Synthesis, DFT and molecular docking studies of N-Heterocyclic carbene selenium compounds conferring anticancer and antibacterial activity

Target based drug design is an important strategy that increases the selectivity, efficacy and safety of drug candidates. In this study we designed synthesis of benz-imidazolium salts (L1-L3) and selenium compounds (C1–C3) to investigate their enzyme inhibition potential and bioactivity. Successful synthesis was confirmed through analytical techniques like UV–Vis., FTIR, ¹H & ¹³C NMR and mass spectrometry that further supported by computational (DFT) studies. Molecular docking studies of C1–C3 against key molecular targets (COX-1, EGF, VEGF and HIF) was conducted. Among the test compounds C1 showed an impressive binding affinity of −6.14 kcal mol⁻¹ against EGF which is comparable to standard drug 5-FU (−4.97 kcal mol⁻¹). The validation of docking results through in vitro studies confirmed C1 as most potent inhibitor among the test compounds, having inhibition of 67.4 ± 1.3 % and 86.7 ± 1.8 % against COX-1 and EGF respectively. Furthermore, test compounds showed significant inhibition potential against thioredoxin reductase (TrxR). Cytotoxicity profiling across HepG2, HeLa and A-2780 cell lines confirmed C1 as the lead compound, with IC₅₀ values of 0.956, 1.986, and 0.862 μg/mL, respectively. Test compounds also showed antibacterial activity by showing inhibition zone 8.5 ± 1.1–27.0 ± 1.2 mm against E. coli and S. aureus. These findings showed that NHC based selenium compounds could be a potential drug candidate for chemotherapy against multiple cancerous strains.