中文摘要：

目的为发现氟喹诺酮C-3羧基等排体的优化方法。方法用噁二唑硫酮杂环替代恩诺沙星（1）C-3羧基,以曼尼希碱作为修饰侧链,设计合成了10个新的恩诺沙星C-3羧基等排体——噁二唑硫酮曼尼希碱目标化合物（4a-4j）,其结构经元素分析和光谱数据确证。用MTT（3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐）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强于母体化合物1和中间体噁二唑酮3的活性,其中以哌嗪和对氟苯胺为胺供体目标化合物对SMMC-7721细胞的活性高于其他胺供体化合物的活性,其活性与对照阿霉素的活性相当。结论噁二唑硫酮杂环可作为氟喹诺酮C-3羧基的等排体,用曼尼希碱侧链修饰可显著提高其抗肿瘤活性。

英文摘要：

Objective To discovery an optimization method for the bioisostere of the C-3 carboxylic acid group of fluoroquinolones. Methods An oxadiazolone thione heterocycle modified by a M annich-base side chain replace the C-3 carboxylic group of enrofloxacin,ten novel title oxadiazolone thione M annich-base derivatives 4a-4j were designed and synthesized. The structures of the title compounds were characterized by elemental analysis and spectral data,and the anti-proliferative activity against SM M C-7721,L1210 and HL60 cell lines was also evaluated by a M TT method. Results The results revealed that the title compounds 4a-4j showed an more improved anti-proliferative activity against the three tested tumor cells than both enrofloxacin and the synthesized intermediate 3. Among them,two title compounds（ 4e and 4j） derived from the corresponding amino donors of methylpiperazine and para-fluoroaniline exhibited a better activity against SM M C-7721 cells than the other compounds with a lowIC50 value compared to control doxorubicin. Conclusions It is suitable for an oxadiazolone thione ring modified by M annich-base moiety as the bioisosteric replacement of the C-3 carboxylic group to improve the antitumor activity of fluoroquinolones.