非对称双(均三唑席夫碱)衍生物的合成及抗肿瘤活性

为寻找新结构的水溶性抗癌先导化合物, 采用氨基均三唑硫代苯丙酮(1)与氨基均三唑硫醇(2a～2e)缩合得双均三唑单席夫碱化物3a～3e, 接着依次与氨基氯乙烷和水杨醛进行亲核取代和缩合反应, 分别得到含碱性侧链的单席夫碱4a～4e和非对称双席夫碱5a～5e. 所合成新化合物的结构经元素分析和光谱数据表征, 用甲基四噻唑蓝比色法(MTT)对新化合物进行了对于CHO, HL60和L1210 3种癌细胞株的体外活性试验. 在合成的15个新化合物中, 双席夫碱结构的抗癌活性最强, 其IC₅₀值在20.0 μmol•L^－1以下, 尤其是均三唑环连有双供电子取代基时(如化合物5c), 表现出潜在的活性, 其抗癌活性与上市药物比生群相当, 具有侯选药物研究的价值.

Synthesis and Antitumor Activity of Asymmetric Bis(s-triazole Schiff-base)s

To discover novel structurally soluble lead compounds for antitumor researches, 1-amino-2-(p-methoxyphenyl)-5-(2-benzoylethylthio)-s-triazole (1) was condensed with 1-amino-s-triazole-5-thiols (2a～2e) in the presence of concentrated H₂SO₄ to obtain bis-(s-triazole) Schiff-bases 3a～3e, which were subjected to a nucleophilic substitution with N,N-dimethyl-2-chloroethylamine to produce the corresponding bis-(s-triazole) Schiff-bases bearing a basic side chain 4a～4e. Condensation of compounds 4a～4e with salicylaldehyde afforded asymmetric bis-(s-triazole Schiff-base)s 5a～5e, namely 2-(p-methoxyphenyl)-1-salicylideneamino-5-{3-phenyl-3-[N-(2-(2-dimethylaminoethylthio)-s-triazol-1-yl)imino]propylthio}-s-tria-zoles, respectively. The structures of new com-pounds synthesized were characterized by elemental analysis and spectral data, and their in vitro an-titumor activity was also assayed against three cancer cells of CHO, HL60 and L1210 by an methylthiazole-trazolium (MTT) method. Among the fifteen novel compounds synthesized, bis(Schiff base)s 5a～5e showed the most potent cytotoxicity with the IC₅₀ below 20.0 μmol•L^－1, especially 5c bearing two (2-methoxyphenyl triazole) rings was comparable to bisantrene.