Synthesis, characterization, and antitumor properties of Au(i)-thiourea complexes

The anticancer property of cisplatin has stimulated the development of metal complexes as antitumor agents. Among these complexes, metal thiourea complexes have attracted sufficient attention, and they possess the potential possibility to become new antitumor metallodrugs. Herein, four Au(i) complexes derived from N,N-disubstituted cyclic thiourea ligands were synthesized and characterized. The crystal structure analysis indicated that the complex Au(i)(3c)(2)OTf was a mononuclear crystal structure with Au(i) coordinated by two sulfur atoms. These Au(i) complexes exhibited excellent toxicities against several tumor cell lines, especially complex Au(i)(3c)(2)OTf (IC50 = 8.06 mu M against HeLa). It was found that Au(i)(3c)(2)OTf triggered a burst of ROS, disrupted the mitochondrial membrane potential (MMP), subsequently released Cyt-c, and then triggered the activation of caspase 9, caspase 7 and caspase 3. Mechanism experiments manifested that Au(i)(3c)(2)OTf induced the down-regulation of Bcl-2 and up-regulation of Bax, which further indicated that Au(i)(3c)(2)OTf triggered mitochondria-mediated apoptosis. In addition, the ROS scavenger-NAC completely blocked the apoptosis and inhibited the reduction of MMP, showing that Au(i)(3c)(2)OTf induced a ROS-dependent apoptosis pathway. These results indicate that Au(i)(3c)(2)OTf is worthy of in-depth research as an antitumor agent and may throw light on a better understanding of the effect of thiourea derivatives on antitumor mechanisms.