Persuasive phytoestrogenic imidazole-based selenium N-heterocyclic carbenes: electronic, structural, and in silico anticancer potential investigations

The cellular antioxidant defense mechanism against reactive oxygen species (ROS) depends on selenium, a vital trace element. Numerous selenium-containing compounds have recently displayed a wide range of biological characteristics that make them intriguing scaffolds in medicinal chemistry. Among the several categories of phytoestrogens, Imidazole-Based Selenium N-heterocyclic carbene Compounds (IM-SeNHC) have drawn the most scientific attention. Several IM-SeNHC compounds were chosen for this theoretical study analysis. The goal of this study was to govern the binding capacity of each of the selected IM-SeNHC that have been identified as inhibitors of the proteins responsible for cancer EGFR, hTrkA, HER2, and cMet (PDB codes: 5GTY, 6PL2, 7JXH, and 3RHK, respectively). DFT and molecular docking investigations were carried out employing in silico software for their virtual screening. Conferring to the docking study, ligand 6 formed hydrogen bonds with protein 7JXH’s active pocket, followed by ligand 8 with protein 3RHK and 5GTY, and ligand 9 with protein 6PL2. Conferring to trends in polarizability and dipole moment, the energy difference values (0.299 eV and 0.277 eV) of IM-SeNHC compounds (3 and 8) show the rise in chemical potential, reactivity, and bioactivity brought on by the most stable structural configurations. Additionally, ADME was investigated to discover the pharmacokinetic characteristics of the targeted moieties. The cardiotoxicity analysis was performed, and confidence percentages accompanying these predictions vary across the dataset, ranging from around 57 to 99.9%, indicating differing levels of certainty in the predictions. This research showed that these ligands have a promising future in cancer therapy medications.