Synthesis, Breast Cancer Activity, Molecular Docking and Dynamic Simulation of 1,4-Dihydropyridine Derivatives

Abstract

Breast cancer (BC) is the most prevalent cancer diagnosed in women, accounting for more than 1 in 10 new cancer diagnoses each year. Even though chemotherapy is successful in BC treatments, resistance to spreading these medications requires a new therapy. A new 1,4-dihydropyridine (ZL1-6) series was synthesized and characterized using spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR, and mass spectroscopy. The efficacy of these compounds against MFC7 breast cancer cells was assessed through a combination of in vitro, molecular docking, molecular dynamics, and MM-GBSA analyses. Notably, compound ZL4 exhibited promising activity against MFC7 cells (IC50 = 93.09 μg/ml), with a docking core of -6.728 kcal/mol and an MM-GBSA of -47.82 kcal/mol potentially involving the inhibition of EGFR as a mechanism of action. It is worth mentioning that these compounds were inactive against both E. Coli and S. Aureus wild strains. These findings provide a foundation for the development of innovative treatments for breast cancer.