Synthesis of selenium- N -heterocyclic carbene adducts with antiproliferative activity against human lung cancer cells: experimental and computational investigations

Three new mononuclear selenium adducts (MC1–MC3) and their corresponding N-heterocyclic carbene (NHC) salts (ML1–ML3) derived from benzimidazole were synthesized and characterized to evaluate their anticancer potential. The benzimidazolium ligands were synthesized by the N-alkylation of 1-phenethyl-1H-benzimidazole and subsequently converted into selenium compounds using elemental selenium. 1H NMR,13C NMR, FTIR, and elemental analysis confirmed the structure of the prepared compounds. In parallel, the antiproliferative activities of the resulting compounds were assessed against A549, L929, and EA.hy926 cell lines using the MTT assay, with 5-fluorouracil (5-FU) serving as a reference compound. The study found that organoselenium compounds exhibited significant anticancer activity against A549 lung cancer cells, compared with the respective benzimidazolium salts, while demonstrating low toxicity toward normal cells. Among them, MC3 exhibited the highest cytotoxicity (IC50 = 1.75 ± 0.17 μM), even better than 5-FU (IC50 = 3.12 ± 0.18 μM). Furthermore, density functional theory studies indicate that selenium adducts show low highest occupied molecular orbital–lowest unoccupied molecular orbital gaps and more electronic reactivity as compared to ligands. Additionally, molecular docking of selenium compounds against HIF revealed that MC3 displays high binding affinity (−6.4 kcal mol−1), which is consistent with the observed experimental trends. These results highlight the potential of selenium-containing NHC compounds as versatile anticancer agents in medicinal chemistry.