6]arenes in comparison to other calixarenes in uranium(VI separation process is also presented. Processes such as liquid-liquid extraction (LLE, liquid membrane (LM separation, and ion exchange are considered as potential fields for application of calixarenes as useful agents for binding UO22+ for effective separation from aqueous solutions containing other metal components.

Macrocyclic trichothecenes are undetectable in kudzu (Pueraria montana) plants treated with a high-producing isolate of Myrothecium verrucaria.

Science.gov (United States)

Abbas, H K; Tak, H; Boyette, C D; Shier, W T; Jarvis, B B

2001-09-01

Myrothecium verrucaria was found to be an effective pathogen against kudzu grown in the greenhouse and the field. M. verrucaria produced large amounts of macrocyclic trichothecenes when cultured on solid rice medium, including epiroridin E (16.8 mg/g crude extract), epiisororidin E (1 mg/g), roridin E (8.7 mg/g), roridin H (31.3 mg/g), trichoverrin A (0.6 mg/g), trichoverrin B (0.1 mg/g), verrucarin A (37.4 mg/g), and verrucarin J (2.2 mg/g). Most of these toxins were also isolated from M. verrucaria spores and mycelia grown on potato dextrose agar medium, including epiroridin E (32.3 mg/g), epiisororidin E (28.6 mg/g), roridin E (0 mg/g), roridin H (60 mg/g), trichoverrin A (1.3 mg/g), trichoverrin B (1.8 mg/g), verrucarin A (13.8 mg/g), and verrucarin J (131 mg/g). When M. verrucaria was cultured on liquid media, the numbers but not the amounts of toxins decreased. Only epiroridin E (28.3 mg/g), epiisororidin E (29.6 mg/g), verrucarin B (195 mg/g) and verrucarin J (52.6 mg/g) were measured when the fungus was cultured on cornsteep medium. On soyflour-cornmeal broth M. verrucaria produced several toxins, including epiroridin E (58.1 mg/g), epiisororidin E (5.8 mg/g), verrucarin B (29.9 mg/g) and verrucarin J (32 mg/g). In contrast, no macrocyclic trichothecenes were detected by HPLC analysis of plant tissues of kudzu, sicklepod, and soybean treated with aqueous suspensions of M. verrucaria spores formulated with a surfactant. Chloroform-methanol extracts of kudzu leaves and stems treated with M. verrucaria spores were less cytotoxic to four cultured mammalian cell lines than the corresponding extracts from control plants. Purified macrocyclic trichothecenes (verrucarin A and T-2 toxin) were very cytotoxic to the same cell lines (< or = 2 ng/ml). These results show that neither intact macrocyclic trichothecenes nor toxic metabolites could be detected in plant tissues after treatment with M. verrucaria spores. These results argue for both safety and efficacy for the

Thermodynamic studies of the complexation of plutonium(IV) by linear and macrocyclic poly-amino-carboxylate ligands

International Nuclear Information System (INIS)

Burgat, Romain

2007-01-01

In the framework of a collaboration between the CEA (Commissariat a l Energie Atomique) of Valduc and the ICMUB (Institut de Chimie Moleculaire de l Universite de Bourgogne), a study platform of the structural and physico-chemical properties of the radioelements U, Pu and Am complexes has been implemented. The plutonium(IV) complexation has been studied in a molar nitrate medium. The affinity of three linear poly-amino-carboxylates (EDTA, CDTA and DTPA) towards plutonium(IV) has then been estimated. For the three ligands, the formation constants of the monoleptic complexes Pu(EDTA), Pu(CDTA) and [Pu(DTPA)] - have been determined in a (H,K)NO 3 1 M medium and then extrapolated at a zero ionic force with the specific interactions theory (SIT). For the three complexes, mono-hydroxylated monoleptic species have been observed. With the EDTA and the CDTA, protonated dileptic complexes of a general formula [Pu(L) 2 H h ] (4-h)- have been revealed too. Nevertheless, the steric hindrance around the metallic center is too important to allow to a second molecule of DTPA to coordinate the Pu 4+ cation. The exclusive formation of the species [Pu(DTPA)] - and [Pu(DTPA)(OH)] 2- has been confirmed by capillary electrophoresis (EC-ICP-MS). On account of the preliminary results obtained during the titration of the cyclame tetraacetic product (TETRA) in presence of plutonium(IV), the adding of a competitive ligand such as EDTA has been considered for the study of the complexation of this radioelement by macrocyclic ligands. At last, the affinity of different macrocyclic ligands containing either four amide functions (TETAMMe 2 and TETAMMEt 2 ) or carboxylate groups (TETA, DOTPr and TETPr) towards lanthanides(III) has been estimated too. Although the complexation reaction be fast with the two first ligands, these complexes are less stable than those formed with the carboxylic macrocycles. (O.M.)

N-acyl-homoserine lactone uptake and systemic transport in barley rest upon active parts of the plant

Czech Academy of Sciences Publication Activity Database

Sieper, T.; Forczek, Sándor; Matucha, Miroslav; Kraemer, P.; Hartmann, A.; Schroeder, P.

2014-01-01

Roč. 201, č. 2 (2014), s. 545-555 ISSN 1469-8137 Institutional support: RVO:61389030 Keywords : barley (Hordeum vulgare) * monoclonal antibodies * N-acyl-homoserine lactones (HSLs) Subject RIV: EF - Botanics Impact factor: 6.545, year: 2013

Effect of sequential fermentations and grape cultivars on volatile compounds and sensory profiles of Danish wines

DEFF Research Database (Denmark)

Liu, Jing; Arneborg, Nils; Toldam-Andersen, Torben

2017-01-01

BACKGROUND: There has been an increasing interest in the use of selected non-Saccharomyces yeasts in co-culture with Saccharomyces cerevisiae. In this work, three non-Saccharomyces yeast strains (Metschnikowia viticola, Metschnikowia fructicola and Hanseniaspora uvarum) indigenously isolated...... in Denmark were used in sequential fermentations with S. cerevisiae on three cool-climate grape cultivars, Bolero, Rondo and Regent. During the fermentations, the yeast growth was determined as well as key oenological parameters, volatile compounds and sensory properties of finished rosé wines. RESULTS......: The different non-Saccharomyces strains and cool-climate grape cultivars produced wines with a distinctive aromatic profile. A total of 67 volatile compounds were identified, including 43 esters, 14 alcohols, five acids, two ketones, a C13-norisoprenoid, a lactone and a sulfur compound. The use of M. viticola...

Unusual nanosized associates of carboxy-calix[4]resorcinarene and cetylpyridinium chloride: the macrocycle as a glue for surfactant micelles.

Science.gov (United States)

Morozova, Ju E; Syakaev, V V; Shalaeva, Ya V; Ermakova, A M; Nizameev, I R; Kadirov, M K; Voloshina, A D; Zobov, V V; Antipin, I S; Konovalov, A I

2017-03-08

The association of cetylpyridinium chloride (CPC) micelles in the presence of octaacetated tetraphenyleneoxymethylcalix[4]resorcinarene (CR) leads to the formation of unusual spherical supramolecular nanoparticles (SNPs). Within the range of CR/CPC molar ratios from 10/1 to 1/10 (except for 1/8), CR, acting as a counterion, decreases the critical micelle concentration of CPC by one order of magnitude and leads to the formation of SNPs with an average hydrodynamic radius of 164 nm and an average zeta potential of -60 mV. The formation of SNPs was studied by NMR FT-PGSE and 2D NOESY, DLS, TEM, fluorimetry, and UV-Vis methods. The stability of SNPs at different temperatures and pH values and in the presence of electrolytes was investigated. The specificity of the interactions of the SNPs with substrates that were preferentially bound by a macrocycle or CPC micelle was studied. The enhancement of cation dye binding in the presence of SNPs is shown. The presented supramolecular system may serve as a nanocapsule for water-soluble and water-insoluble compounds.

Cocomplexation of urea and UO22+ in a Schiff base macrocycle: a mimic of an enzyme binding site

International Nuclear Information System (INIS)

van Staveren, C.J.; Fenton, D.E.; Reinhoudt, D.N.; van Eerden, J.; Harkema, S.

1987-01-01

As part of the authors work on the complexation of neutral molecules by macrocyclic ligands, they are particularly interested in the complexation of urea. They have shown that urea can form complexes with (aza-)18-crown but the association constants of these complexes in water are very small (18-crown-6-urea, log K/sub s/ = 0.1). Protonation of urea effects stronger binding especially when the crown ether is sufficiently large to form an encapsulated complex (e.g., the complex benzo-27-crown-9-urea-HClO 4 ). Protonation of the weakly basic urea (pK/sub a/ = 0.1, water, 25 0 C) requires strongly acidic conditions and to avoid this they have introduced a covalently linked carboxylic group in the cavity of the macrocycle. A strong hydrogen bond of urea with 2-carboxyl-1,3-xylyl-30-crown-9 results in an encapsulated complex. The concept of using an electrophilic center to bind urea in the cavity of a crown ether proved to be a more general concept. A metal cation can serve as the electrophile as was shown by the isolation and single-crystal X-ray analysis of the 2,6-pyrido-27-crown-9-urea-LiClO 4 (1:2:1) complex in which one of the urea molecules is encapsulated. In an effort to bind an electrophilic metal ion in the crown ethers irreversibly they have concentrated their work on macrocycles of type 1, since the strong binding of quadridentate (salen type) Schiff bases with soft metal ions is well-known

(1S-1,2-O-Benzylidene-α-d-glucurono-6,3-lactone

Directory of Open Access Journals (Sweden)

David J. Watkin

2009-02-01

Full Text Available X-ray crystallographic analysis has established that the major product from the protection of d-glucoronolactone with benzaldehyde is (1S-1,2-O-benzylidene-α-d-glucurono-6,3-lactone, C13H12O6, rather than the R epimer. The crystal structure exists as O—H...O hydrogen-bonded chains of molecules lying parallel to the a axis. The absolute configuration was determined by the use of d-glucuronolactone as the starting material.

Second symposium on macrocyclic compounds

International Nuclear Information System (INIS)

Izatt, R.M.; Christensen, J.J.

1978-01-01

Forty papers were presented at the sumposium under five session headings: inorganic reactions, industrial applications, biological and biochemistry, organic synthesis and reactions, and thermodynamics and kinetics. Abstracts of these papers are included in this document

Antiplasmodial activities and cytotoxic effects of aqueous extracts and sesquiterpene lactones from Neurolaena lobata.

Science.gov (United States)

François, G; Passreiter, C M; Woerdenbag, H J; Van Looveren, M

1996-04-01

Aqueous and lipophilic extracts of Neurolaena lobata (Asteraceae), obtained from Guatemala, were tested against Plasmodium falciparum in vitro. Moreover, sesquiterpene lactones, of the germacranolide and furanoheliangolide type, isolated from N. lobata, were shown to be active against P. falciparum in vitro. In addition to their antiplasmodial activity, their cytotoxic effects on human carcinoma cell lines were evaluated. Structure-activity relationships are discussed.

Antiproliferative compounds of Cyphostemma greveana from a Madagascar dry forest.

Science.gov (United States)

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

2011-04-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 μM (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

O-Succinyl-L-homoserine-based C4-chemical production: succinic acid, homoserine lactone, γ-butyrolactone, γ-butyrolactone derivatives, and 1,4-butanediol.

Science.gov (United States)

Hong, Kuk-Ki; Kim, Jeong Hyun; Yoon, Jong Hyun; Park, Hye-Min; Choi, Su Jin; Song, Gyu Hyeon; Lee, Jea Chun; Yang, Young-Lyeol; Shin, Hyun Kwan; Kim, Ju Nam; Cho, Kyung Ho; Lee, Jung Ho

2014-10-01

There has been a significant global interest to produce bulk chemicals from renewable resources using engineered microorganisms. Large research programs have been launched by academia and industry towards this goal. Particularly, C4 chemicals such as succinic acid (SA) and 1,4-butanediol have been leading the path towards the commercialization of biobased technology with the effort of replacing chemical production. Here we present O-Succinyl-L-homoserine (SH) as a new, potentially important platform biochemical and demonstrate its central role as an intermediate in the production of SA, homoserine lactone (HSL), γ-butyrolactone (GBL) and its derivatives, and 1,4-butanediol (BDO). This technology encompasses (1) the genetic manipulation of Escherichia coli to produce SH with high productivity, (2) hydrolysis into SA and homoserine (HS) or homoserine lactone hydrochloride, and (3) chemical conversion of either HS or homoserine lactone HCL (HSL·HCl) into drop-in chemicals in polymer industry. This production strategy with environmental benefits is discussed in the perspective of targeting of fermented product and a process direction compared to petroleum-based chemical conversion, which may reduce the overall manufacturing cost.

Optical spectra of phthalocyanines and related compounds a guide for beginners

CERN Document Server

Isago, Hiroaki

2015-01-01

This book displays how optical (absorption, emission, and magnetic circular dichroism) spectra of phthalocyanines and related macrocyclic dyes can be varied from their prototypical ones depending on conditions. As these compounds can be involved in colorful chemistry (which might be driven by impurities in solvents), their spectra behave like the sea-god Proteus in their mutability. Therefore, those who have been engaged with phthalocyanines for the first time, including even educated professional researchers and engineers, may have been embarrassed by the deceptive behavior of their compounds and could have, in the worst cases, given up their projects. This book is aimed not merely at reviewing the optical spectra, but also at helping such people, particularly beginners, to figure them out by showing some examples of their prototypical spectra and their variations in several situations. For the purpose of better understanding, the book also provides an introduction to their theoretical backgrounds as graphic...

