Withanolide derivatives from Physalis angulata var. villosa and their cytotoxic activities

Phytochemical study on the leaves and twigs of Physalis angulata. var. villosa led to 23 withanolide derivatives, including a novel 13, 20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2−4). Architecturally, physalinin A (1) represents the first 13, 20-γ-lactone type B withanolide derivative. Their structures were established through various spectroscopic data and quantum chemical calculations. All the isolates were evaluated for their antiproliferative activities against four human cancer cells (HEL, HCT-116, Colo320DM, and MDA-MB-231). Eight withanolide derivatives (2, 5–8, 14, 15, and 23) exhibited significant inhibitory effects on tested cell lines with IC₅₀ values of 0.18 ± 0.03 to 17.02 ± 0.21 μM. The structure−activity relationship discussion implied that epoxide ring could improve their anti-cancer activity. This study indicated that withanolides could be applied to treat and prevent cancer due to their potent antiproliferative activities.