Gause Institute of New Antibiotics, Moscow, 119021, Russian Federation.
Lomonosov Moscow State University, Moscow, 119991, Russian Federation.
Nat Prod Res. 2020 Nov;34(21):3073-3081. doi: 10.1080/14786419.2019.1608540. Epub 2019 May 10.
We describe the synthesis of epi-oligomycin A, a (33)-diastereomer of the antibiotic oligomycin A. The structure of (33)-oligomycin A was determined by elemental analysis, spectroscopic studies, including 1D and 2D NMR spectroscopy, and mass spectrometry. Isomerization of C33 hydroxyl group led to minor changes in the potency against , , and filamentous fungi whereas the activity against decreased by approximately 20-fold compared to oligomycin A. We observed that 33-epi-oligomycin A had the same activity on the human leukemia cell line K562 as oligomycin A but was more potent for the multidrug resistant subline K562/4. Non-malignant cells were less sensitive to both oligomycin isomers. Finally, our results pointed at the dependence of the cytotoxicity of oligomycins on oxygen supply.
我们描述了（33）-表寡霉素 A 的合成，这是抗生素寡霉素 A 的一种差向异构体。（33）-寡霉素 A 的结构通过元素分析、包括 1D 和 2D NMR 光谱以及质谱研究来确定。C33 羟基的异构化导致其对 、 和丝状真菌的活性略有变化，而与寡霉素 A 相比，其对 的活性降低了约 20 倍。我们观察到 33-表寡霉素 A 在人白血病细胞系 K562 上的活性与寡霉素 A 相同，但对多药耐药亚系 K562/4 更有效。两种寡霉素异构体对非恶性细胞的敏感性较低。最后，我们的结果表明寡霉素的细胞毒性依赖于氧的供应。
