氟喹诺酮-3-N-酰胺类衍生物的合成与抗肿瘤活性  

Syntheses and Antitumor Activities of Fluoroquinolone-3-N-Amide Derivatives

作　　者：沈睿智 曾天映 张海惠 黄文龙[4] 胡国强[5] Shen Ruizhi;Zeng Tianying;Zhang Haihui;Huang Wenlong;Hu Guoqiang(College of pharmacy,Henan University,Kaifeng,475001;College of Chemistry and Molecular Sciences,Wuhan University,Wuhan,430070;Xinke College,Henan Institute of Science and Technology,Xinxiang,453003;Center for Drug Discovery,China Pharmaceutical University,Nanjing,210009;Institute of Drugs,Henan University,Kaifeng,475001)

机构地区：[1]河南大学药学院,开封475001 [2]武汉大学化学与分子科学学院,武汉430070 [3]河南科技学院新科学院,新乡453003 [4]中国药科大学新药研究中心,南京210009 [5]河南大学药物研究所,开封475001

出　　处：《化学通报》2020年第8期730-734,共5页Chemistry

基　　金：国家自然科学基金项目(20872028,21072045);河南省科技发展计划项目(162102310392)资助。

摘　　要：为扩展氟喹诺酮由抗菌活性向抗肿瘤活性转化的结构修饰策略,利用药效团生物电子等排及其拼合和骨架迁越药物化学分子构建方法,以酰胺基作为氟喹诺酮C-3位羧基的生物电子等排体,氟喹诺酮骨架为酰胺基的功能修饰基,设计合成了氟喹诺酮-3-N-酰胺类目标化合物。其结构经元素分析和光谱数据确证。体外抗肿瘤实验结果表明,目标化合物对Hep-3B细胞和Capan-1细胞的抗增殖活性均显著强于母体环丙沙星的活性,尤其对Hep-3B细胞的抑制活性最强。因此,用酰胺基来替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。To expand an efficient strategy for the conversion of antibacterial activity of fluoroquinolones into an antitumor activity,utilizing pharmacophore bioelectronics isosteric and its flattening and skeleton migration medicinal molecule construction method,a series of fluoroquinolone-3-N-amide compounds were synthesized by using amide group as the bioisostere of the fluoroquinolone C-3 carboxyl group and fluoroquinolone skeleton as a functional modification group,and their structures are confirmed by elemental analysis and spectral data.The results of in vitro antitumor activity showed that the anti-proliferative activity of the target compounds against the two experimental tumor cells(Hep-3 B、Capan-1)was significantly stronger than that of the raw material ciprofloxacin,suggesting that replacing the C-3 carboxyl group with an amide group is beneficial to improve the antitumor activity of the quinolones,which provides a new structural modification pathway for transforming antibacterial activity of fluoroquinolone to antitumor activity.

关 键 词：氟喹诺酮 酰胺 生物电子等排 抗肿瘤活性 

分 类 号：TQ460.1[化学工程—制药化工]