Synthesis and Characterization of Novel Imidazole Derivatives and Their Metal Complexes Cu(II) and Pd(II) as Breast Anticancer: In Vitro Approach Coupled with DFT, Molecular Dynamics, and Molecular Docking Studies

Abstract

Breast cancer remains a significant and prevalent health challenge impacting millions of people globally. In this current study, a new imidazole ligand has been synthesized from the reaction of (E)-2-(4-chlorophenyl)-4-(4nitrobenzylidene) oxazol-5(4H)-one with thiosemicarbazide. This ligand was determined by techniques for elemental analysis and NMR spectral characterization. The synthesized complexes (copper S1 and palladium S2) were characterized, and their shapes were determined through the employment of elemental analysis, spectral characterization, magnetic measurements (Bohr Magneton, B.M), and conductivity assessments. The electronic spectra and magnetic moment information indicate that the complexes exhibit a square planar structural arrangement. This work involves screening the ligand and its complexes in vitro using cytotoxicity and in silico using DFT, molecular docking, and molecular dynamics. These complexes were examined in MCF-7 cells, which have anti-breast cancer properties. The results exhibit that S2 has the highest cytotoxicity effect, with more than 50 % after 24 h and higher than 75 % within 72 h. According to the findings of the quantum calculations, the complexes' chemical structure showed a strong biological reactivity, with S2 showing the highest reactivity. The attachment of progesterone and estrogen hormones to these receptors promotes the growth of cancer cells. Therefore, we chose two target receptors for these hormones (4OAR and 3ERT) that have been demonstrated to be trustworthy in studies reported in the literature. The results of molecular docking showed that S2 has a higher binding potency with both proteins, -183 against 3ERT and -202 against 4OAR, respectively, followed by S1. Results of molecular dynamics simulations, which were then applied to further investigate the interaction of the ligand with the binding site of the proteins, indicated that the estrogen receptor would likely be the compound's major target.