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

Two heterocycle-fused cytochalasan homodimers, bisaspochalasins D () and E (), were isolated from an endophytic . Their chemical structures were elucidated using a combination of HRESIMS, NMR, theoretical calculations, and crystallographic techniques. Bisaspochalasin D () is dimerized by the first reported naturally occurring triple heterobridged 3,8-dioxa-6-azabicyclo[3.2.1]octane framework, while bisaspochalasin E () 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 IC 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.