3-(5-苄叉基噻唑并均三唑酮)氟喹诺酮类化合物的合成及其抗肿瘤活性  

Synthesis and antitumor activity of 3-( 5-benzylidenethuzolo-triazlone) fluoroquinolones

作　　者：姜亚玲 李珂 黄文龙[2] 胡国强[3] JIANG Yaling;LI Ke;HUANG Wenlong;HU Guoqiang(Department of Medicial Chemistry,Zhengzhou University of Industrial Technology Zhengzhou 451150;Centre of Drug Discovery,China Pharmaceutical University,Nanjing 210009;School of Pharmacy,Henan University,Kaifeng 475001,China)

机构地区：[1]郑州工业应用技术学院药物化学教研室,郑州451150 [2]中国药科大学新药研究中心,南京2100091 [3]河南大学药学院,开封475001

出　　处：《中国药科大学学报》2018年第6期671-675,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.20872028;No.21072045);河南省科技发展计划资助项目(No.16210231039)~~

摘　　要：为发现氟喹诺酮抗菌活性向抗肿瘤活性转化的有效方法,用稠杂环噻唑并均三唑酮作为培氟沙星(1) C-3羧基的生物等排体,芳甲叉基为其修饰基团,设计合成了12个新的C-3噻唑并均三唑不饱和酮目标化合物(6a～6l),其结构经元素分析和光谱数据确证,评价了它们体外对SMMC-7721、Capan-1和HL60 3种肿瘤细胞株的抗增殖活性。初步药理筛选结果表明,目标化合物的活性显著高于母体化合物1的抗肿瘤活性,含氟苯基和邻甲氧苯基化合物的活性与对照抗肿瘤药阿霉素相当。因此,噻唑并均三唑不饱和酮骨架替代氟喹诺酮C-3羧基有利于提高其抗肿瘤活性。To discover an efficient approach for the conversion of antibacterial fluoroquinolones into an antitumor activity,a fused heterocycle ring core,thiazolo[3,2-b][1,2,4]triazol-5-one was used as an isostere and further modified with an arylidene group.Then,12novel C-3fused heterocyclic unsaturated ketones,1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-[6-arylidene-thiazolo[3,2-b][1,2,4]triazol-5(6H)-one-3-yl]-quinolon-4(1H)-ones(6a-6l),were designed and synthesized from pefloxacin(1).The structures were characterized by elemental analysis and spectral data,and the in vitro antitumor activity of the title compounds against SMMC-7721,Capan-1and HL60cell lines was evaluated.The preliminary pharmacological results demonstrated that the title compounds exhibited more significantly antiproliferative activity than the parent1.The compounds with fluorophenyl or o-methoxyphenyl showed comparable activity to the comparasion doxorubicin.Thus,it appears to be an alternative route for a fused heterocyclic unsaturated ketone as an isostere of the C-3carboxylic group to improve the antitumor activity.

关 键 词：氟喹诺酮 均三唑 噻唑 噻唑并均三唑 不饱和酮 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]