Synthesis Of Dithiocarbamate Metal Palladium, Platinum, Rhodium Complexes And Their Antitumor Activity

Cancer is a common and frequently encountered disease,which is serious threat to human life.Its mortality rate is second only to cardiovascular disease,which is considered one of another major cause of human death.Since the platinum metal complexes can be seen as anticancer drugs,many other kinds of metal complexes have been found to have antitumor activity,such as Au??,??,Fe???,Pt???,Ru??,??and V???etc.But there are still very few other metals to be approved,which explains the shortcomings of our existing research system.In order to seek novel high active lead structure,the bioactive unit dithiocarbamate were introduced into the platinum,palladium and ruthenium complexes with good anti tumor activity using by the bioisosterism and the connecting principle of actively biological groups in this paper.Twenty-four new platinum???,palladium???,ruthenium???-dithiocarbamate derivatives were designed and synthesized.The structures were characterized by ¹H NMR,¹³C NMR,31 PNMR,MS and X-ray diffraction.The anti-proliferative activity of these complexes was evaluated by MTT method.1?Based on the principle of connecting actively biological groups and biological arrangement,six heteronuclear iron???-platinum???-dithiocarbamate derivatives were successfully designed and synthesized.The antitumor activity of these complexes in vitro against four cancer cells was investigated.The preliminary results show that this kind of heteronuclear iron???-platinum???-dithiocarbamate derivatives against four tumor cells generally showed excellent antiproliferation activity.The structure and activity relationship showed that the cell activity was the best when the substituent was pyrrolidine,in which the level of activity against human hepatocellular carcinoma cell line was about 7 times higher than that of the control drug cisplatin.The complex substituted by methylpiperazine also showed higher cytotoxicity.These studies suggested that heteronuclear iron???-platinum???-dithiocarbamate derivatives showed excellent antiproliferative activity,whichwas a kind of excellent anti-tumor lead structure and was worth continuing in-depth study.2?Based on the principle of connecting actively biological groups and biological arrangement,six heteronuclear iron???-palladium???-dithiocarbamate derivatives were successfully designed and synthesized.The antitumor activity of these complexes in vitro against four cancer cells was investigated.The preliminary results show that some of heteronuclear iron???-platinum???-dithiocarbamate derivatives against HepG-2 cells showed good antiproliferation activity,which the IC50 values range from 3.0 to 17.30 ?M against HepG-2 cells.The level of the complex substituted by methylpiperazine was 3 times of the control drug cisplatin.However,compared with similar platinum complexes,the activity of palladium complexes was not significantly better than that of platinum complexes.At the same time,it also highlights this kind of complex need to be further optimized and improved.3?Based on the principle of connecting actively biological groups and biological arrangement,six kinds of p-cymene ruthenium???-dithiocarbamate derivatives and six kinds of cyclopentadienyl ruthenium???-dithiocarbamate derivatives were successfully designed and synthesized.The antitumor activity of these complexes in vitro against four cancer cells was also investigated.The preliminary results show that p-cymene ruthenium???complex substituted by methylpiperazine revealed excellent activity against Hep G-2 cells and its activity was better than that of cisplatin.However,cyclopentadienyl ruthenium???complexes only substituted by ethyl and pyrrole showed antiproliferative activity against SKOV-3 cells,and the other complexes had no obvious activity against four tumor cells.The overall activity is not as well as for p-cymene ruthenium???-dithiocarbamate derivatives.The structure and activity relationship showed that the individual p-cymene ruthenium???-dithiocarbamate derivatives were also a kind of good antitumor precursor structure and was worth continuing in-depth study.