Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
Wisconsin Institute for Discovery and Department of Plant Pathology, University of Wisconsin-Madison, Madison, WI, United States.
Bioorg Med Chem. 2021 Feb 15;32:116016. doi: 10.1016/j.bmc.2021.116016. Epub 2021 Jan 12.
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 IC values of 2.32, 0.091 and 0.073 µM, respectively, with high selectivity indexes.
从与真菌培养蚂蚁共生的链霉菌属 ISID311 中分离到三种抗真菌大环内酯类化合物：cyphomycin（1）、caniferolide C（2）和 GT-35（3）。这些化合物的平面结构通过 1 和 2D NMR 数据和 MS 分析确定。通过 Kishi 的通用 NMR 数据库方法、NOE/ROE 分析和耦合常数分析，并与相关化合物的 NMR 数据进行比较，确定了 1-3 的相对构型。对 cyphomycin 生物合成基因簇的详细生物信息学分析证实了立体化学的归属。化合物 1-3 对不同菌株的 Escovopsis sp. 表现出高度拮抗作用，Escovopsis sp. 是专门针对真菌培养蚂蚁系统的病原菌真菌。化合物 1-3 对体内利什曼原虫的内阿米巴体也表现出很强的抗原虫活性，IC 值分别为 2.32、0.091 和 0.073µM，具有很高的选择性指数。
