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目的:寻找转化抗菌氟喹诺酮到抗肿瘤氟喹诺酮的有效策略。方法:用酰腙作为N-甲基环丙沙星C-3羧基的生物电子等排体,合成了12个环丙沙星酰腙目标化合物,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:酰腙目标物对3种实验癌细胞的生长抑制活性显著强于母体环丙沙星。构-效关系表明,苯环带吸电子化合物的活性强于供电子化合物的活性,尤其带羧基和磺酰胺基化合物的活性强于其他取代基化合物的活性。结论:氟喹诺酮C-3羧基并非是抗肿瘤活性所必需的药效团,被酰腙取代可提高其抗肿瘤活性。
Objective: To find an effective strategy to transform fluoroquinolone into anti-tumor fluoroquinolone. METHODS: Twelve ciprofloxacin hydrazone compounds were synthesized using acylhydrazone as the bioisostere of C-3 carboxyl group of N-methyl ciprofloxacin. Its structure was confirmed by elemental analysis and spectral data. The inhibitory activity of the target compounds on the growth of SMMC-7721, L1210 and HL60 cancer cells in vitro was evaluated by MTT method. Results: The inhibitory activity of acylhydrazone on the three experimental cancer cells was significantly stronger than that of ciprofloxacin. The structure-activity relationship shows that the benzene ring electron-withdrawing compounds are more active than the electron-donating compounds. In particular, the carboxyl- and sulfonamide-based compounds are more active than the other substituent compounds. CONCLUSION: Fluoroquinolone C-3 carboxyl group is not a necessary pharmacophore for antitumor activity. Substitution of acylhydrazone can increase its antitumor activity.