培氟沙星C-3(绕丹宁不饱和酮)酰胺的合成及抗肿瘤活性  

Synthesis and antitumor activity of pefloxacin C-3(rhodanine unsaturated ketone)amide derivatives

作　　者：杨彤[1] 汪学猛 王蕊 黄文龙[3] 胡国强[1] 

机构地区：[1]河南大学化学生物学研究所,开封475001 [2]河南大学护理与健康学院,开封475001 [3]中国药科大学新药研究中心,南京210009

出　　处：《中国药科大学学报》2017年第5期543-547,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)~~

摘　　要：为发现将抗菌药氟喹诺酮转化为抗肿瘤药的结构修饰新策略,用酰氨基和绕丹宁不饱和酮分别作为培氟沙星(1)C-3羧基的等排体和修饰基,设计合成了12个新的培氟沙星C-3(绕丹宁不饱和酮)酰胺类目标化合物(6a^6l),其结构经元素分析和光谱数据确证。体外抗增殖活性结果显示,目标化合物对Hep-3B、Capan-1和L1210 3种肿瘤细胞株的活性显著高于母体培氟沙星,含芳杂环或氟苯基化合物的活性与对照抗肿瘤药阿霉素相当。由此推测酰氨基绕丹宁不饱和酮杂合骨架替代C-3羧基有利于提高氟喹诺酮的抗肿瘤活性。To explore a new strategy for the transformation of antibacterial activity of fluoroquinolone into antitumor activity,twelve new title compounds,1-ethyl-6-fluoro-7-（4-methyl-pipreazin-1-yl）-quinolin-4-one-3-carboxylicacid（5-arylidene-2-thioxo-1,3-thiozolidin-2,4-dione-3-yl）amides（6a-6l）,were designed and synthesized with an amide group and a rhodanine unsaturated ketone moiety as an isostere and modified group,respectively,from pefloxacin（1）.Their structures were characterized by elemental analysis and spectral data.The in vitro antitumor activity of the title compounds against Hep-3B,Capan-1 and L1210 cell lines exhibited more significant potency than pefloxacin.The compounds with aromatic heterocyclic or flurophenyl displayed comparable activity to the comparasion doxorubicin.Thus,rhodanine unsaturated ketone hybrided amide group as an isostere of the C-3 carboxylic acid group appears to be an alternative route for further design of antitumor fluoroquinolone.

关 键 词：氟喹诺酮 酰胺 绕丹宁 不饱和酮 抗肿瘤活性 合成 

分 类 号：R914[医药卫生—药物化学]