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Chembiochem : a European Journal of... Oct 2008The overproduction, purification, and in vitro characterization of the polyene glycosyltransferases (GTs) AmphDI and NysDI are reported. A novel nucleotidyltransferase...
The overproduction, purification, and in vitro characterization of the polyene glycosyltransferases (GTs) AmphDI and NysDI are reported. A novel nucleotidyltransferase mutant (RmlA Q83D) for the chemoenzymatic synthesis of unnatural GDP-sugar donors in conjunction with polyene GT-catalyzed sugar exchange/reverse reactions allowed the donor and acceptor specificities of these novel enzymes to be probed. The evaluation of polyene GT aglycon and GDP-sugar donor specificity revealed some tolerance to aglycon structural diversity, but stringent sugar specificity, and culminated in new polyene analogues in which L-gulose or D-mannose replace the native sugar D-mycosamine.
Topics: Biocatalysis; Glycosides; Glycosyltransferases; Guanosine Diphosphate; Molecular Structure; Polyenes; Streptomyces
PubMed: 18798210
DOI: 10.1002/cbic.200800349 -
Natural Product Research Jan 2021A new fusicoccane diterpene, pinophicin A (, and a new polyene, pinophol A (), were isolated from the plant endophytic fungus obtained from the aerial parts of . The...
A new fusicoccane diterpene, pinophicin A (, and a new polyene, pinophol A (), were isolated from the plant endophytic fungus obtained from the aerial parts of . The structures and relative configurations of - were determined by the analysis of extensive spectroscopic data, chemical method, and comparison with known compounds. Compound exhibited weak antibacterial activity against B with an MIC value of 50 μg/mL.
Topics: Anti-Bacterial Agents; Diterpenes; Drug Evaluation, Preclinical; Endophytes; Microbial Sensitivity Tests; Molecular Structure; Plant Components, Aerial; Polyenes; Salvia miltiorrhiza; Talaromyces
PubMed: 31140306
DOI: 10.1080/14786419.2019.1616727 -
Antimicrobial Agents and Chemotherapy Apr 1975A new species of Actinoplanes, which has been deposited with the designation NRRL 5325 at the Northern Utilization Research and Development Division of the U. S....
A new species of Actinoplanes, which has been deposited with the designation NRRL 5325 at the Northern Utilization Research and Development Division of the U. S. Department of Agriculture, produces a polyene antifungal complex designated as Sch 16656. The complex, consisting of one major and three minor components, is isolated from the fermentation broth by a solvent extraction procedure and purified by precipitation methods. The major component is a heptaene and is highly active in vitro and in vivo against Candida albicans. It is active also against strains of Torulopsis and is significantly more potent orally than candicidin in mice against Candida infections.
Topics: Actinomycetales; Animals; Antifungal Agents; Fermentation; Mice; Polyenes
PubMed: 1147581
DOI: 10.1128/AAC.7.4.457 -
Antibiotiki I Khimioterapiia =... Aug 1988
Comparative Study Review
Topics: Antifungal Agents; Cell Membrane Permeability; Fungi; Polyenes; Structure-Activity Relationship
PubMed: 3058066
DOI: No ID Found -
Chemistry (Weinheim An Der Bergstrasse,... Jan 2017We report a full account on the development of a unique cationic polyene cyclization for the total synthesis of the tetracyclic meroterpenoid (-)-cyclosmenospongine. A...
We report a full account on the development of a unique cationic polyene cyclization for the total synthesis of the tetracyclic meroterpenoid (-)-cyclosmenospongine. A highly convergent three-component coupling strategy enabled rapid access to individual cyclization precursors that were tested for their reactivity. The successful transformation generates three rings and sets four consecutive stereocenters in a single operation proceeding in a highly efficient manner to give exclusively the trans-decalin framework. In addition, we found that the enol ether geometry and the relative configuration of C3 and C8 are crucial for the success of the polyene cyclization.
Topics: Crystallography, X-Ray; Cyclization; Molecular Conformation; Polyenes; Quinones; Sesquiterpenes; Stereoisomerism; Terpenes
PubMed: 27859768
DOI: 10.1002/chem.201605029 -
Journal of Natural Products Sep 2004Reinvestigation of the production of the unusual polyene carboxylic acid serpentene (1a) from Streptomycessp. Tü 3851 revealed the presence of additional polyene...