Neighbor-directed histidine N(τ) alkylation. A route to imidazolium-containing phosphopeptide macrocycles

Energy Technology Data Exchange (ETDEWEB)

Qian, Wen-Jian [National Cancer Inst., Frederick, MD (United States); Park, Jung-Eun [National Cancer Inst., Bethesda, MD (United States); Grant, Robert [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lai, Christopher C. [National Cancer Inst., Frederick, MD (United States); Kelley, James A. [National Cancer Inst., Frederick, MD (United States); Yaffe, Michael B. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Lee, Kyung S. [National Cancer Inst., Bethesda, MD (United States); Burke, Terrence R. [National Cancer Inst., Frederick, MD (United States)

2015-07-07

Our recently discovered, selective, on-resin route to N(τ)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. These cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation. Furthermore, neighbor-directed histidine N(τ)-alkylation opens the door to new families of phosphopeptidomimetics for use in a range of chemical biology contexts.

Layer chromatography-bioassays directed screening and identification of antibacterial compounds from Scotch thistle.

Science.gov (United States)

Móricz, Ágnes M; Krüzselyi, Dániel; Alberti, Ágnes; Darcsi, András; Horváth, Györgyi; Csontos, Péter; Béni, Szabolcs; Ott, Péter G

2017-11-17

The antibacterial profiling of Onopordum acanthium L. leaf extract and subsequent targeted identification of active compounds is demonstrated. Thin-layer chromatography (TLC) and off-line overpressured layer chromatography (OPLC) coupled with direct bioautography were utilized for investigation of the extract against eight bacterial strains including two plant and three human pathogens and a soil, a marine and a probiotic human gut bacteria. Antibacterial fractions obtaining infusion-transfusion OPLC were transferred to HPLC-MS/MS analysis that resulted in the characterization of three active compounds and two of them were identified as, linoleic and linolenic acid. OPLC method was adopted to preparative-scale flash chromatography for the isolation of the third active compound, which was identified after a further semi-preparative HPLC purification as the germacranolide sesquiterpene lactone onopordopicrin. Pure onopordopicrin exhibited antibacterial activity that was specified as minimal inhibitory concentration in the liquid phase as well. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and characterization of two new tetrapyrazolic macrocycles for the selective extraction of cesium cation

Czech Academy of Sciences Publication Activity Database

Harit, T.; Malek, F.; El Bali, B.; Dušek, Michal; Kučeráková, Monika

2016-01-01

Roč. 72, č. 27-28 (2016), s. 3966-3973 ISSN 0040-4020 R&D Projects: GA MŠk LO1603; GA ČR(CZ) GA14-03276S EU Projects: European Commission(XE) CZ.2.16/3.1.00/24510 Institutional support: RVO:68378271 Keywords : cesium cation * liquid–liquid extraction * macrocycle * pyrazole * crystal structure Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.651, year: 2016

Lead Diversification through a Prins-Driven Macrocyclization Strategy: Application to C13-Diversified Bryostatin Analogues.

Science.gov (United States)

Wender, Paul A; Billingsley, Kelvin L

2013-01-01

The design, synthesis, and biological evaluation of a novel class of C13-diversified bryostatin analogues are described. An innovative and general strategy based on a Prins macrocyclization-nucleophilic trapping cascade was used to achieve late-stage diversification. In vitro analysis of selected library members revealed that modification at the C13 position of the bryostatin scaffold can be used as a diversification handle to regulate biological activity.

Template synthesis of poly aza macrocyclic copper(II) and nickel(II) complexes: Spectral characterization and antimicrobial studies

Energy Technology Data Exchange (ETDEWEB)

Gurumoorthy, P.; Ravichandran, J.; Kaliur Rahiman, A. [The New College, Chennai (India); Karthikeyan, N.; Palani, P. [Univ. of Madras, Chennai (India)

2012-07-15

The template synthesis of copper(II) and nickel(II) complexes derived from 2,6-diformyl-4-methylphenol with diethylenetriamine or 1,2-bis(3-amino propylamino)ethane produce the 12-membered N{sub 3}O and 17-membered N{sub 4}O macrocyclic complexes, respectively. The geometry of the complexes has been determined with the help of electronic and EPR spectroscopic values and found to be five coordinated square pyramidal and, six coordinated distorted tetragonal for 12-membered and 17-membered macrocyclic complexes, respectively. Electrochemical studies of the mononuclear N{sub 3}O and N{sub 4}O copper(II) complexes show one irreversible one electron reduction wave at E{sup pc} = .1.35 and .1.15 V respectively, and the corresponding nickel(II) complexes show irreversible one-electron reduction wave at E{sup pc} = .1.25 and .1.22 V, respectively. The nickel(II) complexes show irreversible one-electron oxidation wave at Epa = +0.84 and +0.82 V, respectively. All the complexes were evaluated for in vitro antimicrobial activity against the human pathogenic bacteria and fungi.

Recent results of examination of the applicability of polyoxonium compounds to the extraction separation of rare earth elements

International Nuclear Information System (INIS)

Buchalova, M.

1992-01-01

Macrocyclic polyethers possess an extraordinary ability to bond with high selectivity to metal ions. The salt-polyether complex is formed by ion-dipole interaction between the cation and the negatively charged oxygen atoms symmetrically positioned in the polyether ring. Compounds of cyclic polyethers can be employed as extractants in solvent extraction systems, which not only can be applied to the separation of ions but also can provide information on the mechanism of the complexation. The process of extraction of lanthanides in the presence of hydrophobic counter-ions is described, and the calculated equilibrium constants are given. A survey is presented of the application of polyoxonium compounds to the extraction separation of rare earths. (M.D.). 12 figs., 3 tabs., 40 refs

Evaluating the mutagenic potential of aerosol organic compounds using informatics-based screening

Science.gov (United States)

Decesari, Stefano; Kovarich, Simona; Pavan, Manuela; Bassan, Arianna; Ciacci, Andrea; Topping, David

2018-02-01

Whilst general policy objectives to reduce airborne particulate matter (PM) health effects are to reduce exposure to PM as a whole, emerging evidence suggests that more detailed metrics associating impacts with different aerosol components might be needed. Since it is impossible to conduct toxicological screening on all possible molecular species expected to occur in aerosol, in this study we perform a proof-of-concept evaluation on the information retrieved from in silico toxicological predictions, in which a subset (N = 104) of secondary organic aerosol (SOA) compounds were screened for their mutagenicity potential. An extensive database search showed that experimental data are available for 13 % of the compounds, while reliable predictions were obtained for 82 %. A multivariate statistical analysis of the compounds based on their physico-chemical, structural, and mechanistic properties showed that 80 % of the compounds predicted as mutagenic were grouped into six clusters, three of which (five-membered lactones from monoterpene oxidation, oxygenated multifunctional compounds from substituted benzene oxidation, and hydroperoxides from several precursors) represent new candidate groups of compounds for future toxicological screenings. These results demonstrate that coupling model-generated compositions to in silico toxicological screening might enable more comprehensive exploration of the mutagenic potential of specific SOA components.

Dysprosium complexes with the tetraphenylporphyrin macrocyclic ligand; Complejos de disprosio con el ligante macrociclico tetrafenilporfirina

Energy Technology Data Exchange (ETDEWEB)

Martinez M, V.; Padilla, J.; Ramirez, F.M

1992-04-15

In this report, the results obtained on the synthesis, characterization and study of the chemical behavior of dysprosium complex with the acetylacetone chelating agent (Hacac) and the tetraphenylporphyrin macrocyclic ligand (H{sub 2}TFP) are given. Based on the literature but according to our necessities and interest, the appropriate methodology settled down from the synthesis of prime matters until the obtaining and characterization of the products. The acetyl acetonate complex was obtained of mono hydrated dysprosium [Dy(acac){sub 3}. H{sub 2}0] and trihydrated [Dy(acac){sub 3} .3 H{sub 2}0], the mono tetra phenyl porphyrinate [Dy(TFP)(acac). 2 ac] the double sandwich of the dysprosium porphyrinate [Dy(TFP){sub 2}] and the triple sandwich of the dysprosium porphyrinate [Dy(TFP){sub 3}. 2 TCB] (TCB = trichlorobenzene). Its were characterized by their melting points, solubility, IR, UV, TGA and DTA both first and besides the techniques already mentioned for NMR'H, RPE and Magnetic susceptibility the three last complexes. From the spectroscopic point of view, IR and RPE its suggested the existence of a complex of inverse mixed valence [Dy(TFP){sup 2-} (TFP) {sup 1-}] for the Dy(TFP){sub 2} as a result of the existence of the free radical (TFP' {sup 1-} and that it was not in none of the other porphyrin compounds. In the NMR'H spectra of the compounds were not observed signals in the region from 0 to 10 ppm that which shows that the dysprosium complexes in special those of the porphyrin type are highly paramagnetic and its could be used as displacement reagents, creators of images and contrast agents of great utility in these days in studies of NMR, technique today by today used in medical diagnoses. (Author)

Dysprosium complexes with the tetraphenylporphyrin macrocyclic ligand; Complejos de disprosio con el ligante macrociclico tetrafenilporfirina

Energy Technology Data Exchange (ETDEWEB)

Martinez M, V; Padilla, J; Ramirez, F M

1992-04-15

In this report, the results obtained on the synthesis, characterization and study of the chemical behavior of dysprosium complex with the acetylacetone chelating agent (Hacac) and the tetraphenylporphyrin macrocyclic ligand (H{sub 2}TFP) are given. Based on the literature but according to our necessities and interest, the appropriate methodology settled down from the synthesis of prime matters until the obtaining and characterization of the products. The acetyl acetonate complex was obtained of mono hydrated dysprosium [Dy(acac){sub 3}. H{sub 2}0] and trihydrated [Dy(acac){sub 3} .3 H{sub 2}0], the mono tetra phenyl porphyrinate [Dy(TFP)(acac). 2 ac] the double sandwich of the dysprosium porphyrinate [Dy(TFP){sub 2}] and the triple sandwich of the dysprosium porphyrinate [Dy(TFP){sub 3}. 2 TCB] (TCB = trichlorobenzene). Its were characterized by their melting points, solubility, IR, UV, TGA and DTA both first and besides the techniques already mentioned for NMR'H, RPE and Magnetic susceptibility the three last complexes. From the spectroscopic point of view, IR and RPE its suggested the existence of a complex of inverse mixed valence [Dy(TFP){sup 2-} (TFP) {sup 1-}] for the Dy(TFP){sub 2} as a result of the existence of the free radical (TFP' {sup 1-} and that it was not in none of the other porphyrin compounds. In the NMR'H spectra of the compounds were not observed signals in the region from 0 to 10 ppm that which shows that the dysprosium complexes in special those of the porphyrin type are highly paramagnetic and its could be used as displacement reagents, creators of images and contrast agents of great utility in these days in studies of NMR, technique today by today used in medical diagnoses. (Author)

Green chemistry for preparation of oligopyrrole macrocycles precursors: Novel methodology for dipyrromethanes and tripyrromethanes synthesis in water

Czech Academy of Sciences Publication Activity Database

Král, Vladimír; Vašek, P.; Dolenský, B.

2004-01-01

Roč. 69, č. 5 (2004), s. 1126-1136 ISSN 0010-0765 R&D Projects: GA ČR GA203/02/0933; GA ČR GA203/02/0420; GA ČR GP203/03/D049 Grant - others:QLRT(XE) 2000-02360 Keywords : oligopyrrole macrocycles * porphyrins * calixpyrrols Subject RIV: CC - Organic Chemistry Impact factor: 1.062, year: 2004

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

Directory of Open Access Journals (Sweden)

Stefanie Zimmermann

2014-03-01

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

A Biologically Active Analog of the Sex Pheromone of the Emerald Ash Borer, Agrilus planipennis.

Science.gov (United States)

Silk, P J; Ryall, K; Mayo, P; MaGee, D I; Leclair, G; Fidgen, J; Lavallee, R; Price, J; McConaghy, J

2015-03-01

The emerald ash borer, Agrilus planipennis (Coleoptera: Buprestidae) (EAB), is an invasive species causing unprecedented levels of mortality to ash trees in its introduced range. The female-produced sex pheromone of EAB has been shown to contain the macrocyclic lactone (3Z)-dodecen-12-olide. This compound and its geometrical isomer, (3E)-dodecen-12-olide, have been demonstrated previously to be EAG active and, in combination with a host-derived green leaf volatile, (3Z)-hexenol, to be attractive to male EAB in green prism traps deployed in the ash tree canopy. In the current study, we show that the saturated analog, dodecan-12-olide, is similarly active, eliciting an antennal response and significant attraction of EAB in both olfactometer and trapping bioassays in green traps with (3Z)-hexenol. Conformational modeling of the three lactones reveals that their energies and shapes are very similar, suggesting they might share a common receptor in EAB antennae. These findings provide new insight into the pheromone ecology of this species, highlighting the apparent plasticity in response of adults to the pheromone and its analog. Both of the unsaturated isomers are costly to synthesize, involving multistep, low-yielding processes. The saturated analog can be made cheaply, in high yield, and on large scale via Mitsunobu esterification of a saturated ω-hydroxy acid or more simply by Baeyer-Villiger oxidation of commercially available cyclododecanone. The analog can thus provide an inexpensive option as a lure for detection surveys as well as for possible mitigation purposes, such as mating disruption.

Sesquiterpene lactones and monoterpene glucosides from plant species Picris echoides

Directory of Open Access Journals (Sweden)

MILUTIN STEFANOVIC

2000-11-01

Full Text Available Investigation of the constituents of the aerial parts of domestic plant species Picris echoides afforded the sesquiterpene lactones, i.e., guaianolides jacquilenin (1, 11-epi-jacquilenin (2, achillin (3 and eudesmanolide telekin (4. The chemical indentification of the two monoterpene glucosides (–-cis-chrysanthenol-b-D-glucopyranoside (5 and its 6’-acetate 6 is also repoted. The guaianolide achillin (3 and the two monoterpene glucosides 5 and 6 were isolated for the first time from this plant species. Isolation was achieved by column chromatography and the structures were established mainly by the interpretation of their physical and spectral data, which were in agreement with those in the literature.

