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.
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The authors thank Dr. I. Momose and Mr. S. Ohba for technical assistance and discussion. The authors also thank the Molecular Profiling Committee, Grant-in-Aid for Scientific Research on Innovative Areas “Advanced Animal Model Support (AdAMS)” from The Ministry of Education, Culture, Sports, Science and Technology, Japan (JSPS KAKENHI Grant Number JP 16H06276). This work was supported in part by grants from JSPS KAKENHI Grant Number 17K08777.
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Kohda, Y., Sakamoto, S., Umekita, M. et al. Isolation of new derivatives of the 20-membered macrodiolide bispolide from Kitasatospora sp. MG372-hF19. J Antibiot 75, 77–85 (2022). https://doi.org/10.1038/s41429-021-00492-5