氟喹诺酮C-3均三唑席夫碱硫乙酸的合成及抗肿瘤活性(X)

为进一步发现培氟沙星C-3羧基等排体-均三唑的结构优化新方法，用硫乙酸和席夫碱侧链作为其修饰基团，设计合成了12个新的C-3均三唑硫乙酸席夫碱目标化合物(7a~7l)，其结构经元素分析和光谱数据确证，评价了它们对SMMC-7721、L1210和HL60 3种肿瘤细胞株的体外抗增殖活性。初步药理筛选结果表明，目标化合物的抗肿瘤活性显著高于母体化合物1和前体胺6，尤其是苯环含氟原子和硝基的目标化合物(7j，7l)对SMMC-7721的IC₅₀已达到毫摩尔浓度。实验结果表明，氟喹诺酮C-3羧基的等排体均三唑杂环用席夫碱和硫乙酸这两种功能基侧链修饰有利于提高氟喹诺酮的抗肿瘤活性。

Synthesis and antitumor activity of fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives from pefloxacin(X)

To explore a new strategy for further optimization to the C-3 bioisteric heterocyclic ring of fluoroquinolones, twelve novel fluoroquinolone C-3 s-triazole Schiff-base carboxylic acid derivatives(7a-7l)were designed and synthesized with both functionalized sulfanylacetic acid and Schiff-base moieties as the modified side-chain for the C-3 bioisosteric s-triazole ring of pefloxacin(1). The structures were characterized by elemental analysis and spectral data, and the in vitro anti-tumor activity of the title compounds against SMMC-7721, L1210 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds possessed more significantly anti-proliferative activity than either the parent 1 or the corresponding amine intermediates(6). In particular, the title compound bearing a fluorine atom(7j)and compound bearing a nitro group attached to benzene ring(7l)were comparable to the control doxorubicin against SMMC-7721 cells with an IC₅₀ value of micro-molar concentration, respectively. It suggests that s-triazole ring modified with functional side-chain moieties instead of the C-3 carboxylic group is favorable to the improvement of antitumor activity.