Cytotoxic activity evaluation, DNA and thioredoxin reductase enzyme interaction studies of heterobimetallic Pt(II)-Au(I) complexes as potential anticancer agents

Platinum-based chemotherapy drugs like cisplatin are widely used in the treatment of cancer. However, because of its high side effects, the use of these compounds is limited. All of today's efforts is to design new platinum drugs, as well as hybrid of gold and platinum, which have a similar profile with cisplatin but have less side effects and wide spectrum on different cancer types. In this study, the cytotoxic activity of heterobimetallic Pt(II)-Au(I) complexes on the cancer cell lines such as cervix (Hela), colon (SW1116), breast (MDA-MB-231) as well as normal breast (MCF-12A) cell line was evaluated using MTT method. Molecular docking studies of these compounds with DNA and thioredoxin reductase (TrxR), as targets for platinum and gold compounds, were conducted using AutoDock 4.2 software. Using the comet assay, genotoxicity of the best cytotoxic compound was also evaluated. In evaluating the cytotoxic activity, 1b and 2b complexes exhibited greater cytotoxicity than cisplatin. All compounds exhibited lower toxicity than cisplatin on normal breast cell line (MCF-12A). The interaction of complexes with DNA and TrxR using molecular docking was also investigated and their binding mode and binding site were determined. The genotoxicity effect of these compounds was also confirmed by the comet assay. These complexes with further biological studies, have the ability to play a more effective role in the treatment of cancer.