Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311

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.

Automated summary

Three antifungal macrolides were isolated from Streptomyces sp. ISID311, showing high antagonism against Escovopsis sp. and potent activity against Leishmania donovani. The planar structures were determined by NMR and MS analysis, with stereochemical assignments confirmed by bioinformatic analysis.