Studies On Antitumor Activity And Toxicity Of Novel Ruthenium (?)Complexes

Since cisplatin has been be applied to in clinic as an antineoplasticdrug and been effective successfully,the scientists from all over the worldbegan to commit to a research on the anticancer activity of metalcomplexes,and hope to develop a new antitumor drug,thus not onlyreducing the normal side effects of drug to the human body,butpreventing the growth and reproduction of tumor cell more efficiently.Through a large scale systematic research from the National CancerInstitute(NCI),the scientists picked up 10 kinds of metal(including tensof thousands of kinds of metal complexes)from 55.The complexes theyformed reveal obvious anti-tumor activity,and ruthenium complexes areregarded as one of the most promising anticancer chemotherapy drugs.After these compounds getting into the organism,compared with thenormal tissue,a great number of compounds has been absorbed by thetumor tissue,thereby reflecting its low toxicity.At the same time,thebiological activity of ruthenium complexes has also make it become thefocus of research scientists.1.This thesis is based on the previous successfully synthesized andappraised ruthenium(?)complexes:[Ru(phen)2GFLX]Cl2,discussingthe interaction of this complex and DNA,its impact on the proliferationof tumor cells outside human body,as well as the influence of acutetoxicity in mice,and establish S180 tumor-burdened mouse model,thenconduct a test on the efficacy of a drug inside mouse.The main tasks andresults are as follows:Studying the interaction type of[Ru(phen)2GFLX]Cl2 and ct-DNA by Spectroscopy(electronic absorptionspectrum,fluorescence spectrum),the data shows that the Electronicabsorption peak of[Ru(phen)2GFLX]Cl2 present a hypochromiceffect andthe intensity of the fluorescence spectrum becomes more heavy as addingthe ct-DNA.From these results,there is a preliminary judgment that[Ru(phen)2GFLX]Cl2 combine with ct-DNA in the way of insertingmutually.2.Using MTT to study the impact of[Ru(phen)2GFLX]Cl2 onproliferation of human breast cancer cell(MCF-7),human liver cancercells(Hep-G2),human gastric cancer cells(SGC-7901),human coloncancer cells(HCT-116)and human cervical cancer cells(Hela).Theresults show that when the concentration of complexes is 1 X 10-4 mol/Land the action time is 72 hours,their growth rate is respectively 34.3%,37.8%,12.3%,37.8%and 35.23%.It is Indicated that the complexeshave different inhibitory effect on these five kinds of cells,and theinhibition effect is SGC-7901>HCT-116>MCF-7>Hela>Hep-G2.3.In the way of the tail vein injection to study the acute toxicity of[Ru(phen)2GFLX]Cl2 in mice.Experimental results show that thecomplexes have certain toxicity in mice.M Median lethal dose LD50 asfollows:2.99 mg/kg;Complexes decrease the number of white bloodcells(P = 0.031)in the blood of mice and the effect on viscera mainlyembodies in the renal toxicity.4.This thesis establishs the S180 tumor-burdened mouse model,and preliminary study the[Ru(phen)2GFLX]Cl2 inhibition for the growthof S180 sarcoma.When the intraperitoneal injection of drug dose is 1.50mg/kg,the inhibition rate of this complexes in mice is 32.3%,and it hasan effect on the immune organs of mice.