Ionic liquid mediated synthesis and in vitro mechanistic exploration of polycyclic cage‐like heterocyclic hybrid

Abstract

AbstractA 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., α,β‐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.