Exploring Anti-Bacterial Compounds against Intracellular Legionella

Science.gov (United States)

Harrison, Christopher F.; Kicka, Sébastien; Trofimov, Valentin; Berschl, Kathrin; Ouertatani-Sakouhi, Hajer; Ackermann, Nikolaus; Hedberg, Christian; Cosson, Pierre; Soldati, Thierry; Hilbi, Hubert

2013-01-01

Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an ‘accidental’ human pathogen and cause a severe pneumonia known as Legionnaires’ disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoeba castellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target. PMID:24058631

Exploring anti-bacterial compounds against intracellular Legionella.

Directory of Open Access Journals (Sweden)

Christopher F Harrison

Full Text Available Legionella pneumophila is a ubiquitous fresh-water bacterium which reproduces within its erstwhile predators, environmental amoeba, by subverting the normal pathway of phagocytosis and degradation. The molecular mechanisms which confer resistance to amoeba are apparently conserved and also allow replication within macrophages. Thus, L. pneumophila can act as an 'accidental' human pathogen and cause a severe pneumonia known as Legionnaires' disease. The intracellular localisation of L. pneumophila protects it from some antibiotics, and this fact must be taken into account to develop new anti-bacterial compounds. In addition, the intracellular lifestyle of L. pneumophila may render the bacteria susceptible to compounds diminishing bacterial virulence and decreasing intracellular survival and replication of this pathogen. The development of a single infection cycle intracellular replication assay using GFP-producing L. pneumophila and Acanthamoebacastellanii amoeba is reported here. This fluorescence-based assay allows for continuous monitoring of intracellular replication rates, revealing the effect of bacterial gene deletions or drug treatment. To examine how perturbations of the host cell affect L. pneumophila replication, several known host-targeting compounds were tested, including modulators of cytoskeletal dynamics, vesicle scission and Ras GTPase localisation. Our results reveal a hitherto unrealized potential antibiotic property of the β-lactone-based Ras depalmitoylation inhibitor palmostatin M, but not the closely related inhibitor palmostatin B. Further characterisation indicated that this compound caused specific growth inhibition of Legionella and Mycobacterium species, suggesting that it may act on a common bacterial target.

Analysis of volatile compounds from Iberian hams: a review

Directory of Open Access Journals (Sweden)

Narváez-Rivas, M.

2012-10-01

Full Text Available This article provides information on the study of the volatile compounds in raw and dry-cured Iberian hams. Different volatile compounds are identified and studies carried out by different authors are presented. This article reviews the analytical methods that have been used to determine the different volatiles of these samples. Furthermore, all volatile compounds identified (a total of 411 volatiles have been collected in several tables according to different series of compounds: hydrocarbons, aldehydes, ketones, alcohols, esters and ethers, lactones, terpenes and chloride compounds, nitrogenous compounds, sulfur compounds and carboxylic acids. This review can be useful in subsequent research due to the complexity of the study.

En este artículo se proporciona información sobre el estudio de los compuestos volátiles del jamón ibérico tanto fresco como curado. Se presentan los diferentes compuestos volátiles identificados por distintos autores. Además, se evalúan los métodos analíticos que han sido utilizados para determinar dichos compuestos volátiles en este tipo de muestras. Todos los compuestos identificados y descritos en esta revisión (un total de 411 compuestos volátiles han sido agrupados en diversas tablas de acuerdo a las diferentes familias a que pertenecen: hidrocarburos, aldehídos, cetonas, alcoholes, ésteres y éteres, lactonas, terpenos, compuestos halogenados, compuestos nitrogenados, compuestos de azufre y ácidos carboxílicos. Debido a la complejidad de este estudio, la presente revisión puede ser muy útil en investigaciones posteriores.

Molecular identification of tuliposide B-converting enzyme: a lactone-forming carboxylesterase from the pollen of tulip.

Science.gov (United States)

Nomura, Taiji; Murase, Tatsunori; Ogita, Shinjiro; Kato, Yasuo

2015-07-01

6-Tuliposides A (PosA) and B (PosB), which are the major secondary metabolites in tulip (Tulipa gesneriana), are enzymatically converted to the antimicrobial lactonized aglycons, tulipalins A (PaA) and B (PaB), respectively. We recently identified a PosA-converting enzyme (TCEA) as the first reported member of the lactone-forming carboxylesterases. Herein, we describe the identification of another lactone-forming carboxylesterase, PosB-converting enzyme (TCEB), which preferentially reacts with PosB to give PaB. This enzyme was isolated from tulip pollen, which showed high PosB-converting activity. Purified TCEB exhibited greater activity towards PosB than PosA, which was contrary to that of the TCEA. Novel cDNA (TgTCEB1) encoding the TCEB was isolated from tulip pollen. TgTCEB1 belonged to the carboxylesterase family and was approximately 50% identical to the TgTCEA polypeptides. Functional characterization of the recombinant enzyme verified that TgTCEB1 catalyzed the conversion of PosB to PaB with an activity comparable with the native TCEB. RT-qPCR analysis of each part of plant revealed that TgTCEB1 transcripts were limited almost exclusively to the pollen. Furthermore, the immunostaining of the anther cross-section using anti-TgTCEB1 polyclonal antibody verified that TgTCEB1 was specifically expressed in the pollen grains, but not in the anther cells. N-terminal transit peptide of TgTCEB1 was shown to function as plastid-targeted signal. Taken together, these results indicate that mature TgTCEB1 is specifically localized in plastids of pollen grains. Interestingly, PosB, the substrate of TgTCEB1, accumulated on the pollen surface, but not in the intracellular spaces of pollen grains. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

[Tl(III)(dota)](-): An Extraordinarily Robust Macrocyclic Complex.

Science.gov (United States)

Fodor, Tamás; Bányai, István; Bényei, Attila; Platas-Iglesias, Carlos; Purgel, Mihály; Horváth, Gábor L; Zékány, László; Tircsó, Gyula; Tóth, Imre

2015-06-01

The X-ray structure of {C(NH2)3}[Tl(dota)]·H2O shows that the Tl(3+) ion is deeply buried in the macrocyclic cavity of the dota(4-) ligand (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) with average Tl-N and Tl-O distances of 2.464 and 2.365 Å, respectively. The metal ion is directly coordinated to the eight donor atoms of the ligand, which results in a twisted square antiprismatic (TSAP') coordination around Tl(3+). A multinuclear (1)H, (13)C, and (205)Tl NMR study combined with DFT calculations confirmed the TSAP' structure of the complex in aqueous solution, which exists as the Λ(λλλλ)/Δ(δδδδ) enantiomeric pair. (205)Tl NMR spectroscopy allowed the protonation constant associated with the protonation of the complex according to [Tl(dota)](-) + H(+) ⇆ [Tl(Hdota)] to be determined, which turned out to be pK(H)Tl(dota) = 1.4 ± 0.1. [Tl(dota)](-) does not react with Br(-), even when using an excess of the anion, but it forms a weak mixed complex with cyanide, [Tl(dota)](-) + CN(-) ⇆ [Tl(dota)(CN)](2-), with an equilibrium constant of Kmix = 6.0 ± 0.8. The dissociation of the [Tl(dota)](-) complex was determined by UV-vis spectrophotometry under acidic conditions using a large excess of Br(-), and it was found to follow proton-assisted kinetics and to take place very slowly (∼10 days), even in 1 M HClO4, with the estimated half-life of the process being in the 10(9) h range at neutral pH. The solution dynamics of [Tl(dota)](-) were investigated using (13)C NMR spectroscopy and DFT calculations. The (13)C NMR spectra recorded at low temperature (272 K) point to C4 symmetry of the complex in solution, which averages to C4v as the temperature increases. This dynamic behavior was attributed to the Λ(λλλλ) ↔ Δ(δδδδ) enantiomerization process, which involves both the inversion of the macrocyclic unit and the rotation of the pendant arms. According to our calculations, the arm-rotation process limits the Λ(λλλλ) ↔ �

Anthelmintic activity of chicory (Cichorium intybus): in vitro effects on swine nematodes and relationship to sesquiterpene lactone composition

DEFF Research Database (Denmark)

Williams, Andrew; Pena-Espinoza, Miguel Angel; Boas, Ulrik

2016-01-01

of a specific anthelmintic effect rather than generalized toxicity. Ultra-high liquid chromatography-mass spectrometry analysis revealed that the purified extracts were rich in sesquiterpene lactones (SL), and that the SL profile differed significantly between cultivars. This is the first report of anthelmintic...

Characterization of N-acylhomoserine lactone-degrading bacteria associated with the Zingiber officinale (ginger rhizosphere: Co-existence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia

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Chhabra Siri

2011-03-01

Full Text Available Abstract Background Cell-to-cell communication (quorum sensing (QS co-ordinates bacterial behaviour at a population level. Consequently the behaviour of a natural multi-species community is likely to depend at least in part on co-existing QS and quorum quenching (QQ activities. Here we sought to discover novel N-acylhomoserine lactone (AHL-dependent QS and QQ strains by investigating a bacterial community associated with the rhizosphere of ginger (Zingiber officinale growing in the Malaysian rainforest. Results By using a basal growth medium containing N-(3-oxohexanoylhomoserine lactone (3-oxo-C6-HSL as the sole source of carbon and nitrogen, the ginger rhizosphere associated bacteria were enriched for strains with AHL-degrading capabilities. Three isolates belonging to the genera Acinetobacter (GG2, Burkholderia (GG4 and Klebsiella (Se14 were identified and selected for further study. Strains GG2 and Se14 exhibited the broadest spectrum of AHL-degrading activities via lactonolysis while GG4 reduced 3-oxo-AHLs to the corresponding 3-hydroxy compounds. In GG2 and GG4, QQ was found to co-exist with AHL-dependent QS and GG2 was shown to inactivate both self-generated and exogenously supplied AHLs. GG2, GG4 and Se14 were each able to attenuate virulence factor production in both human and plant pathogens. Conclusions Collectively our data show that ginger rhizosphere bacteria which make and degrade a wide range of AHLs are likely to play a collective role in determining the QS-dependent phenotype of a polymicrobial community.

Sesquiterpene lactones. XXXIII. Guaianolides in the subgenus Psephellus (Cass. Schmalh., genus Centaurea L.

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Gerard Nowak

2014-01-01

Full Text Available Sesquiterpene lactones were found to occur in all of the studied species of the subgenus Psephellus (Cass. Schmalh. Differing compositions were found in the representatives of three sections. In Centaurea declinata MB. from the section Leucophylle (Sosn. Sosn.. 15-deoxyrepin, linichlorin B and cynaropicrin were found. Linichlorin B dominated in Centaurea hypoleucu DC. from section Hypoleucae (Sosn. Sosn., while in the species classified in section Psephellus Sosn., repin, acroptilin, jenerin, centaurepensin and, in some, also cynaropicrin. dominated.

HIGH PERFORMANCE LIQUID CHROMATOGRAPHY USE IN ANALYSIS OF SESQUITERPENIC LACTONES OF LAURUS NOBILIS

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S. P. Senchenko

2015-01-01

Full Text Available We have developed a methodology of quantitative determination of sesquiterpenic lactones (costunolide and dehydrocostuslactone in leaves of Laurus nobilis using reversed phase HPLC. We have determined optimal conditions for the substances under study extraction from active parts. Using the developed methods we have established that costunolide and dehydrocostuslactone content in Laurus nobilis samples in terms of absolutely dry active parts is 0.99 and 0.26% correspondingly.

Virtual libraries of tetrapyrrole macrocycles. Combinatorics, isomers, product distributions, and data mining.

Science.gov (United States)

Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S

2011-09-26

A software program (PorphyrinViLiGe) has been developed to enumerate the type and relative amounts of substituted tetrapyrrole macrocycles in a virtual library formed by one of four different classes of reactions. The classes include (1) 4-fold reaction of n disubstituted heterocycles (e.g., pyrroles or diiminoisoindolines) to form β-substituted porphyrins, β-substituted tetraazaporphyrins, or α- or β-substituted phthalocyanines; (2) combination of m aminoketones and n diones to form m × n pyrroles, which upon 4-fold reaction give β-substituted porphyrins; (3) derivatization of an 8-point tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and pyrrole to form meso-substituted porphyrins. The program accommodates variable ratios of reactants, reversible or irreversible reaction (reaction classes 1 and 2), and degenerate modes of formation. Pólya's theorem (for enumeration of cyclic entities) has also been implemented and provides validation for reaction classes 3 and 4. The output includes the number and identity of distinct reaction-accessible substituent combinations, the number and identity of isomers thereof, and the theoretical mass spectrum. Provisions for data mining enable assessment of the number of products having a chosen pattern of substituents. Examples include derivatization of an octa-substituted phthalocyanine with eight reagents to afford a library of 2,099,728 members (yet only 6435 distinct substituent combinations) and reversible reaction of six distinct disubstituted pyrroles to afford 2649 members (yet only 126 distinct substituent combinations). In general, libraries of substituted tetrapyrrole macrocycles occupy a synthetically accessible region of chemical space that is rich in isomers (>99% or 95% for the two examples, respectively).

Macrocyclic peptide inhibitors for the protein-protein interaction of Zaire Ebola virus protein 24 and karyopherin alpha 5.

