Synthesis, X-ray structure and cytotoxicity evaluation of carbene-based gold(I) complexes of selenones

Abstract

Abstract Gold(I)-carbene complexes containing a selenone ligand (L), [Au(IPr)(L)]PF6 {where, IPr = 1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene and L = N-i-propyl-1,3-imidazolidine-2-selenone, i-PrImSe (1), 1,3-diazinane-2-selenone, DiazSe (2), N-methyl-1,3-diazinane-2-selenone, MeDiazSe (3), 5-hydroxy-1,3-diazinane-2-selenone, HO-DiazSe (4) and 1,3-diazepane-2-selenone, DiapSe (5)} were synthesized using [Au(IPr)Cl] (0) and selenones. The complexes (1–5) were characterized by elemental analysis, IR and NMR (1H, 13C & 77Se) spectroscopy. The crystal structure of complex 1 was determined by single crystal X-ray diffraction technique and the analysis reveals that the complex exhibits a distorted linear geometry around gold(I) atom. In vitro cytotoxic assays of the complexes were performed on three human cancer cell lines; HCT15 (colon cancer), A549 (lung cancer) and MCF7 (breast adenocarcinoma). Complexes 1 and 3 exhibited greater activities against HCT15 cells compared to the other complexes (2, 4 and 5). All complexes exhibited moderate to high IC50 values (less active) against A549 and MCF7 cell lines with respect to cisplatin. Molecular docking studies showed the potential inhibitory capacity of the gold complexes towards DNA topoisomerase 1 with complex 1 having the highest binding affinity with a score of −38.68. The distance between the gold atom in the complex and the oxygen atom of the carbonyl group of thymine was measured for all complexes. Complex 4 had the shortest bond distance of 3.64 A, while complex 5 had the longest one of 6.89 A.