目的 寻找抗菌氟喹诺酮转化为抗肿瘤活性的C3羧基有效生物电子等排体。方法 均三唑杂环作为抗菌氟喹诺酮氧氟沙星(1)C3羧基的等排体,用NFDE6二唑作为修饰杂环,设计合成了C3双异杂环均三唑NFDE6二唑甲硫醚目标化合物,6-氟-7-(4-甲基哌嗪-1-基)1,8-(2,1-氧丙基)-3-[5-(5-芳基--NFDE6二唑-2-甲硫基)-4H--三唑-3-基]-喹啉-4(1H)-酮(6a~6j),用噻唑蓝(MTT)方法评价其体外抗肿瘤活性。结果 合成了10个新双异杂环硫醚目标化合物,体外抗肿瘤活性显著高于母体化合物氧氟沙星的活性。结论 均三唑杂环可作为C-3羧基的有效等排体。

OBJECTIVE To explore an efficient heterocyclic bioisostere as the C3 carboxylic group of antibacterial fluoroquinolones for further development of antitumor fluoroquinolones. METHODS Using the s-triazole ring as an isosteric replacement of the C3 carboxylic group with another different heterocyclic ring,oxadiazole,as a modified group,new bis-(different azole)methylsulfide derivatives,6-fluoro-7-(4-methyl-piperazin-1-yl)-1,8-(2,1-oxpropyl)-5-[5-(aryl--oxadiazol- 2-methylsulfanyl)-4H--triazol-3yl]-quinolin-4(1H)-ones(6a-6j),were designed from ofloxacin(1). The in vitro antitumor activity of 6a-6j against three cancer cell lines was evaluated by MTT assay. RESULTS Ten title compounds(6a-6j)were synthesized and their structures were characterized by spectral data. They exhibited significantly higher in vitro antitumor potency than the parent compound ofloxacin. CONCLUSION The heterocyclic ring,s-triazole,could be used as an efficient isostere of the C-3 carboxylic group for further development of antitumor fluoroquinolone candidates.