New Imidazo[4,5‐c]pyridine‐piperidine Hybrids as Potential Anti‐cancer Agents and In‐Silico Studies

Abstract

AbstractDesign and synthesis of a series of novel hybrid molecules that combine Imidazo[4,5‐c] pyridines with piperdines are presented in this paper. Total 17 derivatives were meticulously synthesized and characterized using 1H NMR, 13C NMR, MS and elemental analysis techniques. The in vitroanticancer activities are estimated by verifying their effectiveness against the MCF‐7 human breast adenocarcinoma and A549 lung cancer cell line, with cisplatin and doxorubicin serving as reference drugs. Several of these compounds demonstrated significant potential, displaying IC50 values within the range of 12.26–84.5 μM for A549, and 13.37–69.82 μM for MCF‐7. Notably, compound 11 bis found to be more potent than the standard drug cisplatin with an IC50 of 12.26±0.8 μM against A549 cells, while compound 11 d exhibited highest inhibition with an IC50 of 13.37±0.4 μM against MCF‐7 cells. Although its effectiveness was moderately lower when compared to doxorubicin, it still retained substantial anticancer activity. Molecular docking studies were performed to decouple the binding affinity and ligand interactions of the compounds with the estrogen receptor alpha (ERα) (PDB ID: 3ERT). The pharmacokinetic evaluation revealed favourable drug‐likeness properties for all the molecules, suggesting their potential as therapeutic agents.