Microwave-Assisted Synthesis of 4-Aryl-1,4-dihydropyridines as Potent Anticancer Agent and Their In-Silico Studies

In our effort directed toward the discovery of novel potent anticancer agents, a large library of novel 4-aryl-1,4-dihydropyridines (23-58) with heterocyclic ring at 4, position of aryl group has been synthesized through Hantzsch synthesis. These synthesized hybrids have been well characterized and evaluated for their cytotoxic activities against a panel of human cancer cell lines viz. EAC, HEK, and MCF cell lines by MTT assay. The cytotoxic activity has been revealed by the effects of various types of substituent present on the dihydropyridine ring. All the synthetics (23-58) have shown good potency against EAC cell line. However, compounds 36, 40, 42, and 54 have displayed significant inhibitory potential against both EAC and MCF-7 cell lines. In addition, these promising analogues have been selected for their molecular docking studies against 5TVQ protein to know the binding affinity which was identified to be a plausible target site. Compound 42 has exerted the highest inhibition effect on cancerous cells and more potency than the reference drug, doxorubicin even at low concentration (1 mu g/ml) and showed non-toxicity to human normal cells suggesting high safety to normal cells. Compound 42 has also shown the highest docking score and inhibition constant which could be regarded as convincing lead for further clinical pursuit.