Molecular docking and in vitro anticancer studies of silver(I)-N-heterocyclic carbene complexes.

A series of symmetric and unsymmetrical benzimidazolium-based N-heterocyclic carbene (NHC) precursors (1a-i) and their silver complexes (2a-i) have been synthesized. The Ag(I)-NHC complexes were characterized by 1H, 13C{1H} NMR, FTIR, LC/MS-QTOF, and elemental analysis. Anticancer and cytotoxic activity of all Ag(I)-NHC complexes were tested against healthy fibroblast cell line (L929), breast cancer cell line (MCF-7), and neuroblastoma cell line (SH-SY5Y) by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium] assay. The 2b, 2c, 2e, 2g, 2h, and 2i complexes showed higher cytotoxicity than cisplatin against SH-SY5Y and MCF-7 and lower cytotoxic activity against L929 cell lines. Because of their high cytotoxic activity against cancer cells and low cytotoxicity against healthy fibroblast cell lines, the 2b, 2c, 2e, 2g, 2h, and 2i are expected to be new lead compounds. In addition, molecular docking studies were performed to explore the binding interactions of silver complexes with the enzyme to explore new anticancer compounds. Furthermore, ADME properties of all complexes were predicted to explore lead-like characteristics and may be a potential drug candidate for cancer treatment.

Synthesis and investigation of antiproliferative activity of Ru-NHC complexes against C6 and HeLa cancer cells.

The 2-methylpyridine, 2-diethylaminoethyl, and isopentyl linked a series of symmetric and unsymmetric benzimidazolium salts 2a-e were prepared and used in the synthesis of silver-N-heterocyclic carbene (NHC) complexes (3a-e). The Ru(II)-NHC complexes (4a-h) were synthesized via transmetalation reaction from 3a-e. 4a-h complexes were converted to Ru(II)-NHC.HCl complexes (5ah) by HCl solution of diethyl ether and characterized by different spectroscopic techniques such as 1H and 13C NMR, LC/MS-Q-TOF, FT-IR, elemental analysis, and melting point detection. We examined the effect of the structural difference of complexes on anticancer activity via different arenes and metal centers. Antiproliferative activity of 5a-h and 3a was tested against human cervix adenocarcinoma (HeLa) and rat glioblastoma (C6) cell lines by ELISA assay. The IC50 value of 5b, 5c and 5e complexes exhibited good cytotoxic activity than cisplatin on C6 (14.2 ± 0.5 mM; 16.2 ± 0.4 mM; 24.2 ± 0.7 mM, respectively) and HeLa (11.1 ± 0.5 mM; 13.7 ± 0.3 mM; 22.8 ± 0.8 mM, respectively) cell lines.