Design,Synthesis And Antitumor Activity Evaluation In Vitro Of Novel Phenothiazine Derivatives

Phenothiazines are a class of important biologically active molecules,with good antipsychotic,antihistamine,anti-cancer,anti-bacterial,anti-tuberculosis and other biological activity,has a wide range of applications in clinical treatment;Triazole and aminodithioate structural units are widely found in many natural products,their good biological activity and potential pharmaceutical application value,which is one of the hotspots in the field of medicine research in recent years.Designed and synthesized two series of novel phenothiazine derivatives containing triazole or dithiocarbamate moiety on the basis of literature about the biological activity research on phenothiazine compounds and triazole or dithiocarbamate moiety.The anti-tumor activity of these compounds was evaluated in vitro.Specific research work in this thesis are as follows:1.Use knowledge of organic chemistry reactions,27 phenothiazine derivatives containing triazole moiety,21 phenothiazine derivatives containing dithiocarbamate moiety were synthesized.48 compounds were not reported in the literature.All of these new compounds were confirmed by 1H NMR,13 C NMR,HR-MS.2.MTT assay was used in MGC-803(gastric cancer),PC3(prostate cancer),EC-109(esophageal cancer)to investigate the anti-tumor activity of these synthetic compounds.The results showed that the IC50 of thiazolyl group-containing phenothiazine compounds 19 f,19i and 22 d were 7.88 ± 1.286?M,5.081 ± 0.809?M and 5.006 ± 1.046?M respectively in gastric cancer cells MGC-803,compounds 22 f,22j on the prostate cancer cell PC3 IC50 were: 6.762 ± 0.251?M,0.537 ± 0.316?M.In particular,the inhibitory activity of compound 22 j on prostate cancer cell PC3 is about 20 times that of 5-fluorouracil.Phenothiazine derivatives containing dithiocarbamate moiety 10g(IC50=8.59 ± 0.637 ?M)and 10p(IC50=8.71 ± 0.040 ?M)showed good antitumor activity against the measured tumor cells PC3 and was better than the positive control of 5-fluorouracil,and the activity of compound 10g(IC50 =7.96 ± 0.071?M)on tumor cell EC-109 was also superior to that of 5-fluorouracil.