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Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311

Authors:

Ortega, Humberto E. [1, 2] ; Lourenzon, Vitor B. [1] ; Chevrette, Marc G. [3, 4] ; Ferreira, Leonardo L. G. [5] ; Alvarenga, Rene F. Ramos [6, 7] ; Melo, Weilan G. P. [1] ; Venancio, Tiago [8] ; Currie, Cameron R. [9] ; Andricopulo, Adriano D. [5] ; Bugni, Tim S. [6] ; Pupo, Monica T. [1]

 

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 antipmtozoal activity against intracellular amastigotes of the human parasite Leishmania donovani with IC50 values of 2.32, 0.091 and 0.073 mu M, respectively, with high selectivity indexes.

 

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

 

Link to article:   https://www.sciencedirect.com/science/article/abs/pii/S0968089621000249?via%3Dihub