Proansamycin B derivatives from the post-PKS modification gene deletion mutant of Amycolatopsis mediterranei S699

J Antibiot (Tokyo). 2024 May;77(5):278-287. doi: 10.1038/s41429-024-00708-4. Epub 2024 Feb 26.

Abstract

Ten new proansamycin B congeners (1-10) together with one known (11) were isolated and characterized on the basis of 1D and 2D NMR spectroscopic and HRESIMS data from the Amycolatopsis mediterranei S699 ΔPM::rifR+rif-orf19 mutant. Compounds 8 and 9 featured with six-membered ring and five-membered ring hemiketal, respectively. Compounds 1, 2, and 9 displayed antibacterial activity against MRSA (methicillin-resistant Staphylococcus aureus), with the MIC (minimal inhibitory concentration) values of 64, 8, and 128 µg/mL, respectively. Compound 1 showed significant cytotoxicity against MDA-MB-231, HepG2 and Panc-1 cell lines with IC50 (half maximal inhibitory concentration) values of 2.3 ± 0.2, 2.5 ± 0.3 and 3.8 ± 0.5 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amycolatopsis* / genetics
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / isolation & purification
  • Anti-Bacterial Agents* / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Gene Deletion
  • Hep G2 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Methicillin-Resistant Staphylococcus aureus* / drug effects
  • Microbial Sensitivity Tests*
  • Molecular Structure

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents