中文摘要：

目的寻找氟喹诺酮C-3羧基等排体噁二唑的修饰方法,提高其衍生物的抗肿瘤活性。方法基于药效团与骨架跃迁原理,用功能基侧链硫乙酰腙类作为C-3等排体的修饰基团,设计合成了氟喹诺酮C-3噁二唑硫乙酰腙目标化合物。用MTT方法评价了目标化合物对体外培养肿瘤细胞的生长抑制活性。结果合成14个目标化合物,体外均显示潜在的抗肿瘤活性,尤其是修饰基含有羧基取代苯环的化合物其抗肿瘤活性与多柔比星的活性相当。结论吸电子基酰腙作为C-3等排体的修饰基团值得关注。

英文摘要：

OBJECTIVE To explore an efficient modification strategy for a bioisotere antibacterial fluoroquinolon-3-yl carboxylic acid group for developing compounds with improved antitumor activity. METHODS Novel title 2-（ fluoroquinolon-3-yl）-oxadiazole-5-sulfanylacetylhydrazone derivatives were designed on the basis the pharmacophore skeleton transition principle,and the in vitro activity the title compounds was evaluated by MTT assay. RESULTS Fourteen target compounds were synthesized from ofloxacin and exhibited more potent antitumor activity than the parent compound,especially the compounds with a carboxylic group-substitued phenyl ring as a modified group around the bioisostere,which had comparable activity to doxorubicin. CONCLUSION A hydrazone with electron-withdrawing substituents warrants further development as the modified side-chain for the C-3 bioisostere.