Novel hexacyclic cage-like hybrid heterocycles have been synthesized in excellent yields employing a relatively less explored non-stabilized azomethine ylides derived from acenaphthenequinone and tyrosine with functionalized dipolarophiles using [3 + 2] cycloaddition strategy. The synthesized hexacyclic cage-like hybrid heterocycles were characterized by spectroscopic analysis. Following the physical characterization, these cage-like hybrid heterocycles were tested for their biological activity by means of different cancer (A549 and Jurkat cells) and non-cancer (BRL-3A and PCS-130) in vitro cell culture systems. The results of the study under tested concentrations (up to 100 μM) indicated that these compounds are not affecting any viability to the cell growth of non-cancer cells, while providing significant anticancer activity against both of the cancer cells. Further analysis of in-depth mechanistic study for the cell death indicated that these compounds are exhibiting late apoptosis or early necrosis pathway to the cells where it is operated by the induction of caspases.
Keywords: [3 + 2] cycloaddition; anticancer activity; apoptotic mechanism; hexacyclic cage-like hybrid heterocycles; in vitro toxicity; role of caspases.