Science.gov (United States)

Song, Xiao; Lu, Lu-Yi; Passioura, Toby; Suga, Hiroaki

2017-06-21

Ebola virus infection leads to severe hemorrhagic fever in human and non-human primates with an average case fatality rate of 50%. To date, numerous potential therapies are in development, but FDA-approved drugs or vaccines are yet unavailable. Ebola viral protein 24 (VP24) is a multifunctional protein that plays critical roles in the pathogenesis of Ebola virus infection, e.g. innate immune suppression by blocking the interaction between KPNA and PY-STAT1. Here we report macrocyclic peptide inhibitors of the VP24-KPNA5 protein-protein interaction (PPI) by means of the RaPID (Random non-standard Peptides Integrated Discovery) system. These macrocyclic peptides showed remarkably high affinity to recombinant Zaire Ebola virus VP24 (eVP24), with a dissociation constant in the single digit nanomolar range, and could also successfully disrupt the eVP24-KPNA interaction. This work provides for the first time a chemical probe capable of modulating this PPI interaction and is the starting point for the development of unique anti-viral drugs against the Ebola virus.

Divergent Synthesis of Revised Apratoxin E, 30-epi-Apratoxin E, and 30S/30R-Oxoapratoxin E.

Science.gov (United States)

Mao, Zhuo-Ya; Si, Chang-Mei; Liu, Yi-Wen; Dong, Han-Qing; Wei, Bang-Guo; Lin, Guo-Qiang

2017-10-20

In this report, originally proposed apratoxin E (30S-7), revised apratoxin E (30R-7), and (30S)/(30R)-oxoapratoxin E (30S)-38/(30R)-38 were efficiently prepared by two synthetic methods. The chiral lactone 10, recycled from the degradation of saponin glycosides, was utilized to prepare the key nonpeptide fragment 9. Our alternative convergent assembly strategy was applied to the divergent synthesis of revised apratoxin E and its three analogues. Moreover, ring-closing metathesis (RCM) was for the first time found to be an efficient strategy for the macrocyclization of apratoxins.

Identification and characterization of an N-acylhomoserine lactone-dependent quorum-sensing system in Pseudomonas putida strain IsoF

DEFF Research Database (Denmark)

Steidle, A.; Allesen-Holm, M.; Riedel, K.

2002-01-01

Recent reports have shown that several strains of Pseudomonas putida produce N-acylhomoserine lactones (AHLs). These signal molecules enable bacteria to coordinately express certain phenotypic traits in a density-dependent manner in a process referred to as quorum sensing. In this study we have...

INVESTIGATION OF HYPOLIPIDEMIC EFFECT OF SESQUITERPENE Γ-LACTONE AHILLIN IN HEPATOMA TISSUE CULTURE (HTC CELLS

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V. V. Ivanov

2014-01-01

Full Text Available Objective. Investigation of hypolipidemic effect of sesquiterpene γ-lactone ahillin in hepatoma tissue culture (HTC cells.Material and methods. In this study we’ve evaluated the effect of γ-lactone sesquiterpene aсhillin and gemfibrozil (comparator drug on the lipid content in the hepatoma tissue culture (HTC cell which were incubated with a fat emulsion lipofundin by fluorescent method with vital dye Nile Redand staining the cells with the dye Oil Red O. The cell viability was investigated using the MTT-test and staining with Trypan blue.Results. Cultivation cells HTC with aсhillin and gemfibrozilat concentrations ranging from 0.5 to1.5 mM and from0.25 mM to0.5 mM, respectively, resulted in dose-dependent decrease of the fluorescence’s intensity Nile Red. It reflects a decrease in lipid content in the cells. At these concentrations the drugs didn’t have cytotoxic effect and the cell viability didn’t change compared to the control culture.An experimental hyperlipidemia in the hepatoma culture cells was induced by adding to the incubation medium a fat emulsion lipofundin at a final concentration 0.05%. The intensity of fluorescence Nile Red in the cells was increased 4 fold (p < 0.05. This result suggests the significant accumulation of lipids in the cell’s cytosol and confirmed by microscopy after staining neutral lipids with the dye Oil Red O. Under these conditions aсhillin and gemfibrozil reduced lipid content in cells and hadthe effect at concentrations of0.5 mM and0.25 mM respectively.Conclusion. In the lipofundin-mediated model of hyperlipidemia the sesquiterpene lactone aсhillin prevents the lipid accumulation in cells. It confirms by decrease of fluorescence Nile Red and reduction lipid drops which were stained with Oil Red O in cytosol. To establish the molecular targets of aсhillin’saction on lipid metabolism in cell culture HTC we need to investigate a gene expression of key enzymes of lipid metabolism.

Synthesis and optoelectronic properties of a monodispersed macrocycle oligomer consisting of three triarylamine units

Energy Technology Data Exchange (ETDEWEB)

Kong, Qinggang, E-mail: gangq0172@163.com [Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, College of Environmental Science and Engineering, Nanjing University of Information Science and Technology, 219 Ningliu Road, Pukou District, Nanjing 210044 (China); Qian, Haiyan, E-mail: qianhaiy@163.com [College of Material Science and Technology, Nanjing University of Technology, 5 Xinmofan Road, Nanjing 210009 (China); Zhou, Yonghui; Li, Jun; Xiao, Huining [Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, College of Environmental Science and Engineering, Nanjing University of Information Science and Technology, 219 Ningliu Road, Pukou District, Nanjing 210044 (China)

2012-08-15

A monodispersed macrocyclic oligomer constructed by three triarylmine units ((TPAT){sub 3}) was designed and readily synthesized from the monomer of 3-(4 Prime -(phenyl(4 Double-Prime -methylphenyl)amino)-phenyl)pentan-3-ol (TPAT) by means of a simple Friedel-Crafts alkylation reaction. The structure of the resultant macrocycle was examined using FT-IR, NMR and MALDI-TOF mass spectroscopy. Compared with 1,10-bis(di-4-tolylaminophenyl) cyclohexane (TAPC) and tri-p-tolylamine (TTA), (TPAT){sub 3} possesses the three-dimensional chair conformation and the higher T{sub g}. In the photoluminescence (PL) spectrum of (TPAT){sub 3} film, there are no excimer emission peaks in the range of 400-550 nm region as those of TAPC and TTA. Besides an EL peak at 386 nm, the single-layer device occured only the 438 nm excimer emission peak, whose intensity increased with the excitation voltage increase. Using 1,3,5-Tris(N-phenylbenzimidazol-2-yl)-benzene (TPBI) as the electron-transporting layer, the resulting double-layer device ITO/(TPAT){sub 3} (40 nm)/TPBI (40 nm)/Mg:Ag (10:1; 50 nm)/Ag (100 nm) only exhibited a 438 nm maximum symmetrical emission peak under an excitation voltage of 14 V. However, as the applied voltage was increased from 14 V to 19 V, the intensity of the symmetrical curve with a 468 nm peak from exciplex emission gets stronger and stronger. In fact, the resultant emission curve was asymmetrical, due to the overlap of two symmetrical curves with 438 nm and 468 nm peaks, respectively. The maximum luminance and luminous efficiency are 2240 cd m{sup -2} at 18.8 V and 1.73 cd A{sup -1} at 1878 cd m{sup -2} (13.9 V). Highlights: Black-Right-Pointing-Pointer The monodispersed macrocyclic oligomer constructed by three triarylamine units was synthesized and characterized. Black-Right-Pointing-Pointer The PL of (TPAT){sub 3} film does not emerge TAPC and TTA's emission peaks of over 400 nm region. Black-Right-Pointing-Pointer The 438 nm emission peak was found from

Glycosidically bound aroma compounds and impact odorants of four strawberry varieties.

Science.gov (United States)

Ubeda, Cristina; San-Juan, Felipe; Concejero, Belén; Callejón, Raquel M; Troncoso, Ana M; Morales, M Lourdes; Ferreira, Vicente; Hernández-Orte, Purificación

2012-06-20

This paper reports the determination of glycosidically bound aroma compounds and the olfactometric analysis in four strawberry varieties (Fuentepina, Camarosa, Candonga and Sabrina). Different hydrolytic strategies were also studied. The results showed significant differences between acid and enzymatic hydrolysis. In general terms, the greater the duration of acid hydrolysis, the higher was the content of norisoprenoids, volatile phenols, benzenes, lactones, Furaneol, and mesifurane. A total of 51 aglycones were identified, 38 of them unreported in strawberry. Olfactometric analyses revealed that the odorants with higher modified frequencies were Furaneol, γ-decalactone, ethyl butanoate, ethyl hexanoate, ethyl 3-methylbutanoate, diacetyl, hexanoic acid, and (Z)-1,5-octadien-3-one. This last compound, described as geranium/green/pepper/lettuce (linear retention index = 1378), was identified for the first time. Differences with regard to fruity, sweet, floral, and green aroma characters were observed among varieties. In Candonga and Fuentepina, the green character overpowered the sweet. In the other two strawberry varieties sweet attributes were stronger than the rest.

Co-N-macrocyclic modified graphene with excellent electrocatalytic activity for lithium-thionyl chloride batteries

International Nuclear Information System (INIS)

Li, Bimei; Yuan, Zhongzhi; Xu, Ying; Liu, Jincheng

2016-01-01

Highlights: • A Co-N-graphene catalyst composed of CoN 4 -macrocyclic-like (CoN x ) structure is synthesized. • Co-N x -Graphene has effective electrocatalytic activity for Li/SOCl 2 batteries. • The storage stability of the catalyst is attributed to its insolubility in electrolyte. - Abstract: A mixture of cobalt phthalocyanine (CoPc) and graphene is thermally decomposed at 800 °C to synthesize a novel catalyst. Scanning electron microscopy (SEM) and transmission electron microscope (TEM) show that the catalyst retains the lamellar structure of graphene. X-ray diffraction (XRD) reveals that the catalyst is no longer composed of CoPc and high-resolution TEM (HRTEM), X-ray photoelectron spectra (XPS) prove that Co and N elements have entered the graphene molecular structure, thus forming a Co-N x -graphene (Co-N x -G) catalyst composed of a CoN 4 -macrocyclic-like structure. This catalyst serves as an excellent catalyst of thionyl chloride (SOCl 2 ) reduction. Cyclic voltammetry and battery discharge tests reveal that Co-N x -G-800 substantially increases the discharge voltage and capacity of a Li/SOCl 2 battery. Moreover, Co-N x -G-800 exhibits stable catalytic activity during battery storage. Ultraviolet–visible spectroscopy shows that CoPc is soluble in a SOCl 2 electrolyte solution, whereas Co-N x -G-800 is not, this characteristic contributes to the stable catalytic property of Co-N x -G.

Analysis of sesquiterpene lactones, lignans, and flavonoids in wormwood (Artemisia absinthium L.) using high-performance liquid chromatography (HPLC)-mass spectrometry, reversed phase HPLC, and HPLC-solid phase extraction-nuclear magnetic resonance.

Science.gov (United States)

Aberham, Anita; Cicek, Serhat Sezai; Schneider, Peter; Stuppner, Hermann

2010-10-27

Today, the medicinal use of wormwood (Artemisia absinthium) is enjoying a resurgence of popularity. This study presents a specific and validated high-performance liquid chromatography (HPLC)-diode array detection method for the simultaneous determination and quantification of bioactive compounds in wormwood and commercial preparations thereof. Five sesquiterpene lactones, two lignans, and a polymethoxylated flavonoid were baseline separated on RP-18 material, using a solvent gradient consisting of 0.085% (v/v) o-phosphoric acid and acetonitrile. The flow rate was 1.0 mL/min, and chromatograms were recorded at 205 nm. The stability of absinthin was tested exposing samples to light, moisture, and different temperatures. Methanolic and aqueous solutions of absinthin were found to be stable for up to 6 months. This was also the case when the solid compound was kept in the refrigerator at -35 °C. In contrast, the colorless needles, when stored at room temperature, turned yellow. Three degradation compounds (anabsin, anabsinthin, and the new dimer 3'-hydroxyanabsinthin) were identified by HPLC-mass spectrometry and HPLC-solid-phase extraction-nuclear magnetic resonance and quantified by the established HPLC method.

Functional assignment of Glu386 and Arg388 in the active site of l-galactono-¿-lactone dehydrogenase

NARCIS (Netherlands)

Leferink, N.G.H.; Jose, M.D.F.; Berg, van den W.A.M.; Berkel, van W.J.H.

2009-01-01

The flavoenzyme l-galactono-¿-lactone dehydrogenase (GALDH) catalyzes the terminal step of vitamin C biosynthesis in plants. Little is known about the catalytic mechanism of GALDH and related aldonolactone oxidoreductases. Here we identified an essential Glu–Arg pair in the active site of GALDH from

Unsaturated macrocyclic dihydroxamic acid siderophores produced by Shewanella putrefaciens using precursor-directed biosynthesis.

