摘要/Abstract

利用拼接原理将药效基团三氮烯与1，3，4-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（8l）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8l的IC₅₀值低于5-氟尿嘧啶，为13.5 μmol/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
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 6.3 μmol/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 13.5 μmol/L.
Key words: triazene, 1,3,4-thiadiazole, human esophageal cancer cells, human gastric cancer cells, human prostate cancer cells


PDF全文下载地址:

点我下载PDF