Synthesis, Characterization And Study On Antitumor Activites Of New Type Platinum(Ⅱ) Complexes

Today, cisplatin and carboplatin are widely utilized antitumor drugs in the world. Morever cisplatin is one of the three most widely utilized antitumor drugs in the world and has annual sales of approximately $500 million (U.S.). They are highly effective in treating testicular cancer, ovarian cancer and head and neck cancers. Despite its success, cisplatin has several disadvantages that include (1) severe toxicity such as nephrotoxicity and neurotoxicity; (2) relatively narrow range of tumors (3) a high level of cross-resistance between cisplatin and carboplatin. To circumvent these limitations, the search continues for an improved platinum antitumor agent, motivated by the desire to design a less toxic,high active, orally active compound that is non-cross-resistant with carboplatin and cisplatin. We have already done some work as follows.In chapter 1, we have already summaried current situation of platinum antitumor agents, synthetic methods of mixed ammine/amine platinum complexes, the structure-activity relationships of mixed ammine/amine platinum anticancer agents and anticancer mechanism of cisplatin.In chapter 2, platinum complexes of ammine/amine with carboxylate are quite promising against some cancers according to the literatures. At the same time, we have already synthesized thirteen precursor complexes of platinum and eighteen platinum complexes for the first time. They have been characterized by elemental analyses, molar conductance, infrared, ~1H nuclear magnetic resonance, TG-DTA and so on.In chapter 3. we have already detected anticancer activity of thirty-one platinum complexes in vitro by using MTT and SRB methods. The results indicated that four platinum complexes had anticancer activity against some human cancer cell lines, seven platinum complexes had activity against EJ under the assay conditions.In chapter 4, we have already studied the influence of six representing platinum complexes on cell proliferation by using MTT and SRB methods. The results indicated that complex 12 inhibited the proliferation of HL-60,BGC-823, EJ, MCF-7 and HCT-8. Morever it had a stronger inbibitory effect than cisplatin or same inhibitory effect as cisplatin, complexes 28 and 31 had same inhibitory effects as cisplatin on HL-60, but they had weaker inhibitory effects than cisplatin on BGC-823 and EJ, complexes 22, 25 and...