Bisaspochalasins D and E: Two Heterocycle-Fused Cytochalasan Homodimers from an Endophytic Aspergillus flavipes

J Org Chem. 2021 Apr 15. doi: 10.1021/acs.joc.1c00425. Online ahead of print.

ABSTRACT

Two heterocycle-fused cytochalasan homodimers, bisaspochalasins D (1) and E (2), were isolated from an endophytic Aspergillus flavipes. Their chemical structures were elucidated using a combination of HRESIMS, NMR, theoretical calculations, and crystallographic techniques. Bisaspochalasin D (1) is dimerized by the first reported naturally occurring triple heterobridged 3,8-dioxa-6-azabicyclo[3.2.1]octane framework, while bisaspochalasin E (2) employs a pyrrole ring as the linking moiety. Possible dimerization mechanisms of bisaspochalasins D and E were proposed. The bioassay screening revealed that bisaspochalasin D showed cytotoxic activities against five cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) with IC50 values ranging from 4.45 to 22.99 μM. Additionally, bisaspochalasin D exhibited neurotrophic activities in a PC12 cell-based assay. At a concentration of 10 μM, bisaspochalasin D can promote neurite growth by inducing a differentiation rate of 12.52% for PC12 cells.

PMID:33855851 | DOI:10.1021/acs.joc.1c00425

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