Published: Jan. 1, 2023

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide sulfonate TET derivatives were designed, synthesized, evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, β-unsaturated carbonyl group exhibited most potent against all tested cell lines (including Hela, HCT116, HepG2, MCF-7, SHSY5Y), as well negligible normal LO2 HEK293. Additionally, effectively inhibited HCT116 CT26 in vitro increased proportion G2/M phase, activated mitochondrial apoptosis pathway, induced colon cancer by suppressing PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that is potentially bound to residues stronger binding affinity than TET. Ultimately, dramatically suppressed growth xenograft model, without noticeable visceral detected high-dose group. summary, might new insights designing inhibitors be candidate treatment.

Language: Английский