氟喹诺酮C-3均三唑硫乙酸席夫碱的合成及抗菌抗肿瘤活性检测  

Synthesis of fluoroquinolone C-3 s-triazole derivatives modified with sulfanylacetic acid and Schiff-base and their antibacterial and antitumor activities

作　　者：张会丽 李珂 胡国强[2] 黄文龙[3] 

机构地区：[1]郑州工业应用技术学院药学院,郑州451150 [2]河南大学药学院,河南开封475001 [3]中国药科大学新药研究中心,南京210009

出　　处：《郑州大学学报（医学版）》2017年第2期154-159,共6页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金面上资助项目20872028;21072045

摘　　要：目的:探讨由抗菌氟喹诺酮到抗肿瘤氟喹诺酮的构建新策略。方法:用均三唑杂环作为环丙沙星C-3羧基的生物电子等排体,硫乙酸和亚胺席夫碱为其功能修饰侧链,合成了10个新氟喹诺酮C-3均三唑硫乙酸席夫碱目标化合物(7a^7j),其结构经元素分析和光谱数据确证,评价其体外对标准金黄色葡萄球菌和大肠埃希菌及SMMC-7721、L1210和HL60 3种癌细胞的生长抑制作用。结果:目标化合物的抑菌活性明显低于母体环丙沙星,但抗肿瘤活性显著高于母体化合物,尤其是苯环含有羟基或氟原子的化合物,其IC50已达到微摩尔级,与对照阿霉素相当。结论:均三唑杂环作为氟喹诺酮C-3羧基的等排体,且被功能基侧链修饰是构建抗肿瘤氟喹诺酮分子的有效策略。Aim： To discover an efficient strategy for a conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones. Methods： Ten novel fluoroquinolone C-3 s-triazole derivatives were designed and synthesized with an s-triazole ring as the C-3 bioisostere modified by both functionalized sulfanylacetic acid and imine Schiff-base side chains from ciprofloxacin,respectively. The structures of the title compounds were characterized by elemental analysis and spectral data,and the in vitro antibacterial activities against S. aureus and E. coli and antitumor activities against SMMC-7721,L1210,and HL60 cells were evaluated. Results： The title compounds demonstrated poorer antibacterial activity but more significant antitumor activity than the parent,respectively. In particular,compounds bearing a fluorine atom or nitro group attached to benzene ring were comparable to the control doxorubicin with an IC50 values of micro-molar concentration,respectively.Conclusion：It suggests that an azole modified with functionalized side-chain as the bioisosteric replacement of the C-3 carboxylic group is favorable to improvement of antitumor activity.

关 键 词：氟喹诺酮 均三唑 生物电子等排体 席夫碱 硫乙羧酸 抗菌抗肿瘤活性 

分 类 号：R979.1[医药卫生—药品]