2. Academic Validation
  3. Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311

Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311

  • Bioorg Med Chem. 2021 Feb 15:32:116016. doi: 10.1016/j.bmc.2021.116016.
Humberto E Ortega 1,  Vitor B Lourenzon 1,  Marc G Chevrette 2,  Leonardo L G Ferreira 3,  René F Ramos Alvarenga 4,  Weilan G P Melo 1,  Tiago Venâncio 5,  Cameron R Currie 6,  Adriano D Andricopulo 3,  Tim S Bugni 7,  Mônica T Pupo 8
Affiliations

Affiliations

  • 1 Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
  • 2 Wisconsin Institute for Discovery and Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI, United States.
  • 3 Laboratório de Química Medicinal e Computacional, Centro de Pesquisa e Inovação em Biodiversidade e Fármacos, Instituto de Física de São Carlos, Universidade de São Paulo, Av. João Dagnone 1100, São Carlos-SP 13563-120, Brazil.
  • 4 Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, United States.
  • 5 Department of Chemistry, Federal University of São Carlos, 13565-905 São Carlos, Brazil.
  • 6 Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, United States.
  • 7 Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI, United States. Electronic address: tim.bugni@wisc.edu.
  • 8 Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil. Electronic address: mtpupo@fcfrp.usp.br.
PMID: 33493972 DOI: 10.1016/j.bmc.2021.116016
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.

Figures