中文摘要：

目的 寻找氟喹诺酮由抗菌活性转化为抗肿瘤活性的结构修饰策略。方法 用噁二唑杂环作为恩诺沙星（化合物1）C-3羧基的等排体,设计合成了12个新的噁二唑类目标化合物（3a-3l）,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 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）的活性。构效关系表明,苯环带羟基或氟原子或磺酰胺基化合物的活性强于其他取代基化合物的活性,其活性与对照阿霉素的活性相当。结论 氟喹诺酮C-3羧基并非是喹啉酮羧酸类抗肿瘤活性所必需的药效团,用噁二唑杂环替代可显著提高其抗肿瘤活性。

英文摘要：

Objective To explore an efficient strategy for a conversion of antibacterial fluoroquinoles into an- titumor fluoroquinolones. Methods An oxadiazole ring used as the bioisostere of the C-3 carboxylic group of enrofloxacin（1） ,twelve novel oxadiazole derivatives were designed and synthesized as the title compounds 3a-31. The structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activities against SMMC - 7721, L1210 and HL60 cell lines were also evaluated by a MTT assay. Results The preliminary pharmacological results showed that the title compounds exhibited more significantly anti- pro-liferative activity than the parent （1）. The SAR revealed that some title compounds bearing hydroxyl group,fluorine atom or sulfonamide group attached to benzene ring had a potent cytotoxicity compared to doxorubicin. Conclusions The result suggests that it is not necessary for the C-3 carboxylic group of fluoro- quinolones as an antitumor pharmacophore of quinolinone carboxylic acids, but that the replacement of ox- adiazole ring is able to significantly increase the antitumor activity.