Although certain substituted cis-stilbenes have displayed potent tubulin polymerization inhibitory activity and significant cytotoxicities in cancer cell cultures, these compounds have limited aqueous solubility and are therefore difficult to formulate for in vivo evaluation. A series of water-soluble N-(3,4,5-trimethoxybenzyl)aniline salts has therefore been synthesized in which the olefinic bridge of the stilbenes is replaced by an aminomethylene hydrochloride moiety. A relationship was found between the size of the substituent in the 4-position of the aniline ring and both antitubulin activity and cytotoxicity, such that the smaller the substituent, the greater the potency. The most promising of the newly synthesized compounds was 4-methyl-N-(3,4,5-trimethoxybenzyl)aniline hydrochloride, with an IC50 value of 3.5 microM for inhibition of tubulin polymerization and cytotoxicity for a wide variety of cancer cell lines. The cytotoxicities of the benzylaniline hydrochlorides correlated remarkably well with their antitubulin activities.

中文翻译：

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一系列苄基苯胺盐酸盐的合成和评估，它们通过抑制微管蛋白的聚合作用发挥潜在的细胞毒性和抗有丝分裂剂的作用。

尽管某些取代的顺式-苯乙烯衍生物在癌细胞培养中显示出有效的微管蛋白聚合抑制活性和显着的细胞毒性，但这些化合物的水溶性有限，因此难以配制用于体内评估。因此，已经合成了一系列水溶性的N-（3,4,5-三甲氧基苄基）苯胺盐，其中斯蒂芬苯的烯烃桥被氨基亚甲基盐酸盐部分取代。发现在苯胺环的4-位上的取代基的大小与抗微管蛋白活性和细胞毒性两者之间存在关系，使得取代基越小，效力越大。新合成的化合物中最有希望的化合物是4-甲基-N-（3,4,5-三甲氧基苄基）苯胺盐酸盐，IC50值为3。5 microM用于抑制各种癌细胞系的微管蛋白聚合和细胞毒性。苄基苯胺盐酸盐的细胞毒性与其抗微管蛋白活性显着相关。