Study On Synthesis Of 7-ethyl-10-hydroxycampthothecin And Synthesis And Cytotoxicity In Vitro Of Its New Derivatives

7-ethyl-10-hydroxycampthothecin (SN-38) is the intermediate which is used to synthesize Irinotecan(anticancer drug). The price of SN-38 is 15 times more than campthothecin(CPT). To get the safe, easy, cheap synthsis route of SN-38, the synthesis route of 7-ethyl-10-hydroxycampthothecin was investigated in detail. Based on the structure of SN-38, sixteen new derivatives of campthothecin were prepared, and their structures were characterized by ~1HNMR, IR, MS.In this paper, SN-38 was first prepared by CPT through three step reaction.To get the high yield of 7-ethyl-camptothecin, different reaction conditions were investigated, and we got the optimum reaction condition. In this condition, the finally yield of 7-ethyl-camptothecin was 42.20ï¼…respectively. This technology can be used in industry.Sixteen SN-38 derivatives were designed and synthesized by nuclephilic displacement. Compounds 7-16 are quaternary salt derivatives of SN-38. They have high yields and good water solubility, which resolved the poor water-solubility of camptothecins. Compounds 17-20 are no-salt derivatives of SN-38, which showed better cytotoxic activity in vitro.The cytotoxicities of these derivatives were measured on three different human cancer cell lines (MCF-7, A549 and PC-3) using MTT assay in vitro. Yopotecan and CPT were used as reference compounds. Compared with the strong cytotoxicity on all cancer cells, most of the derivatives showed less cytotoxic activity in vitro. The camptothecin derivatives 17 and 18 showed similar eytotoxic activity to topotecan on cell MCF-7 and PC-3. The salt derivatives 7-16 showed less cytotoxic activity than the no-salt derivatives 17-20. So the water solubitity of derivatives have important effect on cytotoxicity of derivatives.