Cytochalasans with Inhibitory Activity against NPC1L1 from the Endophytic Fungus <i>Chaetomium nigricolor</i> F5
Chen-Chen Gu, Jun Zeng, Xiao-Ping Peng, Yan-Jun Sun, Shuang-Zhi Yuan, Xiu-Ning Wang, Renshuai Zhang, Hong‐Xiang Lou, Gang Li
Abstract
Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus Chaetomium nigricolor F5 guided the isolation of five novel cytochalasans, chamisides B–F ( 1–5 ), and two known ones, chaetoconvosins C and D ( 6 and 7 ). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds 1–3 share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system. Remarkably, compound 5 with a relatively flexible side chain showed promising inhibition activity against the cholesterol transporter protein Niemann-Pick C1-like 1 (NPC1L1), expanding the function of cytochalasans.