Design, Synthesis and In‐Silico Studies of Piperidine‐Dihydropyridine Hybrids as Anticancer Agents

Abstract

AbstractIn this study, we designed, synthesized and characterized a novel series of piperidine‐dihydropyridine hybrid compounds and characterized them by 1H‐NMR, 13C NMR, mass spectrometry (MS), and elemental analysis. Subsequently, we assessed their in vitro anticancer potentials against the human breast adenocarcinoma cell line MCF‐7 and the lung cancer cell line A‐549. Several of these compounds demonstrated significant activity, with IC50 values ranging from 15.94 μM to 48.04 μM for A‐549 and 24.68 μM to 59.12 μM for MCF‐7, when compared to the reference drug Cisplatin.Notably, a compound featuring a 3‐fluoro substitution in the carboxamide series exhibited robust inhibitory effects, with an IC50 of 15.94±0.201 μM against A‐549 cells and an IC50 of 22.12±0.213 μM against MCF‐7 cells, respectively. Additionally, a compound containing a cyclobutyl ring displayed potent activity, with an IC50 of 16.56±0.125 μM against A‐549 and an IC50 of 24.68±0.217 μM against MCF‐7 cells, respectively. Furthermore, molecular docking studies against the Epidermal Growth Factor Receptor (EGFR) (PDB ID: 2J6M) revealed favourable binding scores and interactions, suggesting their potential as promising candidates for further investigation in the context of anticancer drug development.