Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents

Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivative A17 (namely tumulosic acid, also found in Poria cocos), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC50 values of 7.36 & PLUSMN; 0.98 and 2.50 & PLUSMN; 0.15 mu M, respectively. Further pharmacological analysis demonstrated that A17 induced HSC-2 cell cycle arrest at the S phase, cell apoptosis, and autophagy. Western blotting confirmed the regulatory effects of A17 on cell cycle arrest-, apoptosis-, and autophagy-related proteins expression. In addition, A17 regulated the AKT and AMPK pathways in HSC-2 cells. These results demonstrated that A17 possesses great potential as an anticancer agent. [GRAPHICS] .<br />