Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the endophytic fungus Byssochlamys spectabilis IMM0002 and their biological activities
| Autor: | Gui-Yang Xia, Zhao-Hui Sun, Ling-Yan Wang, Jun-Gui Dai, You-Cai Hu, Rui Li, Peng-Cheng Lin, Bo-Lin Qiu, Huawei Zhang, Jing-Fang Zhang, Guang-Bo Ge, Sheng Lin, Yu-Zhuo Wu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Staphylococcus aureus
Byssochlamys spectabilis Stereochemistry Dimer Byssochlamys Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Carboxylesterase Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Escherichia coli medicine Humans Enzyme Inhibitors Pharmacology Dose-Response Relationship Drug Molecular Structure biology 010405 organic chemistry Hydrogen bond Organic Chemistry General Medicine biology.organism_classification Antimicrobial Anti-Bacterial Agents 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry chemistry Docking (molecular) Polyketides Biocatalysis Edgeworthia chrysantha Carboxylic Ester Hydrolases Dimerization Two-dimensional nuclear magnetic resonance spectroscopy |
| Zdroj: | European Journal of Medicinal Chemistry. 145:717-725 |
| ISSN: | 0223-5234 |
| Popis: | Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon skeleton, and two new precursor derivatives, bysspectins B and C (2 and 3), were obtained from an organic extract of the endophytic fungus Byssochlamys spectabilis that had been isolated from a leaf tissue of the traditional Chinese medicinal plant Edgeworthia chrysantha, together with a known octaketide, paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR spectroscopic analysis. A plausible route for their biosynthetic pathway is proposed. Compounds 1–3 were tested for their antimicrobial activities. Only compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus with MIC values of 32 and 64 μg/mL, respectively. Further, the inhibitory effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were evaluated. The results demonstrated that bysspectin A (1) was a novel and highly selective inhibitor against hCE2 with the IC50 value of 2.01 μM. Docking simulation also demonstrated that active compound 1 created interaction with the Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen bonding, revealing its highly selective inhibition toward hCE2. |
| Databáze: | OpenAIRE |
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