<sc>l</sc>-Proline catalysed synthesis and in silico studies of novel α-cyano bis(indolyl)chalcones as potential anti-cancer agents

A diverse range of alpha-cyano bis(indolyl)chalcones (21a-r) were synthesized in high yields (90-95%) through the l-proline catalysed reaction of appropriate aldehydes and 3-cyanoacetylindoles. Formation of alpha-cyano bis(indolyl)chalcones involves readily available starting materials, catalytic l-proline, environmentally benign and metal-free conditions. The prepared eighteen alpha-cyano bis(indolyl)chalcones 21a-r were screened against prostate, breast, epithelial cancer cells and found to be non-cytotoxic to normal HEK293 cells. The alpha-cyano bis(indolyl)chalcones 21a (3.9 mu M), 21c (7.5 mu M), 21i (2.2 mu M) and 21o (5.9 mu M) displayed good cytotoxicity against C4-2 cells, whereas, derivatives 21c (1.23 mu M), 21h (5.23 mu M), and 21l (2.5 mu M) showed selective cytotoxicity against 22Rv1 cells. With broad spectrum of activity (0.98-5.6 mu M), the compound 21j was found to increase the endogenous level of ROS, upregulate the level of p-53 and c-jun besides mitochondrial dysfunction, cause apoptosis.