Bisabosqual D

Seven undescribed phenylspirodrimane derivatives, stachybochartins A-G (1-7), and four known analogues (8-11) were isolated from the endophytic fungus Stachybotrys chartarum obtained from Pinellia ternata. Stachybochartins A-D are four rare C-C-coupled dimeric derivatives and stachybochartin G features a seco-bisabosqual skeleton. Their structures and configurations were elucidated via spectroscopic analysis, electronic circular dichroism (ECD) calculations, the ECD exciton chirality method and the modified Mosher's method. Stachybochartins A-D and G displayed cytotoxic activities against MDA-MB-231 breast cancer cells and U-2OS osteosarcoma cells, with IC50 values ranging from 4.5 to 21.7 μM. Stachybochartins C and G exerted strong anti-proliferative activities against U-2OS cells in concentration- and time-dependent manners and induced apoptosis.

In the course of screening for yeast squalene synthase inhibitors, bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260. The related compounds bisabosquals B, C and D were also isolated from Stachybotrys ruwenzoriensis RF-6853. Bisabosquals inhibited squalene synthases. IC50 values of bisabosqual A against the microsomal squalene synthases from Saccharomyces cerevisiae, Candida albicans, HepG2 cell and rat liver were 0.43, 0.25, 0.95 and 2.5 microg/ml, respectively. Bisabosqual C exhibited inhibitory activities similar to bisabosqual A. Bisabosqual A showed broad spectrum antifungal activity in vitro.

The squalene synthase inhibitor bisabosqual A was isolated from the culture broth of Stachybotrys sp. RF-7260, and its structure was determined on the basis of spectroscopic methods including detailed 2D NMR analyses. The structures of bisabosquals B, C and D isolated from Stachybotrys ruwenzoriensis RF-6853 were determined by spectroscopic methods and chemical reactions. The absolute stereochemistry of bisabosquals A, B and D was determined by X-ray crystallographic analysis. They have novel cis-fused tetracyclic structures with a bisabolane-type sesquiterpene and phenol moieties.