非对称双(均三唑席夫碱)衍生物的合成及抗肿瘤活性

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

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L12103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20.0μmol·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.

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-Se, namely 2-（p-methoxyphenyl）-1- salicylideneamino-5- { 3-phenyl- 3- [N-（2-（2-dimethylaminoethylthio）-s-triazol- l-yl）imino]propylthio}-s-triazoles, respectively. The structures of new compounds synthesized were characterized by elemental analysis and spectral data, and their in vitro antitumor activity was also assayed against three cancer cells of CHO, HL60 and L1210 by an methylthiazoletrazolium （MTT） method. Among the fifteen novel compounds synthesized, bis（Schiff base）s 5a-5e showed the most potent cytotoxicity with the IC50 below 20.0μmol·L^-1, especially 5c beating two （2-methoxyphenyl triazole） rings was comparable to bisantrene.