Au (Ⅲ) Complexes Anti-cancer Mechanism Research

From the mid-twentieth century, the gold-containing drugs have already been used forthe treatment of rheumatoid arthritis. A large number of Au(I) and Au(III) complexeswere successfully synthesized, among which the most famous for Au (I) classisAuranofin. These drugs are mainly used for the treatment of active rheumatoidarthritis. They can delay the rheumatoid arthritis lesions, improve symptoms, andhave good tolerance. Au(III) and Pt(II) have identical4f145d86d0closed-shell electronconfiguration, and their coordination modes take the same square planar configuration.Inasmuch as the Ptanti-cancer drugs produce a series of side effects, a large number ofAu(III) class of gold complexes are synthesized as anew potential anti-cancer drugs.And their cytotoxicity has become a recent research focus.Au(III) complexes as potential anti-cancer drugs how amore variable chemicalconfiguration. The configurations of interest reported in the literature may besummarized into four categories:(i) the single ligand;(ii) coordinated by porphyrin;(iii) coordinated by a variety of organic molecules;(iv)coordinated by bi-dentateligands. A wide variety of Au(III) complexes are reported in the literature, but most ofthem focused on the structural characterization and in vitro experiments. In the few invivo experiments, the choice of tumor cell lines and experimental conditions aredifferent, leading to the compounds’ anti-cancer activity do not show regularity andcomparability.So far the anticancer mechanism of the Au(III) complexes are still in controversy,which includes the following aspects：(i) The structure-activity mechanisms, includingthe impact of taking off groups and the influence of ligands. Easily losing ligands andaromatic conjugate groups of Au(III) complexes have a strong cytotoxicity.(ii) thesulfur-containing organic bio-molecular interactions. Sulfhydryl groups and thereactivity of Au(III) complexes can limit the progression of the cancer cell growth, ofwhich the biological targets may be the thiol-sulfur atom.(iii) the interaction betweenproteins and their protease. The center of Au(III) complex may have a strongcoordination with histidine.(iv) the interaction of the DNA fragments. For Au(III) hasthe identical electronic configuration with Pt(II), Au(III) complexes may also beassociated with DNA fragments cross-linking or chain with in the chain cross-linking. And they have Au(III) complexes on the mitochondrial gene regulatoryfunctional and the cell membrane destructive effects “hemolysis”.Three aminoquinoline Au(III)complexes and its derivatives are selected as aresearch object. We used the density functional theory and other quantum chemicaltheoretical methods to investigate the anti-cancer activity and the anticancermechanism of aminoquinoline Au(III)complexes and its derivatives. Upon reasonableselection of DNA fragments as the attack target of Au(III) complexes, a series ofsystematic theoretical calculations using density functional theory have been carriedout on the selected system to obtain a reasonable calculation results. Compared withsome experimental results, we aimed at finding a feasible anti-cancer mechanism forthe Au(III) complexes. Through our research work, we find that the DNA fragmentcan be replaced by the Au(III) complexes center. The barriers of the hydrolysis step ofthe Au(III) complexes is consistent with its anti-cancer activity. The present workshould provide preliminary guidance on discovery of working mechanisms of theanticancer drugs with gold complexes.