喹诺酮类化合物的设计、合成与抗肿瘤活性研究  

Design,Synthesis and Antitumor Activity of Quinolone Derivatives

作　　者：李杰[1] 金懿[1] 寿凯军 吕延文[1,3] 

机构地区：[1]衢州学院化学与材料工程学院,浙江衢州324000 [2]诸暨市人民医院,浙江绍兴312000 [3]浙江工业大学药学院制药工程教育部重点实验室,杭州310014

出　　处：《中国药学杂志》2013年第23期2055-2060,共6页Chinese Pharmaceutical Journal

基　　金：浙江省自然科学基金项目资助项目(Y2100908)

摘　　要：目的设计合成喹诺酮类化合物并研究其体外抗肿瘤活性。方法以现有的喹诺酮类药物（诺氟沙星和环丙沙星）为原料，对其进行结构改造，在哌嗪环的N上引入由芳基磺酰氯和单氰胺反应形成的甲脒基芳磺酰胺侧链。采用噻唑蓝（MTT）法考察所合成的目标化合物对A549、HL450、Hela等肿瘤细胞的抑制活性。并运用DiscoveryStudio软件的CDOCKER模块对所设计的化合物进行分子对接研究。结果合成14个新化合物，其结构经’H．NMR、ESI和HRMS确定，活性测试结果表明，大部分化合物有一定的抗肿瘤活性。结论该类喹诺酮类衍生物的抗肿瘤活性值得进一步研究。OBJECTIVE To synthesize quinolone derivatives and investigate their anti-tumor activities in vitro. METHODS A series of quinolone derivatives were designed and synthesized from Norfloxacin or Ciprofloxacin with N-（phenylsulfonyl） formimidamide. Their anti-tumor activities in vitro were evaluated for A549 ,HL-60, Hela cells by MTY assay. Molecular docking studies were performed with the Discovery Studio to afford the ideal interaction mode of the compound into the binding site of the Topo I. RESULTS Four- teen novel compounds were synthesized and the structures were characterized by I H-NMR, ESI and HRMS. M3T assay showed that most quinolone derivatives exhibited some anti-tumor activities. CONCLUSION These quinolone derivatives are worth further being developed.

关 键 词：喹诺酮类化合物 抗肿瘤活性 化学合成 TOPO I抑制剂 

分 类 号：R284[医药卫生—中药学]