Science.gov (United States)

Soe, Cho Z; Codd, Rachel

2014-04-18

To acquire iron essential for growth, the bacterium Shewanella putrefaciens produces the macrocyclic dihydroxamic acid putrebactin (pbH2; [M + H(+)](+), m/zcalc 373.2) as its native siderophore. The assembly of pbH2 requires endogenous 1,4-diaminobutane (DB), which is produced from the ornithine decarboxylase (ODC)-catalyzed decarboxylation of l-ornithine. In this work, levels of endogenous DB were attenuated in S. putrefaciens cultures by augmenting the medium with the ODC inhibitor 1,4-diamino-2-butanone (DBO). The presence in the medium of DBO together with alternative exogenous non-native diamine substrates, (15)N2-1,4-diaminobutane ((15)N2-DB) or 1,4-diamino-2(E)-butene (E-DBE), resulted in the respective biosynthesis of (15)N-labeled pbH2 ((15)N4-pbH2; [M + H(+)](+), m/zcalc 377.2, m/zobs 377.2) or the unsaturated pbH2 variant, named here: E,E-putrebactene (E,E-pbeH2; [M + H(+)](+), m/zcalc 369.2, m/zobs 369.2). In the latter system, remaining endogenous DB resulted in the parallel biosynthesis of the monounsaturated DB-E-DBE hybrid, E-putrebactene (E-pbxH2; [M + H(+)](+), m/zcalc 371.2, m/zobs 371.2). These are the first identified unsaturated macrocyclic dihydroxamic acid siderophores. LC-MS measurements showed 1:1 complexes formed between Fe(III) and pbH2 ([Fe(pb)](+); [M](+), m/zcalc 426.1, m/zobs 426.2), (15)N4-pbH2 ([Fe((15)N4-pb)](+); [M](+), m/zcalc 430.1, m/zobs 430.1), E,E-pbeH2 ([Fe(E,E-pbe)](+); [M](+), m/zcalc 422.1, m/zobs 422.0), or E-pbxH2 ([Fe(E-pbx)](+); [M](+), m/zcalc 424.1, m/zobs 424.2). The order of the gain in siderophore-mediated Fe(III) solubility, as defined by the difference in retention time between the free ligand and the Fe(III)-loaded complex, was pbH2 (ΔtR = 8.77 min) > E-pbxH2 (ΔtR = 6.95 min) > E,E-pbeH2 (ΔtR = 6.16 min), which suggests one possible reason why nature has selected for saturated rather than unsaturated siderophores as Fe(III) solubilization agents. The potential to conduct multiple types of ex situ chemical

Hydrodeoxygenation of the angelica lactone dimer, a cellulose-based feedstock: simple, high-yield synthesis of branched C7 -C10 gasoline-like hydrocarbons.

Science.gov (United States)

Mascal, Mark; Dutta, Saikat; Gandarias, Inaki

2014-02-10

Dehydration of biomass-derived levulinic acid under solid acid catalysis and treatment of the resulting angelica lactone with catalytic K2 CO3 produces the angelica lactone dimer in excellent yield. This dimer serves as a novel feedstock for hydrodeoxygenation, which proceeds under relatively mild conditions with a combination of oxophilic metal and noble metal catalysts to yield branched C7 -C10 hydrocarbons in the gasoline volatility range. Considering that levulinic acid is available in >80 % conversion from raw biomass, a field-to-tank yield of drop-in, cellulosic gasoline of >60 % is possible. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study

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Jesus Vicente De Julián-Ortiz

2016-07-01

Full Text Available Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cations. In this study, the relative stabilities of these conformations were predicted computationally by semi-empirical and density functional theory approximations, and the reorganization from closed to open conformations was simulated by using the Monte Carlo multiple minimum method.

Synthesis and study of rare earth ortho-hydroxyphenyliminodiacetates with open lactone ring

International Nuclear Information System (INIS)

Martynenko, L.I.; Mitrofanova, N.D.; Muratova, N.M.; Kurbatova, S.V.

1978-01-01

New La, Pr, Nd, Sm, Dy, Er, and Y o-oxyphenyliminodiacetates of Ln 2 (HL) 3 xnH 2 O composition have been synthesized using the reaction of Ln chloride solutions with o-oxyphenyliminodiacetic acid previously converted into a soluble K 2 HL salt. According to the data of infrared spectra, the ligand contains an open lactone ring and ionized carboxylic groups. At the temperature of 80-190 deg the complexes undergo dehydration. The order of dehydration reaction for La, Nd, and Y complexes is equal to 2, activation energies are equal to 16.9, 12.5 and 13.2 kcal/mol, respectively

Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis

DEFF Research Database (Denmark)

Geisenberger, O; Givskov, M; Riedel, K

2000-01-01

The N-acyl-L-homoserine lactones (AHLs) produced by sequential Pseudomonas aeruginosa isolates from chronically infected patients with cystic fibrosis were analyzed by thin-layer chromatography. It is demonstrated that both the amounts and the types of molecules synthesized by isolates from...

PA0305 of Pseudomonas aeruginosa is a quorum quenching acylhomoserine lactone acylase belonging to the Ntn hydrolase superfamily

NARCIS (Netherlands)

Wahjudi, Mariana; Papaioannou, Evelina; Hendrawati, Oktavia; van Assen, Aart H. G.; van Merkerk, Ronald; Cool, Robbert H.; Poelarends, Gerrit J.; Quax, Wim

The Pseudomonas aeruginosa PAO1 genome has at least two genes, pvdQ and quiP, encoding acylhomoserine lactone (AHL) acylases. Two additional genes, pa 1893 and pa0305, have been predicted to encode penicillin acylase proteins, but have not been characterized. Initial studies on a pa0305 transposon

Macrocyclic receptors immobilized to monodisperse porous polymer particles by chemical grafting and physical impregnation for strontium capture: A comparative study

Energy Technology Data Exchange (ETDEWEB)

Song, Yang [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing (China); Du, Yi [Department of Chemical Engineering, Laboratory for Advanced Materials, Tsinghua University, Beijing (China); Lv, Dachao [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing (China); Ye, Gang, E-mail: yegang@tsinghua.edu.cn [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing (China); Wang, Jianchen [Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing (China)

2014-06-01

Graphical abstract: Macrocyclic receptors grafted to monodisperse porous polymer particles for Sr(II) capture. - Highlights: • Synthesis of novel selective Sr adsorbent grafted with macrocyclic receptors. • New monodisperse porous polymer particles used to promote Sr adsorption. • Comparative study and discussion on adsorption behaviour and mechanism. • A chromatographic process proposed for Sr separation in simulated HLLW. - Abstract: Separation of strontium is of great significance for radioactive waste treatment and environmental remediation after nuclear accidents. In this work, a novel class of adsorbent (Crown-g-MPPPs) was synthesized by chemical grafting a macrocyclic ether receptor to monodisperse porous polymer particles (MPPPs) for strontium adsorption. Meanwhile, a counterpart material (Crown@MPPPs) with the receptor molecules immobilized to the MPPPs substrate by physical impregnation was prepared. To investigate how the immobilization manner and distribution of the receptors influence the adsorption ability, a comparative study on the adsorption behaviour of the two materials towards Sr(II) in HNO{sub 3} media was accomplished. Due to the shorter diffusion path and covalently-bonded structure, Crown-g-MPPPs showed faster adsorption kinetics and better stability for cycle use. While Crown@MPPPs had the advantages of facile synthesis and higher adsorption capacity, owing to the absence of conformational constraint to form complexation with Sr(II). Kinetic functions (Lagergren pseudo-first-order/pseudo-second-order functions) and adsorption isotherm models (Langmuir/Freundlich models) were used to fit the experimental data and examine the adsorption mechanism. On this basis, a chromatographic process was proposed by using Crown@MPPPs for an effective separation of Sr(II) (91%) in simulated high level liquid waste (HLLW)

Simultaneous quantitative determination of 11 sesquiterpene lactones in Jerusalem artichoke (Helianthus tuberosus L.) leaves by ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Science.gov (United States)

Yuan, Xiaoyan; Yang, Qianxu

2017-04-01

A method of ultra high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was developed for the simultaneous quantification of 11 sesquiterpene lactones in 11 Jerusalem artichoke leaf samples harvested in a number of areas at different periods. The optimal chromatographic conditions were achieved on a ZORBAX Eclipse Plus C 18 column (3.0 × 150 mm, 1.8 μm) with linear gradient elution of methanol and water in 8 min. Quantitative analysis was carried out under selective ion monitoring mode. All of the sesquiterpene lactones showed good linearity (R 2 ≥ 0.9949), repeatability (relative standard deviations Jerusalem artichoke leaf samples from different areas. Among them, the content of sesquiterpene lactones in the sample collected from Dalian, Liaoning province was the highest and the early flowering period was considered to be the optimal harvest time. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phytotoxic properties of cnicin, a sesquiterpene lactone fromcentaurea maculosa (spotted knapweed).

Science.gov (United States)

Kelsey, R G; Locken, L J

1987-01-01

Water and solvent extracts from the aerial tissues ofCentaurea maculosa, spotted knapweed, inhibited the root growth of lettuce. Column chromatography and lettuce bioassay of a chloroform extract led to the isolation of cnicin, a sesquiterpene lactone. Pure cnicin was bioassayed at 0, 1, 2, 4, 6, 8, and 10 mg/5 ml water with lettuce, created wheatgrass, bluebunch wheatgrass, rough fescue, western larch, lodgepole pine, and spotted knapweed. Germination was inhibited at one or more concentrations for all species except lodgepole pine and spotted knapweed. Growth, particularly of the roots, was retarded between 1 and 4 mg of cnicin. Lettuce, bluebunch wheatgrass, and spotted knapweed were inhibited significantly at all concentrations tested.

Biomechanical Assessment of the Strength of Volleyball Players in Different Stages of the Training Macrocycle

Directory of Open Access Journals (Sweden)

Śliwa Marcin

2015-09-01

Full Text Available Introduction. In order to help volleyball players achieve superior results, their coaches are constantly seeking new training methods. One of the methods used to improve the effectiveness of the training that is being implemented is conducting tests which make it possible to assess the player’s locomotor system in terms of its motor and biomechanical functions. The aim of the study was to determine the torque of the knee flexor and extensor muscles of volleyball players in three stages of the annual macrocycle.

Detection of the quorum sensing signal molecule N-Dodecanoyl-DL-homoserine lactone below 1 nanomolarconcentrations using surface enhanced Raman spectroscopy

DEFF Research Database (Denmark)

Claussen, Anetta; Abdali, Salim; Berg, Rolf W.

2013-01-01

suitable tool for in situ measurements of low Acyl-Homoserine Lactone (AHL) concentrations in biofilms containing QS bacteria. Signal molecules communicate information about their environment and coordinate certain physiological activities in QS systems that exist in many bacteria. SERS enables detection...

The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations

DEFF Research Database (Denmark)

Thastrup, Ole; Linnebjerg, H; Bjerrum, P J

1987-01-01

We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release...

CYTOTOXICITY OF FLAVONOIDS AND SESQUITERPENE LACTONES FROM ARNICA SPECIES AGAINST THE GLC(4) AND THE COLO-320 CELL-LINES

NARCIS (Netherlands)

WOERDENBAG, HJ; MERFORT, [No Value; PASSREITER, CM; SCHMIDT, TJ; WILLUHN, G; VANUDEN, W; PRAS, N; KAMPINGA, HH; KONINGS, AWT

1994-01-01

The cytotoxicity of 21 flavonoids and 5 sesquiterpene lactones, as present in Arnica species, was studied in GLC(4), a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. Following continuous incubation,

Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic

DEFF Research Database (Denmark)

Persson, T.; Rasmussen, Thomas Bovbjerg; Skindersoe, M.

2005-01-01

within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-L-homoserine lactone (10c) was identified. Together with data collected for the other...

Heterocycles by Transition Metals Catalyzed Intramolecular Cyclization of Acetylene Compounds

International Nuclear Information System (INIS)

Vizer, S.A.; Yerzhanov, K.B.; Dedeshko, E.C.

2003-01-01

Review shows the new strategies in the synthesis of heterocycles, having nitrogen, oxygen and sulfur atoms, via transition metals catalyzed intramolecular cyclization of acetylenic compounds on the data published at the last 30 years, Unsaturated heterocyclic compounds (pyrroles and pyrroline, furans, dihydro furans and benzofurans, indoles and iso-indoles, isoquinolines and isoquinolinones, aurones, iso coumarins and oxazolinone, lactams and lactones with various substitutes in heterocycles) are formed by transition metals, those salts [PdCl 2 , Pd(OAc) 2 , HgCl 2 , Hg(OAc) 2 , Hg(OCOCF 3 ) 2 , AuCl 3 ·2H 2 O, NaAuCl 4 ·2H 2 O, CuI, CuCl], oxides (HgO) and complexes [Pd(OAc) 2 (PPh 3 )2, Pd(PPh 3 ) 4 , PdCl 2 (MeCN) 2 , Pd(OAc ) 2 /TPPTS] catalyzed intramolecular cyclization of acetylenic amines, amides, ethers, alcohols, acids, ketones and βdiketones. More complex hetero polycyclic systems typical for natural alkaloids can to obtain similar. Proposed mechanisms of pyrroles, isoquinolines, iso indoles and indoles, benzofurans and iso coumarins, thiazolopyrimidinones formation are considered. (author)

Volatile flavor compounds, total polyphenolic contents and antioxidant activities of a China gingko wine.

Science.gov (United States)

Wang, Xu; Xie, Kelin; Zhuang, Haining; Ye, Ran; Fang, Zhongxiang; Feng, Tao

2015-09-01

The volatile compounds in gingko wine, a novel functional wine, were extracted by head-space solid phase micro-extraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS) coupled with odor activity value (OAV) and relative odor contribution (ROC) analyses. In addition, the total polyphenolic content of gingko wine was determined using the Folin-Ciocalteu reagent, and its antioxidant capacity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Fifty-eight compounds were tentatively identified, including 13 esters, 10 alcohols, 11 acids, 12 carbonyl compounds, 2 lactones, 2 phenols, and 8 hydrocarbons. Ethyl hexanoate, ethyl pentanoate, nonanal, ethyl butyrate and ethyl heptanoate were the major contributors to the gingko wine aroma based on the results of OAV and ROC. The total phenols content of the gingko wine was 456 mg/L gallic acid equivalents, and its antioxidant capacity was higher than those of typical Chinese liquors analyzed in this paper. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fungal strains as catalysts for the biotransformation of halolactones by hydrolytic dehalogenation with the dimethylcyclohexane system.

Science.gov (United States)

Grabarczyk, Małgorzata

2012-08-14

Bicyclic chloro-, bromo- and iodo-γ-lactones with dimethylcyclohexane rings were used as substrates for bioconversion by several fungal strains (Fusarium, Botrytis and Beauveria). Most of the selected microorganisms transformed these lactones by hydrolytic dehalogenation into the new compound cis-2-hydroxy-4,6-dimethyl-9-oxabicyclo[4.3.0]- nonan-8-one, mainly the (-)-isomer. When iodo-γ-lactone was used as the substrate, two products were observed: a hydroxy-γ-lactone and an unsaturated lactone. The structures of all substrates and products were established on the basis of their spectral data. The mechanism of dehalogenation of three halolactones was also studied.

