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

Abstract

A diverse range of α-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 α-cyano bis(indolyl)chalcones involves readily available starting materials, catalytic L-proline, environmentally benign and metal-free conditions. The prepared eighteen α-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 α-cyano bis(indolyl)chalcones 21a (3.9 μM), 21c (7.5 μM), 21i (2.2 μM) and 21o (5.9 μM) displayed good cytotoxicity against C4-2 cells, whereas, derivatives 21c (1.23 μM), 21h (5.23 μM), and 21l (2.5 μM) showed selective cytotoxicity against 22Rv1 cells. With broad spectrum of activity (0.98–5.6 μM), 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.