Theoretical Study On The Interaction Of Gold(Ⅲ) Antitumor Drug With Target Molecules

Among the nonplatinum antitumor drugs, which contains the NCSS segment of gold(III)-dithiocarbamato compounds have strong antiproliferative activity in vitro and in vivo and lower toxicity, especially to the kidney. Gold derivatives, for example, [Au(ESDT)Br2] and[Au(DMDT)Cl2] was found to be highly active against the androgen-resistant prostate cancer cell lines, in the research experiment of androgen resistance of prostate cancer, the researchers confirmed that the two gold compounds as potential drugs of therapies or cures for prostate cancer. On the basis of their good cytotoxicity observed in the early years in vitro, researchers mainly focused on the following problems: The behavior of these gold compounds under physiological conditions and how gold compounds works to the DNA and red blood cells, and prove that the possible biological target of these compounds. Recently, Some gold derivatives are widely reported stem form their mechanism is not clear. In this paper we research how gold derivatives behave, which containing segments of NCSS, and the direction of future development in gold anticancer drugs is discussed. Four possible anticancer drugs Au(DMDT)Br2, Au(DMDT)Cl2(DMDT=N, N- dimethyldithiocarbamate), Au(ESDT)Br2 and Au(ESDT)Cl2(ESDT= ethylsarcosinedithiocarbamate) as the research objects are selected by us.In the first two chapters, we mainly introduces the research background, the subject topics basis and theoretical calculation method, chapter three explores the theoretical study of substitution reaction of these compounds Au(DMDT)Br2, Au(ESDT)Br2 and Au(ESDT)Cl2 with cysteine and DNA purine bases. The fourth chapter shows the compound Au(DMDT)Cl2 interact with its target molecules in the bifunctional substitution reaction, which is based on the result of our previous monofunctional substitution reaction.The research result of chapter 3 indicates that the halogen ligands exert little influence on bromoaqua(chloroaqua) substitution reaction of several gold compounds with molecular targets.In general, cysteine as a target molecule is superior to the DNA purine bases. By comparing the two experiments of the gas phase optimizations and the aqueous solution optimizations, and the single point of same transition state in gas phase and aqueous solution, we can draw the conclusion that environment has a certain effect on the substitution reaction.Chapter 4 shows that the O site of cysteine and the N7 of adenine are weaker sites and the site of guanine(N7) is the strongest. In aqueous solution, the S site and N site(cysteine) as attack sites are neck and neck. There is charge transfer in the whloe substitution reactions.