Synthesis, antimicrobial and antiproliferative properties of epi-oligomycin A, the (33 S)-diastereomer of oligomycin A

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 (33S)-diastereomer of the antibiotic oligomycin A. The structure of (33S)-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 Aspergillus niger, Candida spp., and filamentous fungi whereas the activity against Streptomyces fradiae 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.

Keywords: (33S)-oligomycin A; 33-O-mesyloligomycin; Oligomycin A; antimicrobial activity; cytotoxicity; epimers; mitochondrial F1FO ATP-synthase.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Aspergillus niger / drug effects
  • Candida / drug effects
  • Cell Proliferation / drug effects
  • Dogs
  • Drug Resistance, Neoplasm
  • Humans
  • K562 Cells
  • MCF-7 Cells
  • Madin Darby Canine Kidney Cells
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Oligomycins / chemical synthesis*
  • Oligomycins / pharmacology*
  • Stereoisomerism
  • Streptomyces / drug effects
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • Oligomycins
  • oligomycin A

Supplementary concepts

  • Streptomyces fradiae