Resolution of canine ocular thelaziosis in avermectin-sensitive Border Collies from Spain.

Science.gov (United States)

Calero-Bernal, Rafael; Sánchez-Murillo, José Marín; Alarcón-Elbal, Pedro María; Sánchez-Moro, José; Latrofa, Maria Stefanía; Dantas-Torres, Filipe; Otranto, Domenico

2014-02-24

Ocular thelaziosis by Thelazia callipaeda is an emerging disease that affects primarily dogs, but also cats, foxes and other wild carnivores, as well as humans. Three clinical cases of unilateral conjunctivitis caused by Thelazia nematodes were detected in Border Collie, a dog breed intolerant to the macrocyclic lactones. Animals came from southwestern Spain, on the border with Portugal. Eight worms were collected and identified molecularly as T. callipaeda by amplification and sequencing of partial cytochrome c oxidase subunit 1 gene. Oral treatment with mebendazole 20mg/kg (Telmin(®)) was effective in curing the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

New lanthanide(III) complexes of chiral nonadendate macrocyclic amine derived from (1R,2R)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol

Energy Technology Data Exchange (ETDEWEB)

Paluch, Marta [Department of Chemistry, University of Wroclaw, 14 F. Joliot-Curie, 50-383 Wroclaw (Poland); Lisowski, Jerzy [Department of Chemistry, University of Wroclaw, 14 F. Joliot-Curie, 50-383 Wroclaw (Poland)], E-mail: jurekl@wchuwr.chem.uni.wroc.pl

2008-02-28

The series of complexes [LnH{sub 4}L(NO{sub 3}){sub 2}](NO{sub 3}){sub 2}.nH{sub 2}O (Ln = La, Ce, Pr, Nd, Gd, Tb, Ho, Er, Tm) of the positively charged protonated form of a chiral macrocyclic amine H{sub 4}L{sup +}, derived from the 3 + 3 condensation product of (1R,2R)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol, have been synthesized. The series of complexes Na{sub x}[LnL](X){sub y}(OH){sub x-y}.n(solv) (X = NO{sup 3-} or Cl{sup -}, and Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) of the deprotonated anionic form of the ligand, L{sup 3-}, have also been synthesised. The complexes have been characterised by elemental analyses, {sup 1}H NMR and ESI MS spectra. The X-ray crystal structures of the [LaH{sub 4}L(NO{sub 3}){sub 2}](NO{sub 3}){sub 2}.5CH{sub 3}OH and [GdH{sub 4}L(NO{sub 3}){sub 2}](NO{sub 3}){sub 2}.5CH{sub 3}OH complexes have been determined. The two complexes are isostructural, and the protonated macrocycle acts as pentadentate ligand. The Ln(III) ion is bound to three phenolate oxygen atoms and two amine nitrogen atoms of the macrocyclic ligand and its coordination sphere is completed by the two axial bidendate nitrate anions.

Visible-Light-Promoted Metal-Free Aerobic Oxidation of Primary Amines to Acids and Lactones.

Science.gov (United States)

Cheng, Xiaokai; Yang, Bo; Hu, Xingen; Xu, Qing; Lu, Zhan

2016-12-05

A unique metal-free aerobic oxidation of primary amines via visible light photocatalytic double carbon-carbon bonds cleavage and multi carbon-hydrogen bonds oxidation was observed. Aerobic oxidation of primary amines could be controlled to afford acids by using dioxane with 18 W CFL, and lactones by using DMF with 8 W green LEDs, respectively. A plausible mechanism was proposed based on control experiments. This observation showed direct evidences for the fragmentation in the aerobic oxidation of aliphatic primary amines. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authentication of pineapple (Ananas comosus [L.] Merr.) fruit maturity stages by quantitative analysis of γ- and δ-lactones using headspace solid-phase microextraction and chirospecific gas chromatography-selected ion monitoring mass spectrometry (HS-SPME-GC-SIM-MS).

Science.gov (United States)

Steingass, Christof B; Langen, Johannes; Carle, Reinhold; Schmarr, Hans-Georg

2015-02-01

Headspace solid phase microextraction and chirospecific gas chromatography-mass spectrometry in selected ion monitoring mode (HS-SPME-GC-SIM-MS) allowed quantitative determination of δ-lactones (δ-C8, δ-C10) and γ-lactones (γ-C6, γ-C8, γ-C10). A stable isotope dilution assay (SIDA) with d7-γ-decalactone as internal standard was used for quantitative analysis of pineapple lactones that was performed at three progressing post-harvest stages of fully ripe air-freighted and green-ripe sea-freighted fruits, covering the relevant shelf-life of the fruits. Fresh pineapples harvested at full maturity were characterised by γ-C6 of high enantiomeric purity remaining stable during the whole post-harvest period. In contrast, the enantiomeric purity of γ-C6 significantly decreased during post-harvest storage of sea-freighted pineapples. The biogenetical background and the potential of chirospecific analysis of lactones for authentication and quality evaluation of fresh pineapple fruits are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Compounds from multilayer plastic bags cause reproductive failures in artificial insemination.

Science.gov (United States)

Nerin, C; Ubeda, J L; Alfaro, P; Dahmani, Y; Aznar, M; Canellas, E; Ausejo, R

2014-05-09

High levels of reproductive failure were detected in some Spanish sow farms in the Spring of 2010. Regular returns to estrus and variable reductions in litter size were observed. The problem started suddenly and did not appear to be related to the quality of the ejaculates, disease, alterations of body condition or any other apparent reasons. Subsequent studies determined that the problem was the origin of the plastic bags used for semen storage. Chemical analysis of the suspicious bags identified unexpected compounds such as BADGE, a cyclic lactone and an unknown phthalate that leached into the semen at concentrations of 0.2 to 2.5 mg/L. Spermatozoa preserved in these bags passed all of the routine quality control tests, and no differences were observed between storage in the control and suspicious bags (p > 0.05). In vitro fecundation tests and endocrine profiler panel analysis (EPP) did not show any alterations, whereas the in vivo tests confirmed the described failure. This is the first described relationship between reproductive failure and toxic compounds released from plastic bags.

Compounds from multilayer plastic bags cause reproductive failures in artificial insemination

Science.gov (United States)

Nerin, C.; Ubeda, J. L.; Alfaro, P.; Dahmani, Y.; Aznar, M.; Canellas, E.; Ausejo, R.

2014-05-01

High levels of reproductive failure were detected in some Spanish sow farms in the Spring of 2010. Regular returns to estrus and variable reductions in litter size were observed. The problem started suddenly and did not appear to be related to the quality of the ejaculates, disease, alterations of body condition or any other apparent reasons. Subsequent studies determined that the problem was the origin of the plastic bags used for semen storage. Chemical analysis of the suspicious bags identified unexpected compounds such as BADGE, a cyclic lactone and an unknown phthalate that leached into the semen at concentrations of 0.2 to 2.5 mg/L. Spermatozoa preserved in these bags passed all of the routine quality control tests, and no differences were observed between storage in the control and suspicious bags (p > 0.05). In vitro fecundation tests and endocrine profiler panel analysis (EPP) did not show any alterations, whereas the in vivo tests confirmed the described failure. This is the first described relationship between reproductive failure and toxic compounds released from plastic bags.

Neighbor-Directed Histidine N (s)–Alkylation: A Route to Imidazolium-Containing Phosphopeptide Macrocycles-Biopolymers | Center for Cancer Research

Science.gov (United States)

Our recently discovered, selective, on-resin route to N(s)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently serve to charge-mask the phosphoamino acid group that directed their formation.

Dissociation kinetics of acyclic and macrocyclic polyaminopolycarboxylate complexes of yttrium

International Nuclear Information System (INIS)

Pathak, P.N.; Manchanda, V.K.

2000-01-01

Dissociation kinetics of Y III complexes of a linear as well as two macrocyclic polyaminopolycarboxylates, ethylenediamine diacetic acid (EDDA), 1,7-diaza-4,10,13-trioxacyclopentadecane-N,N'-diacetic acid (K21DA) and 1,10-diaza-4,7,13,16-tetraoxacyclooctadecane-N,N'-diacetic acid (K22DA) have been studied at a constant ionic strength (0.1 M) under varying (H + ) and temperatures. Cu II ion acts as the scavenger of the free ligand. Dissociation rate of Y III -K21DA is insensitive to Cu II and acetate (used as buffer anion) concentrations. Kinetic stability of the three complexes follow the order : Y III -K22DA>Y III -K21DA>Y III -EDDA. Enthalpies of activation for K21DA and K22DA complexes of Y III are also evaluated. Thermodynamic stability constant (log K) for Y III -K22DA complex is 10.81 ± 0.04. (author)

Clinical, biological, and skin histopathologic effects of ionic macrocyclic and nonionic linear gadolinium chelates in a rat model of nephrogenic systemic fibrosis.

Science.gov (United States)

Fretellier, Nathalie; Idée, Jean-Marc; Guerret, Sylviane; Hollenbeck, Claire; Hartmann, Daniel; González, Walter; Robic, Caroline; Port, Marc; Corot, Claire

2011-02-01

the purpose of this study was to compare the clinical, pathologic, and biochemical effects of repeated administrations of ionic macrocyclic or nonionic linear gadolinium chelates (GC) in rats with impaired renal function. rats submitted to subtotal nephrectomy were allocated to single injections of 2.5 mmol/kg of gadodiamide (nonionic linear chelate), nonformulated gadodiamide (ie, without the free ligand caldiamide), gadoterate (ionic macrocyclic chelate), or saline for 5 consecutive days. Blinded semi-quantitative histopathologic and immunohistochemical examinations of the skin were performed, as well as clinical, hematological, and biochemical follow-up. Rats were killed at day 11. Long-term (up to day 32) follow-up of rats was also performed in an auxiliary study. epidermal lesions (ulcerations and scabs) were found in 4 of the 10 rats treated with nonformulated gadodiamide. Two rats survived the study period. Inflammatory signs were observed in this group. No clinical, hematological, or biochemical signs were observed in the saline and gadoterate- or gadodiamide-treated groups. Plasma fibroblast growth factor-23 levels were significantly higher in the gadodiamide group than in the gadoterate group (day 11). Decreased plasma transferrin-bound iron levels were measured in the nonformulated gadodiamide group. Histologic lesions were in the range: nonformulated gadodiamide (superficial epidermal lesions, inflammation, necrosis, and increased cellularity in papillary dermis) > gadodiamide (small superficial epidermal lesions and signs of degradation of collagen fibers in the dermis) > gadoterate (very few pathologic lesions, similar to control rats). repeated administration of the nonionic linear GC gadodiamide to renally impaired rats is associated with more severe histologic lesions and higher FGF-23 plasma levels than the macrocyclic GC gadoterate.

Targeting N-acyl-homoserine-lactones to mitigate membrane biofouling based on quorum sensing using a biofouling reducer.

Science.gov (United States)

Siddiqui, Muhammad Faisal; Sakinah, Mimi; Singh, Lakhveer; Zularisam, A W

2012-10-31

Exploring novel biological anti-quorum sensing (QS) agents to control membrane biofouling is of great worth in order to allow sustainable performance of membrane bioreactors (MBRs) for wastewater treatment. In recent studies, QS inhibitors have provided evidence of alternative route to control membrane biofouling. This study investigated the role of Piper betle extract (PBE) as an anti-QS agent to mitigate membrane biofouling. Results demonstrated the occurrence of the N-acyl-homoserine-lactone (AHL) autoinducers (AIs), correlate QS activity and membrane biofouling mitigation. The AIs production in bioreactor was confirmed using an indicator strain Agrobacterium tumefaciens (NTL4) harboring plasmid pZLR4. Moreover, three different AHLs were found in biocake using thin layer chromatographic analysis. An increase in extracellular polymeric substances (EPS) and transmembrane pressure (TMP) was observed with AHL activity of the biocake during continuous MBR operation, which shows that membrane biofouling was in close relationship with QS activity. PBE was verified to mitigate membrane biofouling via inhibiting AIs production. SEM analysis further confirmed the effect of PBE on EPS and biofilm formation. These results exhibited that PBE could be a novel agent to target AIs for mitigation of membrane biofouling. Further work can be carried out to purify the active compound of Piper betle extract to target the QS to mitigate membrane biofouling. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis and phytotoxicity of 4,5 functionalized tetrahydrofuran-2-ones

Energy Technology Data Exchange (ETDEWEB)

Resende, Gabriela C.; Alvarenga, Elson S., E-mail: elson@ufv.br [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica; Galindo, Juan C.G.; Macias, Francisco A. [Grupo de Alelopatia, Departamento de Quimica Organica, Facultad de Ciencias, Universidad de Cadiz (Spain)

2012-12-15

In this work we report a versatile synthesis of fourteen {gamma}-lactones all structurally related, nine of which are novel compounds, accomplished from the readily available furfural. The phytotoxic activity of the synthesized compounds was evaluated in vitro by the influence on the growth of heat coleoptiles. The percentages of inhibition were mostly small and not statistically different from control after the third dilution (100 Greek-Small-Letter-Mu mol L{sup -1}). In general, {alpha},{beta}-unsaturated lactones presented better activities than the saturated ones. The most active compounds presented 51, 68 and 76% of inhibition in 1000 Greek-Small-Letter-Mu mol L-1. The results indicate that regardless of saturation, the presence of the {gamma}-lactone moiety is important for the bioactivity, but their presence has no implications with potency. (author)

Terpenoid Composition and Base Sequences of Ligularia virgaurea (Asteraceae) Grown in the Hengduan Mountain Area in China and a Comment on Drawing Structures.

