氧氟沙星C-3(绕丹宁不饱和酮)酰胺的合成及抗肿瘤活性  

Synthesis and Antitumor Activity Evaluation of C-3( Rhodanine Unsaturated Ketone) Amides as Ofloxacin Derivatives

作　　者：汪学猛 李书平 杨彤 黄文龙[3] 王蕊 胡国强[1] 

机构地区：[1]河南大学化学生物学研究所,河南开封475001 [2]郑州工业应用技术学院药学应用技术研究所,郑州451150 [3]中国药科大学新药研究中心,南京21009 [4]河南大学护理与健康学院,河南开封475001

出　　处：《中国药学杂志》2018年第3期174-177,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(20872028;21072045);河南省高等学校重点科研项目(15A350004)

摘　　要：目的发现氟喹诺酮由抗菌活性转化为抗肿瘤活性的结构修饰策略。方法以酰胺作为氧氟沙星C-3羧基的等排体、饶丹宁不饱和酮其功能侧链修饰基,设计合成了C-3(饶丹宁α,β-不饱和酮)酰胺类目标化合物(6a^6l),并用元素分析和光谱数据确证化合物的结构、四甲基偶氮唑蓝(MTT)方法评价对体外培养的SMMC-7721、Capan-1和HL603种试验癌细胞株的抗增值活性。结果合成的12个新结构目标化合物的活性显著强于母体氧氟沙星,其中芳杂环取代的化合物对其Capan-1细胞的活性与对照阿霉素相当。结论饶丹宁不饱和酮杂合酰胺骨架作为C-3羧基的等排体有利于提高抗肿瘤活性。OBJECTIVE To explore an efficient strategy for converting the antibacterial activity of fluoroquinolones to antitumor activity. METHODS An amide group as an isostere modified by rhodanine unsaturated ketone moiety corresponding to the C-3 carboxylic acid group resulted in 12 new title C-3 （5-arylidene-2-thioxo-1,3-thiozolidin-2,4-dione-3-yl） amides （6a- 61） from ofloxacin 1. Their structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against three tested cell lines was evaluated by MTT assay. RESULTS Twelve new title compounds were synthesized from ofloxacin and exhibited significantly higher potency than the parent compound ofloxacin. CONCLUSION Using a rhodanine unsaturated ketone hybrided amide group as the C-3 bioisostere is favorable to improve antitumor activity.

关 键 词：氟喹诺酮 氧氟沙星 酰胺 饶丹宁 不饱和酮 抗肿瘤活性 

分 类 号：I197[文学—世界文学]