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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,用噁二唑作为修饰杂环,设计合成了C3双异杂环均三唑噁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-[1,3,4]-噁二唑-2-甲硫基)-4H-[1,2,4]-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 find out the effective C3 bioactive bioisostere of antifungal fluoroquinolone converted into anti-tumor activity. Methods The triazole heterocycle was used as an isostere of C3 carboxyl group of the antibacterial fluoroquinolone ofloxacin (1). The oxadiazole was used as the modified heterocycle. The title compound, 6-fluoro-7- (4-methylpiperazin- 1 -yl) 1,8- (2,1- oxopropyl) -3- [5- 4-oxadiazole-2-methylthio) -4H- [1,2,4] -triazol-3-yl] -quinolin- 4 (1H) -one (6a ~ 6j) Blue (MTT) method to evaluate its anti-tumor activity in vitro. Results Ten neo-bis-heterocyclic thioether target compounds were synthesized and the anti-tumor activity in vitro was significantly higher than that of the parent compound of ofloxacin. Conclusion Hetero-triazole heterocycles can be used as effective isomers of C-3 carboxyl.