Reinvestigation of the production of the unusual polyene carboxylic acid serpentene (1a) from Streptomycessp. Tü 3851 revealed the presence of additional polyene carboxylic acids. The methyl esters of the new all-trans serpentene (2) and four new dicarboxylic acids (3-6) were isolated after methylation of the isolated polyene fraction. The dicarboxylic acids might result from omega- and beta-oxidation of the parent compounds 1 and 2.
Topics: Carboxylic Acids; Dicarboxylic Acids; Esters; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oxidation-Reduction; Polyenes; Stereoisomerism; Streptomyces
PubMed: 15387680
DOI: 10.1021/np049852t -
Molecules (Basel, Switzerland) Mar 2023Two previously unreported onnamide analogs, 2- and 6-onnamides A ( and ), were isolated from the marine sponge collected at Amami-Oshima Is., Kagoshima Prefecture,...
Two previously unreported onnamide analogs, 2- and 6-onnamides A ( and ), were isolated from the marine sponge collected at Amami-Oshima Is., Kagoshima Prefecture, Japan. Structures of compounds and were elucidated by spectral analysis. Structure-activity relationships (SARs) for effects on histone modifications and cytotoxicity against HeLa and P388 cells were characterized. The geometry in the polyene systems of onnamides affected the histone modification levels and cytotoxicity.
Topics: Animals; Humans; Theonella; Porifera; Pyrans; HeLa Cells; Polyenes; Molecular Structure
PubMed: 36985496
DOI: 10.3390/molecules28062524 -
Antimicrobial Agents and Chemotherapy Apr 1977Polyene antifungal antibiotics produce various degrees of membrane damage in sheep erythrocytes in vitro. Mediocidin, filipin, amphotericin B, and candicidin were found...
Polyene antifungal antibiotics produce various degrees of membrane damage in sheep erythrocytes in vitro. Mediocidin, filipin, amphotericin B, and candicidin were found to result in greater damage than nystatin, pimaricin, and amphotericin B methyl ester. The degree of sensitivity of the cells varied by 100-fold for mediocidin verus amphotericin B methyl ester as measured by curves of hemoglobin release versus drug concentration. In erythrocytes prelabeled with radioactive chromium, release of the isotope through polyene-damaged cell membranes was found to occur at lower drug concentrations than measurable hemoglobin release, and the percentage of isotope released at the highest drug dose was consistently greater than the percentage of hemoglobin released. Thus, the isotope assay is a more sensitive indicator of polyene-induced membrane damage in the test system. These significant differences in release of molecules through polyene-induced membrane lesions indicate the complex nature of the binding and further interactions of this class of drugs with the plasma membrane.
Topics: Antifungal Agents; Chromium; Chromium Radioisotopes; Erythrocytes; Hemoglobins; Hemolysis; Humans; Polyenes
PubMed: 856027
DOI: 10.1128/AAC.11.4.675 -
Drug Design, Development and Therapy 2023Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year... (Review)
Review
Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.
Topics: Pregnancy; Female; Humans; Candidiasis, Vulvovaginal; Fluconazole; Antifungal Agents; Triterpenes; Candida albicans; Azoles; Polyenes
PubMed: 36785761
DOI: 10.2147/DDDT.S339349 -
Journal of the American Chemical Society Aug 2017Results of kinetic experiments and quantum chemical computations on a series of platinum-promoted polycyclization reactions are described. Analyses of these results...
Results of kinetic experiments and quantum chemical computations on a series of platinum-promoted polycyclization reactions are described. Analyses of these results reveal a reactivity model that reaches beyond the energetics of the cascade itself, incorporating an ensemble of pre-cyclization conformations of the platinum-alkene reactant complex, only a subset of which are productive for bi- (or larger) cyclization and lead to products. Similarities and differences between this scenario, including reaction coordinates for polycyclization, for platinum- and enzyme-promoted polycyclization reactions are highlighted.
Topics: Alkenes; Biomimetics; Catalysis; Cyclization; Models, Molecular; Molecular Conformation; Platinum; Polyenes; Squalene; Stereoisomerism
PubMed: 28719198
DOI: 10.1021/jacs.7b05381