Polycyclic phenolic compounds from the Antarctic moss Polytrichum strictum and their potential in treating cancer and obesity.

A series of unreported polycyclic compounds (1-3), two undescribed benzonaphthoxanthenones (4 and 5), along with two known derivatives (6 and 7), were isolated from the Antarctic moss Polytrichum strictum (Polytrichaceae). The chemical structures of undescribed compounds were determined through extensive spectroscopic methods and ECD calculations. Compounds 1-6 were evaluated for their inhibitory effects on adipogenesis in preadipocyte 3T3-L1 and cytotoxicity against A549, HCT116, and MDA-MB-231 cancer cell lines, where compound 2 exhibited significance in anti-adipogenic activity and moderate to weak growth inhibitory effects against the tested cancer cell lines. Western blot analysis further confirmed that compound 2 inhibits adipogenesis through downregulation of PPARγ expression. Molecular docking and dynamics simulation studies were conducted to investigate the interaction between compound 2 and PPARγ, which functions as a master regulator of adipogenesis and is overexpressed in various tumors and cancers.