Design and Synthesis of Novel Caudatin Derivatives Containing Arylacryloyl and Quinolyl Substituents With Anticancer Activity.

Caudatin (1) represents one of major C21-steroids isolated from Cynanchum otophyllum. Thirty-one novel caudatin derivatives with arylacryloyl (1a-1w) and quinolyl (2a-2h) substituents were synthesized and structurally characterized by spectroscopic analysis. Their anticancer activities were evaluated against four human cancer cell lines (MCF-7, H1299, HeLa, and HepG2). Most compounds exhibit significant antiproliferative effects, among which 1b and 2h demonstrated broad-spectrum activity with IC50 values of 8.54-12.12 and 11.43-14.25 uM, respectively. Further mechanistic studies showed that 1b induced marked apoptosis in HepG2 cells and modulated cell cycle distribution, with a higher percentage of cells accumulating in the G0/G1 phase at increased concentrations. Overall, these findings indicate that caudatin derivatives bearing arylacryloyl and quinolyl moieties constitute a preliminary chemical framework for the development of antitumor candidates for caudatin-like natural products.