1. Isolation of new derivatives of the 20-membered macrodiolide bispolide from Kitasatospora sp. MG372-hF19
- Author
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Yasuko Kohda, Shuichi Sakamoto, Maya Umekita, Tomoyuki Kimura, Yumiko Kubota, Rie Arisaka, Yuko Shibuya, Hideyuki Muramatsu, Ryuichi Sawa, Shingo Dan, Manabu Kawada, and Masayuki Igarashi
- Subjects
Methicillin-Resistant Staphylococcus aureus ,Pharmacology ,Antibiotics, Antineoplastic ,Magnetic Resonance Spectroscopy ,Alkylation ,Molecular Structure ,Streptomycetaceae ,Vancomycin Resistance ,Microbial Sensitivity Tests ,Crystallography, X-Ray ,Anti-Bacterial Agents ,Actinobacteria ,A549 Cells ,Cell Line, Tumor ,Drug Discovery ,Humans ,Macrolides ,Drug Screening Assays, Antitumor ,Enterococcus - Abstract
New three macrocyclic diolides, named bispolides C-E (1-3), were isolated from a fermentation broth of the actinomycete strain MG372-hF19, which produces an indole glycoside and leptomycins as we reported previously. The absolute structures of compounds 1-3 were elucidated by NMR and X-ray crystallography. Compounds 1-3 diverge from the known nine bispolides in their different alkylation patterns on the 20-membered macrocyclic diolide skeleton and the side chain in their planar structures. Furthermore, compounds 1-3 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci and cytotoxic activity against human cancer cell lines. Among them, compound 3 has the most potent biological activities against bacteria and tumor cells. Additionally, using a membrane-potential-sensitive fluorescence probe, we found that compounds 1-3 and elaiophylin have a similar effect on membrane potential in A549 human lung cancer cells.
- Published
- 2021