Synthesis and In Vitro Evaluation of Substituted Quinolines as New Apoptosis Inducers and Anticancer Agents: Pharmacophore-based Design

Abstract

Background: Cancer is a global health burden and the leading cause of death across the world after cardiovascular disease. Objective: The objective of this work was the design, synthesis, and pharmacological evaluation of 2-phenylquinolin-4-amine derivatives as apoptosis inducers and anticancer agents. Methods: In this study, we performed ligand-based pharmacophore modeling as a promising design strategy for the design of substituted quinoline derivatives as apoptosis inducers and anticancer agents. The designed compounds were synthesized as 2-phenylquinolin-4-amine derivatives and characterized by FT-IR, 1H-NMR, 13C-NMR, and Mass spectroscopy. Synthesized compounds were screened for apoptosis-inducing activity using caspase-3 activation and annexine-FITC assays, and also screened against cancer cell line (HT-29) in an antiproliferative assay. Results: Synthesized compounds 7a, and 7d demonstrated EC50 values of 6.06 and 6.69 μM in caspase-3 activation assay, respectively, and also showed late stage induction of apoptosis in annexine assay. Synthesized compounds 7a, 7d and 7i, also exhibited good antiproliferative activity with IC50 values of 8.12, 9.19, and 11.34 μM, respectively, which revealed that these are promising apoptosis inducers for the further development of new anticancer agents.