Science.gov (United States)

Tori, Motoo

2016-01-01

A chemical analysis of 30 samples of Ligularia virgaurea (Asteraceae) collected in Sichuan province and its adjacent territories in China was reviewed. These samples afforded 146 compounds, 73 of which were novel, and the chemical constituents were classified into 8 categories: (1) simple eremophilanes (without ring C) and eudesmanes including nor-derivatives, (2) furanoeremophilanes and lactones with a 1(10)-saturated bond, (3) furanoeremophilanes and lactones with a 1(10)-unsaturated bond, 1,10-epoxide, or 10-ol, (4) furanoeremophilanes and lactones with 1(10)-en-2-one, 1(10)-en-2-ol, or 1-en-3-one, (5) furanoeremophilanes and lactones with 1(10)-en-9-one, 1(10)-en-9-ol, or 1,10-epoxy-9-one, (6) cacalol and their derivatives, (7) bakkanes and their derivatives, and (8) others, as shown in Tables 1-7. In these studies, five chemotypes were identified in addition to three clades from the DNA sequences of L. virgaurea. The structural determination of some compounds was also discussed and a comment on how to express the real structure was proposed, particularly for spiro compounds.

Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid.

Science.gov (United States)

Meckel, M; Bergmann, R; Miederer, M; Roesch, F

2017-01-01

Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68 Ga-labelled analogues, endoradiotheraphy with 177 Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA PAM and DOTA ZOL (MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68 Ga and the β - emitting nuclide 177 Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [ 18 F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68 Ga and >98 % with 177 Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [ 68 Ga]DOTA ZOL (SUV Femur  = 5.4 ± 0.6) followed by [ 18 F]NaF (SUV Femur  = 4.8 ± 0.2), [ 68 Ga]DOTA PAM (SUV Femur  = 4.5 ± 0.2) and [ 68 Ga]BPAPD (SUV Femur  = 3.2 ± 0.3). [ 177 Lu]DOTA ZOL showed a similar distribution as the diagnostic 68 Ga complex. The 68 Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [ 68 Ga]DOTA ZOL , which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177 Lu. The therapeutic compound [ 177 Lu]DOTA ZOL showed a high target-to-background ratio. SPECT experiments showed concordance

A New Method for the Synthesis of 2,3-Aziridino-2,3-dideoxyhexonamides and Their Conversion into 3-Amoni-2,3-dideoxyhexonic Acids

DEFF Research Database (Denmark)

Jørgensen, Christel Thea; Pedersen, Christian; Søtofte, Inger

1998-01-01

The new 2,3-Aziridino-2,3-dideoxyhexonamides 3 and 11 were prepared by a three-step procedure from commercially available D-glucono-1,5-lactone and D-gulono-1,4-lactone, respectively. The lactones were converted into methyl 3,4;5,6-di-O-isopropylidene-2-Omesyl esters 2 and 10, which upon treatmen...... with ammonia formed the title aziridino compounds. These were reductively cleaved by hydrazine to give 3-amino-2,3-dideoxyhexonic hydrazides 13 and 15, which were easily converted into corresponding lactone 14 and acid 16, respectively....

Complexes of DOTA-bisphosphonate conjugates: probes for determination of adsorption capacity and affinity constants of hydroxyapatite.

Science.gov (United States)

Vitha, Tomas; Kubícek, Vojtech; Hermann, Petr; Kolar, Zvonimir I; Wolterbeek, Hubert Th; Peters, Joop A; Lukes, Ivan

2008-03-04

The adsorption on hydroxyapatite of three conjugates of a bisphosphonate and a macrocycle having C1, C2, and C3 spacers and their terbium complexes was studied by the radiotracer method using 160Tb as the label. The radiotracer-containing complex of the conjugate with the C3 spacer was used as a probe for the determination of the adsorption parameters of other bisphosphonates that lack a DOTA unit. A physicochemical model describing the competitive adsorption was successfully applied in the fitting of the obtained data. The maximum adsorption capacity of bisphosphonates containing bulky substituents is determined mainly by their size. For bisphosphonates having no DOTA moiety, the maximum adsorption capacity is determined by the electrostatic repulsion between negatively charged bisphosphonate groups. Compounds with a hydroxy or amino group attached to the alpha-carbon atom show higher affinities. Macrocyclic compounds containing a short spacer between the different bisphosphonic acid groups and the macrocyclic unit exhibit high affinities, indicating a synergic effect of the bisphosphonic and the macrocyclic groups during adsorption. The competition method described uses a well-characterized complex and allows a simple evaluation of the adsorption behavior of bisphosphonates. The application of the macrocycle-bisphosphonate conjugates allows easy radiolabeling via complexation of a suitable metal isotope.

Reductive decarboxylation of bicyclic prolinic systems: a new approach to the enantioselective synthesis of the Geissman-Waiss lactone. X-ray structure determination of a key lactone intermediate

Directory of Open Access Journals (Sweden)

Ambrósio João Carlos L.

2003-01-01

Full Text Available Two concise and enantioselective syntheses of the necine base precursors (1R,5R-N-Cbz and N-Boc-2-oxa-6-azabicyclo[3.3.0]octan-3-ones (Geissman-Waiss lactones were carried out from two enantiomerically pure endocyclic five-membered enecarbamates with overall yields of 23% and 26%, respectively. The synthetic strategy made use of a highly effective and stereoselective [2+2]cycloaddition of enantiomerically pure endocyclic enecarbamates with dichloroketene, as well as an efficient decarboxylation step of a bicyclic alpha-amino acid employing Boger's acyl selenide protocol employing tributyltin hydride. Interesting aspects concerning the regiochemical outcome of Baeyer-Villiger oxidations of bicyclic cyclobutanones are also reported, in which the usual stereoelectronic bias of Baeyer-Villiger oxidation seems to be counterbalanced by steric effects on the putative Criegee intermediate.

Hydrophobic, Hydrophilic, and Amphiphilic Polyglycocarbonates with Linear and Macrocyclic Architectures from Bicyclic Glycocarbonates Derived from CO2 and Glucoside

KAUST Repository

Pati, Debasis; Feng, Xiaoshuang; Hadjichristidis, Nikolaos; Gnanou, Yves

2017-01-01

Two bicyclic glycocarbonates were synthesized in five steps from α-methyl-d-glucoside without resorting to phosgene or to its derivatives for the first time. The 4- and 6-positions of glucose were modified to introduce a six-membered carbonate ring, using CO as the carbonylating reagent; the 2- and 3-positions of the same glucoside substrate were first transformed into either methyl or triethylene glycol monomethyl ether groups to protect these positions from undesirable reactions and also to impart hydrophobicity in the first case and hydrophilicity in the second. The polymerization behavior of these bicyclic glycocarbonates was then investigated under different conditions. On the one hand, through ring-opening polymerization of the above monomers, linear polyglycocarbonate homopolymers and diblock copolymers were obtained initiated by p-methylbenzyl alcohol using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst; on the other hand, macrocyclic polyglycocarbonate homopolymers and diblock copolymers were grown using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) which served as zwitterionic initiator. The various architectures derived were all thoroughly characterized by NMR, GPC, and MALDI-tof and shown to exhibit the expected structure. Finally, the self-assembly of linear and macrocyclic amphiphilic copolyglycocarbonates in water was investigated and characterized by cryo-TEM.

Hydrophobic, Hydrophilic, and Amphiphilic Polyglycocarbonates with Linear and Macrocyclic Architectures from Bicyclic Glycocarbonates Derived from CO2 and Glucoside

KAUST Repository

Pati, Debasis

2017-02-09

Two bicyclic glycocarbonates were synthesized in five steps from α-methyl-d-glucoside without resorting to phosgene or to its derivatives for the first time. The 4- and 6-positions of glucose were modified to introduce a six-membered carbonate ring, using CO as the carbonylating reagent; the 2- and 3-positions of the same glucoside substrate were first transformed into either methyl or triethylene glycol monomethyl ether groups to protect these positions from undesirable reactions and also to impart hydrophobicity in the first case and hydrophilicity in the second. The polymerization behavior of these bicyclic glycocarbonates was then investigated under different conditions. On the one hand, through ring-opening polymerization of the above monomers, linear polyglycocarbonate homopolymers and diblock copolymers were obtained initiated by p-methylbenzyl alcohol using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst; on the other hand, macrocyclic polyglycocarbonate homopolymers and diblock copolymers were grown using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) which served as zwitterionic initiator. The various architectures derived were all thoroughly characterized by NMR, GPC, and MALDI-tof and shown to exhibit the expected structure. Finally, the self-assembly of linear and macrocyclic amphiphilic copolyglycocarbonates in water was investigated and characterized by cryo-TEM.

Taraxinic acid, a hydrolysate of sesquiterpene lactone glycoside from the Taraxacum coreanum NAKAI, induces the differentiation of human acute promyelocytic leukemia HL-60 cells.

Science.gov (United States)

Choi, Jung-Hye; Shin, Kyung-Min; Kim, Na-Young; Hong, Jung-Pyo; Lee, Yong Sup; Kim, Hyoung Ja; Park, Hee-Juhn; Lee, Kyung-Tae

2002-11-01

The present work was performed to elucidate the active moiety of a sesquiterpene lactone, taraxinic acid-1'-O-beta-D-glucopyranoside (1). from Taraxacum coreanum NAKAI on the cytotoxicity of various cancer cells. Based on enzymatic hydrolysis and MTT assay, the active moiety should be attributed to the aglycone taraxinic acid (1a). rather than the glycoside (1). Taraxinic acid exhibited potent antiproliferative activity against human leukemia-derived HL-60. In addition, this compound was found to be a potent inducer of HL-60 cell differentiation as assessed by a nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD 14 and CD 66 b surface antigens. These results suggest that taraxinic acid induces the differentiation of human leukemia cells to monocyte/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during taraxinic acid-dependent HL-60 cell differentiation, whereas p21(CIP1) and p27(KIP1) were up-regulated. Taken together, our results suggest that taraxinic acid may have potential as a therapeutic agent in human leukemia.

Isolation of Bioactive Compounds from Sunflower Leaves (Helianthus annuus L.) Extracted with Supercritical Carbon Dioxide.

Science.gov (United States)

El Marsni, Zouhir; Torres, Ascension; Varela, Rosa M; Molinillo, José M G; Casas, Lourdes; Mantell, Casimiro; Martinez de la Ossa, Enrique J; Macias, Francisco A

2015-07-22

The work described herein is a continuation of our initial studies on the supercritical fluid extraction (SFE) with CO2 of bioactive substances from Helianthus annuus L. var. Arianna. The selected SFE extract showed high activity in the wheat coleoptile bioassay, in Petri dish phytotoxicity bioassays, and in the hydroponic culture of tomato seeds. Chromatographic fractionations of the extracts and a spectroscopic analysis of the isolated compounds showed 52 substances belonging to 10 different chemical classes, which were mainly sesquiterpene lactones, diterpenes, and flavonoids. Heliannuol M (31), helivypolides K and L (36, 37), and helieudesmanolide B (38) are described for the first time in the literature. Metabolites have been tested in the etiolated wheat coleoptile bioassay with good results in a noteworthy effect on germination. The most active compounds were also tested on tomato seeds, heliannuol A (30) and leptocarpin (45) being the most active, with values similar to those of the commercial herbicide.

Microscale Synthesis, Reactions, and (Super 1)H NMR Spectroscopic Investigations of Square Planar Macrocyclic, Tetramido-N Co(III) Complexes Relevant to Green Chemistry

Science.gov (United States)

Watson, Tanya T.; Uffelman, Erich S.; Lee, Daniel W., III; Doherty, Jonathan R.; Schulze, Carl; Burke, Amy L.; Bonnema, Kristen, R.

2004-01-01

The microscale preparation, characterization, and reactivity of a square planar Co(III) complex that has grown out of a program to introduce experiments of relevance to green chemistry into the undergraduate curriculum is presented. The given experiments illustrate the remarkable redox and aqueous acid-base stability that make the macrocycles very…

Fungal Strains as Catalysts for the Biotransformation of Halolactones by Hydrolytic Dehalogenation with the Dimethylcyclohexane System

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Małgorzata Grabarczyk

2012-08-01

Full Text Available Bicyclic chloro-, bromo- and iodo-γ-lactones with dimethylcyclohexane rings were used as substrates for bioconversion by several fungal strains (Fusarium, Botrytis and Beauveria. Most of the selected microorganisms transformed these lactones by hydrolytic dehalogenation into the new compound cis-2-hydroxy-4,6-dimethyl-9-oxabicyclo[4.3.0]- nonan-8-one, mainly the (−-isomer. When iodo-γ-lactone was used as the substrate, two products were observed: a hydroxy-γ-lactone and an unsaturated lactone. The structures of all substrates and products were established on the basis of their spectral data. The mechanism of dehalogenation of three halolactones was also studied.

Simulations of charge transport in organic compounds

Energy Technology Data Exchange (ETDEWEB)

Vehoff, Thorsten

2010-05-05

We study the charge transport properties of organic liquid crystals, i.e. hexabenzocoronene and carbazole macrocycle, and single crystals, i.e. rubrene, indolocarbazole and benzothiophene derivatives (BTBT, BBBT). The aim is to find structure-property relationships linking the chemical structure as well as the morphology with the bulk charge carrier mobility of the compounds. To this end, molecular dynamics (MD) simulations are performed yielding realistic equilibrated morphologies. Partial charges and molecular orbitals are calculated based on single molecules in vacuum using quantum chemical methods. The molecular orbitals are then mapped onto the molecular positions and orientations, which allows calculation of the transfer integrals between nearest neighbors using the molecular orbital overlap method. Thus we obtain realistic transfer integral distributions and their autocorrelations. In case of organic crystals the differences between two descriptions of charge transport, namely semi-classical dynamics (SCD) in the small polaron limit and kinetic Monte Carlo (KMC) based on Marcus rates, are studied. The liquid crystals are investigated solely in the hopping limit. To simulate the charge dynamics using KMC, the centers of mass of the molecules are mapped onto lattice sites and the transfer integrals are used to compute the hopping rates. In the small polaron limit, where the electronic wave function is spread over a limited number of neighboring molecules, the Schroedinger equation is solved numerically using a semi-classical approach. The carbazole macrocycles form columnar structures arranged on a hexagonal lattice with side chains facing inwards, so columns can closely approach each other allowing inter-columnar and thus three-dimensional transport. We are able to show that, on the time-scales of charge transport, static disorder due to slow side chain motions is the main factor determining the mobility. The high mobility of rubrene is explained by two main

The human bitter taste receptor T2R38 is broadly tuned for bacterial compounds.

