Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311

Bioorg Med Chem. 2021 Feb 15;32:116016. doi: 10.1016/j.bmc.2021.116016. Epub 2021 Jan 12.

Abstract

Three antifungal macrolides cyphomycin (1), caniferolide C (2) and GT-35 (3) were isolated from Streptomyces sp. ISID311, a bacterial symbiont associated with Cyphomyrmex fungus-growing ants. The planar structures of these compounds were established by 1 and 2D NMR data and MS analysis. The relative configurations of 1-3 were established using Kishi's universal NMR database method, NOE/ROE analysis and coupling constants analysis assisted by comparisons with NMR data of related compounds. Detailed bioinformatic analysis of cyphomycin biosynthetic gene cluster confirmed the stereochemical assignments. Compounds 1-3 displayed high antagonism against different strains of Escovopsis sp., pathogen fungi specialized to the fungus-growing ant system. Compounds 1-3 also exhibited potent antiprotozoal activity against intracellular amastigotes of the human parasite Leishmania donovani with IC50 values of 2.32, 0.091 and 0.073 µM, respectively, with high selectivity indexes.

Keywords: Fungus-growing ants; Leishmania donovani; Macrolides; Polyketides; Streptomyces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / isolation & purification
  • Antiprotozoal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Leishmania donovani / drug effects*
  • Macrolides / chemistry
  • Macrolides / isolation & purification
  • Macrolides / pharmacology*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Streptomyces / chemistry*
  • Structure-Activity Relationship

Substances

  • Antiprotozoal Agents
  • Macrolides