O-Halogen-substituted arene linked selenium-N-heterocyclic carbene compounds induce significant cytotoxicity: Crystal structures and molecular docking studies

Abstract

Synthesis of N-arylated benzimidazolium salts 1–2, as stable N-heterocyclic Carbene (NHC) σ- donor ligands, was carried out by simple, facile and high yielding method. Respective Se-NHC compounds 3–4 were synthesized in water at 100 °C in open air environment using elemental selenium as reactant. Various spectroscopic methods (FT-IR, 1H and 13C NMR) were used for characterization of the products. Single crystal of salt 2 was analyzed by x-rays crystallographic analysis. In-vitro anticancer studies of the products 1–4 were carried out against breast cancer cell line (MDA-MB-231), cervical cancer cell line from Henrietta Lacks (HeLa), human normal endothelial cell line (EA.hy926) and adenocarcinoma cell line (A549) using MTT assay and compared with a standard drug 5-Flourouracil (5FU). The products 1–4 showed IC50 values less than standard drug 5FU against MDA-MB-231. Against HeLa cell line, compound 2 and its complex 4 were more potent with IC50 value of 0.05 µM and 0.082 µM, respectively as compared with 5FU having IC50 value of 4.9 µM. Against A549 cell line the products 1–2 showed good IC50 values while 3 was inactive with very high value of IC50 and 4 also showed good IC50 value of 19.02 µM. Against EA.hy926 cell line, both the salts 1–2 showed more toxicity with lower IC50 values than selenium counterpart 3–4. The docked conformation of VEGFA, EGF, COX1 and HIF with active conformation of selenium compounds 3–4 and 5FU revealed numerous potential interactions. The selenium adducts 3–4 were better with lower binding energies than 5FU, however, both showed almost same values of inhibition constants and binding energies against all proteins. Also, inhibition constants of compounds 3–4 were almost equal but less than 5FU.