Synthesis and biological evaluation of novel withangulatin A derivatives as potential anticancer agents

Novel withangulatin A (WA) derivatives were synthesized and evaluated for antiproliferative activity against four human cancer cell lines (U2OS, MDA-MB-231, HepG2, and A549). Among these derivatives, 10 exhibited the most potent antiproliferative activity, with an IC50 value of 74.0 nM against the human breast cancer cell line MDA-MB-231 and potency that was 70-fold that of WA (IC50 = 5.22 mu M). Moreover, 10 caused G2-phase cell cycle arrest in a concentration-dependent manner and induced the apoptosis of MDA-MB-231 cells by increasing intracellular reactive oxygen species (ROS). Compound 10 showed a high selectivity index (SI = 267.03) for breast cancer MDA-MB-231 cells. These results suggest that 10 is a promising anticancer agent.

Automated summary

Novel derivatives of withangulatin A (WA) were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines, with compound 10 showing the most potent activity against the human breast cancer cell line MDA-MB-231. Compound 10 also demonstrated a high selectivity index for breast cancer MDA-MB-231 cells, indicating its potential as a promising anticancer agent.