Abstract
A three-component, [3 + 2]-cycloaddition/annulation domino protocol is described for the synthesis in excellent yield of a polycyclic cage-like heterocyclic hybrid (PCHH) that comprises various advantaged structural units viz., alpha,beta-unsaturated ketone moiety, 4-pyridinone and pyrroloisoquinoline in a cage-like framework. The antitumor activity of PCHH on human breast (MCF7), colon (HCT116), cervical (JURKAT) and lung (NCI-H460) malignant cell lines inhibited the propagation of all cell lines. This hybrid molecule displayed increased broad-spectrum anticancer activity with higher doses of PCHH. Furthermore, the compound induced 45.21% of early apoptosis and 46.32% of late apoptosis in the Jurkat cancer cell line. Cell cycle analysis showed that this cage-like compound caused cell cycle arrest of Jurkat cells at the S phase and sub G0/G1 phase. Additionally, it led to increased DNA fragmentation and mitochondrial membrane permeabilization through activation of caspase-3 enzyme. Present investigation demonstrates the specific cytotoxic activity of the cage-like compound and the induction of apoptosis through the intrinsic pathway of Jurkat cells.