Ionic liquid mediated synthesis and in vitro mechanistic exploration of polycyclic cage-like heterocyclic hybrid |
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| Authors: | Raju Suresh Kumar Abdulrahman I Almansour Natarajan Arumugam D Kotresha J Carlos Menéndez Raju Ranjith Kumar |
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| Institution: | 1. Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia;2. Department of Studies in Botany, Davangere University, Davangere, India;3. Unidad de Química Orgánica y Farmacéutica, Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense, Madrid, Spain;4. Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, India |
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| 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., 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. |
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