Synthesis and computational insights of hybrid heterocyclic bis-chalcone compounds and their cytotoxic effects against breast cancer cells

Breast cancer is a common disease that employs chemotherapeutic drugs as a treatment approach. However, these drugs have several adverse effects, prompting the development of new drugs. Hence, this study aimed to synthesize a series of new heterocyclic bis-chalcone compounds using the Claisen-Schmidt reaction and evaluate their cytotoxicity in breast cancer Michigan Cancer Foundation-7 (MCF-7) cells. The selected compounds were then evaluated for molecular docking; molecular dynamics (MD) simulations; and absorption, distribution, metabolism, and excretion (ADME), pharmacokinetic, and drug-likeness property analyses. Among the synthesized heterocyclic bis-chalcone compounds, compounds 1d and 2d induced strong antiproliferative effects against MCF-7 cells with half-maximal inhibitory concentrations (IC50) of 32.51 ± 4.02 µM and 22.69 ± 6.95 µM, respectively. Molecular docking analysis showed that compound 2d had good binding affinity (-8.40 kcal/mol) when docked with the estrogen receptor alpha (ERα) receptor compared to compound 1d, which had a binding affinity of −8.10 kcal/mol. MD simulations revealed that these compounds were consistently stable throughout the 100 ns, with additional hydrogen-bond interactions. Moreover, the compounds satisfied the predicted ADME, pharmacokinetic, and drug-likeness requirements. This study demonstrated that compound 2d is a potent heterocyclic bis-chalcone compound with the potential to be used as an anti-breast cancer agent.