Abstract
Although, the structure of oligomycin A (1) was confirmed by spectroscopic and chemical evaluations, some crystallographic data cast doubt on the originally adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1-propenyl). To clarify this matter we synthesized and evaluated 33-dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O-mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin (2) and results of quantum chemical calculations have shown that this derivative exists in the keto rather than in the enol tautomer 2a. The in vitro antimicrobial activity of 2 was approximately two times weaker in comparison with oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp. strains and similar activity against certain filamentous fungi. The docking binding estimate of 2 with FOF1ATP synthase showed a slight decrease in binding affinity for 2 when compared with oligomycin A; that correlated with its activity against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in vitro antiproliferative activities of 2 are also discussed.
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Acknowledgements
This study was supported by grants by the Russian Science Foundation (agreement no. 15-15-00141). We thank YN Luzikov for the help with NMR, NM Maliutina for HPLC and EN Bichkova (Gause Institute of New Antibiotics) for IR and UV analyses.
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Lysenkova, L., Saveljev, O., Grammatikova, N. et al. Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A. J Antibiot 70, 871–877 (2017). https://doi.org/10.1038/ja.2017.48
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DOI: https://doi.org/10.1038/ja.2017.48
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