中文摘要：

目的寻找转化抗菌氟喹诺酮到抗肿瘤氟喹诺酮的有效策略。方法用酰腙作为恩诺沙星1C3羧基的生物电子等排体,合成了12个新的恩诺沙星酰腙（3a-31）目标化合物,其结构经元素分析和光谱数据确证。用MTT方法评价了目标化合物体外对SMMC-7721、L1210和HL60 3种癌细胞的生长抑制活性。结果酰腙目标物对3种实验癌细胞的生长抑制活性显著强于母体化合物1,苯环带吸电子化合物的活性强于供电子化合物的活性,尤其对肝癌SMMC-7721细胞的活性明显高于对白血病细胞L1210和HL60的活性。结论氟喹诺酮羧基并非是抗肿瘤活性所必需的药效团,其被酰腙取代可显著提高其抗肿瘤活性。

英文摘要：

Objective To explore an efficient strategy for a transformation of antibacterial fluoroquinoles into antitumor fluoroquinolones. Methods Using acylhydrazone as bioisostere of the C3 carboxylic group,twelve novel fluoroquinolone C-3 acylhydrazones 3a-3l were synthesized from enrofloxacin 1,respectively. The structures of the title compounds were characterized by elemental analysis and spectral data,and their in vitro antitumor activities against SM M C-7721,L1210 and HL60 cell lines were evaluated by a M TT assay. Results Interestingly,the compounds 3a-3l exhibited more significantly inhibitory activity than the parent compound 1,in which compounds with electron-withdrawing group showed more potent cytotoxicity than that of compounds with electron donating group. M eanwhile,the title compounds had a better activity against SM M C-7721 cell line than the other tested cancer cell lines. Conclusions The C-3 carboxylic group is not necessary for the antitumor activity of fluoroquinolones,an acylhydrazone as bioisosteric replacement of the C-3 carboxylic group is favorable for the improvement of the antitumor activity.