Studies Of Novel Anti-Tumor Indolin-2-one And Benzimidazole Compounds

Cancer remains a signigicant health concern in the world,and is the second leading cause of death after cardiovascular disease.In our courtry,the incidence of cancer increases every year.There is a lack of efficacious drugs for some solid-tumor therapy.In recent years,there has been a growing interest in the search for anti-tumor drugs with high efficacy,low toxicity and minimum side effects.Indol derivatives are recognized as a class of important heterocycles for their pharmacological properties.In partâ… of this dissertation,four new kinds of indolin-2-one derivatives were designed and synthesized,tested in antitumor activities in vitro and in vivo.Most compounds of the fourth series of derivatives showd more potent antitumor activity in vitro compared to the reference drug Sunitinib.Howevre, the compound selected from the fourth series of derivatives showed poor aqueous solubility and lower antitumor activities in vivo.Further improvements in terms of both potency and physical properties were made by introducing more hydrophilic substitutes,and test in inhibiting protein kinases were in further investigation.In partâ…¡of this dissertation,we designed and synthesized a novel kind of benzimidazole derivatives by introducing thiazole group in the 2-position of benzimidazole.The new derivatives,inserted different groups in the N1 position and thiazole ring,showed good antitumor activities against SMMC-7721 and A549 cell lines.Chimmitecan,a novel 9-substitrted derivative of camptothecin(CPT),is a potent inhibitor of topoisomerase I and displays outstanding activity in vitro and in vivo.In partâ…¢of this dissertation,we developed an efficient synthesis of chimmitecan.The main advantage of this procedure is that the product is much easier to purify and without the isomer byproduct.Our study has provited a new method of producing chimmitecan and its derivatives.