Synthesis, cytotoxic activity, and 2D‐ and 3D‐<scp>QSAR</scp> studies of 19‐carboxyl‐modified novel isosteviol derivatives as potential anticancer agents

Abstract

Two series of novel acylthiosemicarbazide and oxadiazole fused‐isosteviol derivatives were synthesized based on the 19‐carboxyl modification. The target compounds were evaluated for their cytotoxicities against three cancer cell lines ( HCT ‐116, HGC ‐27, and JEKO ‐1) using an MTT assay. Lead compounds from the acylthiosemicarbazides ( 4 ) showed IC 50 values in the lower micromolar range. For example, compounds ( 4i , 4l , 4m , 4r, and 4s ) exhibited significant inhibitory activities against the three cell lines with IC 50 values of 0.95–3.36 μ m . Furthermore, 2D‐ HQSAR and 3D‐topomer Co MFA analyses were established, which could be used to develop second generation of isosteviol derivatives as anticancer agents.