Synthesis, cytotoxicity and HQSAR study of amides-fused isosteviol derivatives as potential anti-colorectal cancer agents

Abstract

A series of novel amide-fused isosteviol derivatives were designed and synthesized. Their cytotoxicities in vitro against HCT-116 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxicity. Especially, the compound 33 revealed the most potent inhibitory activity with IC₅₀ value of 7.663 ± 0.211 μM. Based on these bioactivity data, hologram quantitative structure–activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r² = 0.866, q² = 0.662 and r²_pred = 0.762) was achieved. In addition, the contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule.