New liposidomycin congeners produced by Streptomyces sp. TMPU-20A065, anti-Mycobacterium avium complex agents with therapeutic efficacy in a silkworm infection model

Abstract

Three new liposidomycin congeners (1, 2, and 4), together with 14 known liposidomycins (3 and 5–17), were isolated from the culture broth of Streptomyces sp. TMPU-20A065 as anti-Mycobacterium avium complex agents. The structures of liposidomycins were elucidated by spectroscopic analyses, including NMR and MS. Compounds 1, 2, and 4 belong to type-I liposidomycin-containing sulfate groups and methylglutaric acid, each with a different acyl side chain in the structure. Compounds 1–17 exhibited in vitro anti-M. avium and M. intracellulare activities with MIC values ranging between 2.0 and 64 μg ml−1. Furthermore, 1–17 exerted potent therapeutic effects in an in vivo-mimic silkworm infection model with ED50 values ranging between 0.12 and 3.7 μg larva−1 g−1.