Alkaloids from the nearly ripe fruits of Tetradium ruticarpum and inhibitory effects on colorectal cancer cells.
TL;DR
It is validated that the anti-colorectal cancer activity of the new compound 6 was associated with the induction of ferroptosis, and support compound 6 as a valuable candidate worthy of further development as an antitumor agent.
Abstract
Tetradium ruticarpum is a commonly used medicinal herb in China that has been widely applied to alleviate clinical symptoms such as abdominal distension, abdominal pain, vomiting, and diarrhea. In the present study, total alkaloids were prepared from Tetradium ruticarpum by hydrochloric acid extraction. From these total alkaloids, 34 alkaloids were isolated and determined by detailed analysis of NMR, HRESIMS, and ECD spectroscopic data, among which eight alkaloids were previously undescribed compounds (1-8). Notably, compound 1 represents a rare plant-derived alkaloid skeleton, featuring a unique structure consisting of a quinazolin-4(3H)-one moiety and a 3'-hydroxy-2'-oxoindoline moiety linked via C-2 and C-3'. The antiproliferative activity of all isolated compounds were evaluated and primary structure-activity relationships (SARs) were further clarified. Furthermore, plausible biosynthetic pathways for compound 1 were proposed. Preliminary antitumor screening indicated that the new compound 6, together with several known alkaloids (compounds 12, 14, and 18-21) displayed promising anti-colorectal cancer activity. Furthermore, we validated that the anti-colorectal cancer activity of the new compound 6 was associated with the induction of ferroptosis. Collectively, these findings support compound 6 as a valuable candidate worthy of further development as an antitumor agent.