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Christophe Verbeurgt

Full Text Available T2R38 has been shown to be a specific bacterial detector implicated in innate immune defense mechanism of human upper airway. Several clinical studies have demonstrated that this receptor is associated with the development of chronic rhinosinusitis (CRS. T2R38 was previously reported to bind to homoserine lactones (HSL, quorum sensing molecules specific of Pseudomonas Aeruginosa and other gram negative species. Nevertheless, these bacteria are not the major pathogens found in CRS. Here we report on the identification of bacterial metabolites acting as new agonists of T2R38 based on a single cell calcium imaging study. Two quorum sensing molecules (Agr D1 thiolactone from Staphylococcus Aureus and CSP-1 from Streptococcus Pneumoniae and a list of 32 bacterial metabolites from pathogens frequently implicated in CRS were tested. First, we observed that HSL failed to activate T2R38 in our experimental system, but that the dimethylsulfoxide (DMSO, used as a solvent for these lactones may, by itself, account for the agonistic effect previously described. Secondly, we showed that both Agr D1 thiolactone and CSP-1 are inactive but that at least 7 bacterial metabolites (acetone, 2-butanone, 2-pentanone, 2-methylpropanal, dimethyl disulfide, methylmercaptan, γ-butyrolactone are able to specifically trigger this receptor. T2R38 is thus much more broadly tuned for bacterial compounds than previously thought.

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

Science.gov (United States)

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

2017-02-22

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

Transgenic plants producing the bacterial pheromone N-acyl-homoserine lactone exhibit enhanced resistance to the bacterial phytopathogen Erwinia carotovora.

Science.gov (United States)

Mäe, A; Montesano, M; Koiv, V; Palva, E T

2001-09-01

Bacterial pheromones, mainly different homoserine lactones, are central to a number of bacterial signaling processes, including those involved in plant pathogenicity. We previously demonstrated that N-oxoacyl-homoserine lactone (OHL) is essential for quorum sensing in the soft-rot phytopathogen Erwinia carotovora. In this pathogen, OHL controls the coordinate activation of genes encoding the main virulence determinants, extracellular plant cell wall degrading enzymes (PCWDEs), in a cell density-dependent manner. We suggest that E. carotovora employ quorum sensing to avoid the premature production of PCWDEs and subsequent activation of plant defense responses. To test whether modulating this sensory system would affect the outcome of a plant-pathogen interaction, we generated transgenic tobacco, producing OHL. This was accomplished by ectopic expression in tobacco of the E. carotovora gene expI, which is responsible for OHL biosynthesis. We show that expI-positive transgenic tobacco lines produced the active pheromone and partially complemented the avirulent phenotype of expI mutants. The OHL-producing tobacco lines exhibited enhanced resistance to infection by wild-type E. carotovora. The results were confirmed by exogenous addition of OHL to wild-type plants, which also resulted in increased resistance to E. carotovora.

Large-Scale Quantum Many-Body Perturbation on Spin and Charge Separation in the Excited States of the Synthesized Donor-Acceptor Hybrid PBI-Macrocycle Complex.

Science.gov (United States)

Ziaei, Vafa; Bredow, Thomas

2017-03-17

The reliable calculation of the excited states of charge-transfer (CT) compounds poses a major challenge to the ab initio community because the frequently employed method, time-dependent density functional theory (TD-DFT), massively relies on the underlying density functional, resulting in heavily Hartree-Fock (HF) exchange-dependent excited-state energies. By applying the highly sophisticated many-body perturbation approach, we address the encountered unreliabilities and inconsistencies of not optimally tuned (standard) TD-DFT regarding photo-excited CT phenomena, and present results concerning accurate vertical transition energies and the correct energetic ordering of the CT and the first visible singlet state of a recently synthesized thermodynamically stable large hybrid perylene bisimide-macrocycle complex. This is a large-scale application of the quantum many-body perturbation approach to a chemically relevant CT system, demonstrating the system-size independence of the quality of the many-body-based excitation energies. Furthermore, an optimal tuning of the ωB97X hybrid functional can well reproduce the many-body results, making TD-DFT a suitable choice but at the expense of introducing a range-separation parameter, which needs to be optimally tuned. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sesquiterpene lactone containing extracts from two cultivars of forage chicory (Cichorium intybus) show distinctive chemical profiles and in vitro activity against Ostertagia ostertagi

DEFF Research Database (Denmark)

Pena-Espinoza, Miguel Angel; Boas, Ulrik; Williams, Andrew

2015-01-01

The study investigated direct anthelmintic effects of sesquiterpene lactones (SL)-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars ‘Spadona’ and ‘Puna II’ were extracted using methanol/water. Total...

Synthesis, spectroscopic and biological activities studies of acyclic and macrocyclic mono and binuclear metal complexes containing a hard-soft Schiff base.

Science.gov (United States)

Abou-Hussein, Azza A A; Linert, Wolfgang

2012-09-01

Mono- and bi-nuclear acyclic and macrocyclic complexes with hard-soft Schiff base, H(2)L, ligand derived from the reaction of 4,6-diacetylresorcinol and thiocabohydrazide, in the molar ratio 1:2 have been prepared. The H(2)L ligand reacts with Co(II), Ni(II), Cu(II), Zn(II), Mn(II) and UO(2)(VI) nitrates, VO(IV) sulfate and Ru(III) chloride to get acyclic binuclear complexes except for VO(IV) and Ru(III) which gave acyclic mono-nuclear complexes. Reaction of the acyclic mono-nuclear VO(IV) and Ru(III) complexes with 4,6-diacetylresorcinol afforded the corresponding macrocyclic mono-nuclear VO(IV) and Ru(IIII) complexes. Template reactions of the 4,6-diacetylresorcinol and thiocarbohydrazide with either VO(IV) or Ru(III) salts afforded the macrocyclic binuclear VO(IV) and Ru(III) complexes. The Schiff base, H(2)L, ligand acts as dibasic with two NSO-tridentate sites and can coordinate with two metal ions to form binuclear complexes after the deprotonation of the hydrogen atoms of the phenolic groups in all the complexes, except in the case of the acyclic mononuclear Ru(III) and VO(IV) complexes, where the Schiff base behaves as neutral tetradentate chelate with N(2)S(2) donor atoms. The ligands and the metal complexes were characterized by elemental analysis, IR, UV-vis (1)H-NMR, thermal gravimetric analysis (TGA) and ESR, as well as the measurements of conductivity and magnetic moments at room temperature. Electronic spectra and magnetic moments of the complexes indicate the geometries of the metal centers are either tetrahedral, square planar or octahedral. Kinetic and thermodynamic parameters were calculated using Coats-Redfern equation, for the different thermal decomposition steps of the complexes. The ligands and the metal complexes were screened for their antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria, and Pseudomonas fluorescens as Gram-negative bacteria in addition to Fusarium oxysporum fungus. Most of the complexes exhibit

Differential Modulation of Transcription Factors and Cytoskeletal Proteins in Prostate Carcinoma Cells by a Bacterial Lactone

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Senthil R. Kumar

2018-01-01

Full Text Available The present study tested the effect of a bacterial lactone N-(3-oxododecanoyl-homoserine lactone (C12-HSL on the cytoskeletal and transcriptional genes and proteins in prostate adenocarcinoma (PA cells (DU145 and LNCaP and prostate small cell neuroendocrine carcinoma (SCNC PC3 cells including their cellular viability and apoptosis. Our data indicate that cell migration and colony formation were affected in the presence of C12-HSL. C12-HSL induced apoptosis and altered viability of both PA and SCNC cells in a concentration dependent manner as measured by fluorescence and chemiluminescence assays. Compared to PCa cells, noncancerous prostate epithelial cells (RWPE1 were resistant to modification by C12-HSL. Further, the viability of PC3 cells in 3D matrix was suppressed by C12-HSL treatment as detected using calcein AM fluorescence in situ. C12-HSL treatment induced cytoskeletal associated protein expression of vinculin and RhoC, which may have implications in cancer cell motility, adhesion, and metastasis. IQGAP protein expression was reduced in DU145 and RWPE1 cells in the presence of C12-HSL. C12-HSL decreased STAT3 phosphorylation in DU145 cells but increased STAT1 protein phosphorylation in PC3 and LNCaP cells. Overall, these studies indicate that C12-HSL can trigger changes in transcription factors and cytoskeletal proteins and thereby modulate growth and migration properties of PCa cells.

Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

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Bastian Barker Rasmussen

2014-11-01

Full Text Available Bacterial quorum sensing (QS and the corresponding signals, acyl homoserine lactones (AHLs, were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the environment has remained unclear. Three hundred and one Vibrionaceae strains were collected on a global research cruise and the prevalence and profile of AHL signals in this global collection were determined. AHLs were detected in 32 of the 301 strains using Agrobacterium tumefaciens and Chromobacterium violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl (OH-C6 and N-(3-hydroxy-decanoyl (OH-C10 homoserine lactones were the most common AHLs found in 17 and 12 strains, respectively. Several strains produced a diversity of different AHLs, including N-heptanoyl (C7 HL. AHL-producing Vibrionaceae were found in polar, temperate and tropical waters. The AHL profiles correlated with strain phylogeny based on gene sequence homology, however not with geographical location. In conclusion, a wide range of AHL signals are produced by a number of clades in the Vibrionaceae family and these results will allow future investigations of inter- and intra-species interactions within this cosmopolitan family of marine bacteria.

Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.

Science.gov (United States)

Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor

2013-08-01

The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 μg/mL reduced LPS-stimulated TNF-α production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9α-hydroxy-8β-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 μM) than the positive control parthenolide (IC50=4.79 μM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phytotoxicity Study on Bidens sulphurea Sch. Bip. as a Preliminary Approach for Weed Control.

Science.gov (United States)

da Silva, Bruna P; Nepomuceno, Mariluce P; Varela, Rosa M; Torres, Ascensión; Molinillo, José M G; Alves, Pedro L C A; Macías, Francisco A

2017-06-28

Farmers of the Franca region in Brazil observed that Bidens sulphurea was able to eliminate the Panicum maximum weed, which infected coffee plantations, without affecting the crop. In an effort to determine if the inhibitory effects observed were due to the presence of phytotoxic compounds from leaves and roots, a biodirected isolation and spectroscopic characterization has been carried out. The leaf dichloromethane and root acetone extracts were the most active, and the former appeared to be more phytotoxic to the target species, including four weeds. A total of 26 compounds were isolated from leaves and roots, and four of them are described here for the first time. The major compounds in the leaf extract are the sesquiterpene lactones costunolide, reynosin, and santamarine, and these showed marked inhibition. Amaranthus viridis and Panicum maximum were the most sensitive species of the weeds tested. These three phytotoxic lactones were also evaluated on A. viridis and P. maximum under hydroponic conditions. A. viridis was the most affected species with the three lactones, and santamarine was the most phytotoxic compound on both. This is the first time that the phytotoxicity of sesquiterpene lactones has been evaluated on hydroponic culture. The work described here is a preliminary approach for the use of B. sulphurea for weed control in agriculture, both as a cover crop and by use of its components as natural herbicide leads.

Magneto-electroluminescence effects in the single-layer organic light-emitting devices with macrocyclic aromatic hydrocarbons

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S.-T. Pham

2018-02-01

Full Text Available Magneto-electroluminescence (MEL effects are observed in single-layer organic light-emitting devices (OLEDs comprising only macrocyclic aromatic hydrocarbons (MAHs. The fluorescence devices were prepared using synthesized MAHs, namely, [n]cyclo-meta-phenylene ([n]CMP, n = 5, 6. The MEL ratio of the resulting OLED is 1%–2% in the spectral wavelength range of 400-500 nm, whereas it becomes negative (−1.5% to −2% in the range from 650 to 700 nm. The possible physical origins of the sign change in the MEL are discussed. This wavelength-dependent sign change in the MEL ratio could be a unique function for future single-layer OLEDs capable of magnetic-field-induced color changes.

Magneto-electroluminescence effects in the single-layer organic light-emitting devices with macrocyclic aromatic hydrocarbons

Science.gov (United States)

Pham, S.-T.; Ikemoto, K.; Suzuki, K. Z.; Izumi, T.; Taka, H.; Kita, H.; Sato, S.; Isobe, H.; Mizukami, S.

2018-02-01

Magneto-electroluminescence (MEL) effects are observed in single-layer organic light-emitting devices (OLEDs) comprising only macrocyclic aromatic hydrocarbons (MAHs). The fluorescence devices were prepared using synthesized MAHs, namely, [n]cyclo-meta-phenylene ([n]CMP, n = 5, 6). The MEL ratio of the resulting OLED is 1%-2% in the spectral wavelength range of 400-500 nm, whereas it becomes negative (-1.5% to -2%) in the range from 650 to 700 nm. The possible physical origins of the sign change in the MEL are discussed. This wavelength-dependent sign change in the MEL ratio could be a unique function for future single-layer OLEDs capable of magnetic-field-induced color changes.