Synthesis of N-heterocyclic carbene‑selenium complexes modulating apoptosis and autophagy in cancer cells: Probing the interactions with biomolecules and enzymes.

Growing cancer resistance is a global threat that calls for development of newer chemotherapeutic analogues especially targeted based therapy to enhance efficacy and selectivity. In this contribution, herein, we report synthesis of selenium incorporated N-heterocyclic carbene (NHC) compounds to explore their potential cytotoxicity against HeLa cells. Test compounds were assured for suitability as drug candidates through physiochemical properties that showed lipophilicity logP 0.85-1.45 for C1-C3 and found stable in biological media (DMEM), whereas, least reactive with N-acetyl cysteine (NAC) and L-glutathione. All the studied compounds showed good cytotoxicity against various cancer strains while compound C1 [3,3-(hexane-1,6-diyl)bis(1-phenethyl-1H-imidazole-2(3H)-selenone)] and C2 [3,3-(hexane-1,6-diyl)bis(1-decyl-1H-imidazole-2(3H)-selenone)] showed promising results with IC values of 14.65 ± 0.66 and 8.05 ± 0.35 μg/mL respectively as compared to positive control 21.5 ± 0.05 μg/mL against HeLa cell lines. These compounds showed six-fold higher apoptosis than control with higher accumulation of Ca ions intracellularly that alters the expression level of autophagy proteins and increased capase-9 activity. Cell cycle analysis indicated an arrest of cycle in G1 phase of HeLa cells when treated with C1 & C2. Test compounds showed prominent affinity for binding with DNA and inhibiting thioredoxin reductase enzymes in time dependent manners. These findings indicate that Selenium NHC compounds are promising drug candidates to induce cytotoxicity via apoptosis, autophagy and mitochondrial membrane disruptions to manage tumor growth.