Synthesis, Molecular Docking and Cytotoxic Activity Evaluation of Organometallic Thiolated Gold(I) Complexes

Document Type: Research article

Authors

1 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

3 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

4 Department of Medicinal Chemistry, School of Pharmacy Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

The complex [(PhCH2NC)AuCl], 1, was prepared by the reaction of [(Me2S)AuCl], A, with an equimolar amount of benzyl isocyanide (PhCH2NC) ligand. Through a salt metathesis reaction, the chloride ligand in 1 was replaced by potassium benzothiazole-2-thiolate (Kbt) and potassium benzoimidazole-2-thiolate (Kbi) to afford complexes (PhCH2NC)Au(κ1-S-bt)], 2a and (PhCH2NC)Au(κ1-S-bi)], 2b, respectively, which were characterized by NMR spectroscopy. The cytotoxic activities of 2a and 2b were evaluated against three human cancer cell lines, including A549 (lung), SKOV3 (ovary), and MCF-7 (breast). Our results indicated that 2a exhibited comparable cytotoxicity on investigated cell lines with cisplatin. It showed a good anti-proliferative activity with IC50 of 19.46, 11.76 and 13.27 μM against A549, SKOV3 and MCF-7 cell lines, respectively. The effects of these complexes on the proliferation of the non-tumorigenic epithelial breast cell line (MCF-10A) showed their good selectivity between the tumorigenic and non-tumorigenic cell lines. Molecular docking simulation studies were also conducted to determine the specific binding site and binding mode of the synthesized gold complexes to DNA and thioredoxinreductase (TrxR) as their proposed targets.                                                                                                                                                

Graphical Abstract

Synthesis, Molecular Docking and Cytotoxic Activity Evaluation of Organometallic Thiolated Gold(I) Complexes

Keywords