1,3,4-噻二唑三氮烯化合物的合成和生物活性研究  

Synthesis and Biological Activities of 1,3,4-Thiadiazole Triazene Compound

作　　者：张明千 刘斌凯 雷强[1] 颜景东 赵中玉 龙跃[1] Zhang Mingqian;Liu Binkai;Lei Qiang;Yan Jingdong;Zhao Zhongyu;Long Yue(College of Chemistry and Molecular Engineering,Zhengzhou University,Zhengzhou 450001)

机构地区：[1]郑州大学化学与分子工程学院

出　　处：《有机化学》2019年第4期1064-1069,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.J1210060);河南省科技攻关计划(No.0624420031);河南省基础研究基金(No.022463001)资助项目~~

摘　　要：利用拼接原理将药效基团三氮烯与l,3,4-噻二唑相拼接,合成了15个未见报道的1,3,4-噻二唑三氮烯类衍生物,并用核磁共振波谱(NMR)、红外光谱(IR)和高分辨质谱(HRMS)等方法确定化合物结构.通过以典型三氮烯药物达卡巴嗪(DTIC)和药物5-氟尿嘧啶(5-FU)作参照,对人食管癌细胞(EC109)、人胃癌细胞(MGC803)和人前列腺癌细胞(PC-3)做活性检测,结果显示部分化合物对人胃癌细胞(MGC803)的抑制作用强于达卡巴嗪(DTIC),其中2-(3-甲基苯胺基)-5-[4-(3,3-二甲基三氮烯-1-基)苯基]-1,3,4-噻二唑(8c),2-(2-甲氧基苯胺基)-5-[4-(3,3-二甲基三氮烯-1-基)苯基]-1,3,4-噻二唑(8f),2-(3,4-二氯苯胺基)-5-[4-(3,3-二甲基三氮烯-1-基)苯基]-1,3,4-噻二唑(81)的IC50值低于5-氟尿嘧啶,分别为5.3,6.5和6.3 μmol/L;部分化合物对人前列腺癌细胞(PC-3)的抑制作用强于达卡巴嗪(DTIC),其中81的IC50值低于5-氟尿嘧啶,为13.5μmol/L.Using the splicing principle of combining the pharmacological group triazene with 1,3,4-thiadiazole,15 unreported 1,3,4-thiadiazole triazene derivatives were synthesized.The structures of the compounds were determined by nucleated magnetic resonance spectroscopy(NMR),infrared spectroscopy(IR)and high-resolution mass spectrometry(HRMS).By using the typical triazene drug dacarbazine(DTIC)and drug 5-fluorouracil(5-FU)as a reference,the activity detections of human esop-hageal cancer cells(EC109),human gastric cancer cells(MGC803),and human prostate cancer cells(PC-3)were carried out.The results showed that some compounds inhibited human gastric cancer cells(MGC803)more strongly than dacarbazine(DTIC),and the IC50 values of compounds 2-(3-methyanilino)-5-[4-(3,3-dimethyltriazol-1-yl)phenyl]-1,3,4-thiadiazole(8c),2-(2-methoxyanilino)-5-[4-(3,3-dimethyltriazol-1-yl)phenyl]-1,3,4-thiadiazole(8f),and 2-(3,4-dichloroanilino)-5-[4-(3,3-di-methyltriazol-1-yl)phenyl]-1,3,4-thiadiazole(8l)were lower than those of 5-fluorouracil with 5.3,6.5 and 6.3μmol/L,respec-tively.Some compounds inhibited human prostate cancer cells(PC-3)more strongly than dacarbazine(DTIC),and the IC50 value of 8l is lower than that of 5-fluorouracil with 13.5μmol/L.

关 键 词：三氮烯 1 3 4-噻二唑 人食管癌细胞 人胃癌细胞 人前列腺癌细胞 

分 类 号：O626[理学—有机化学]