Synthesis of Novel Mannich Derivatives of Bakuchiol as Apoptotic Inducer through Caspase Activation and PARP‐1 Cleavage in A549 Cells

A new series of bakuchiol 1 Mannich derivatives was synthesized by reaction with various substituted secondary amines. The analogs were evaluated for cytotoxicity against a panel of three different human cancer cell lines breast (MCF-7), colon (HCT-116) and lung (A549). Cytotoxicity screening results showed that many compounds displayed significant in vitro cytotoxic effects against different cancer cell lines. Compounds 9, 12, 14, 16, 17 and 21 showed promising cytotoxic effects compared to parent molecule 1 and among them compound 14 was found to be most potent analog with IC50 5 μM against all the cell lines examined. It was about 8-fold more potent against MCF-7 and A549 and 10-fold more potent against HCT-116 cell line in comparison to the parent molecule 1. Structure activity relationship (SAR) study of all synthesized derivatives was carried out. Further, compound 14 induced apoptosis in lung cancer cells (A549) through caspase activation followed by PARP-1 cleavage.