氟喹诺酮C3杂环取代衍生物的合成及抗肿瘤活性研究(I)：环丙沙星噻二唑希夫碱  

Synthesis and antitumor activity of C3 heterocyclic-substituted fluoroquinolone derivatives (I): ciprofloxacin aminothiodiazole Schiff-bases

作　　者：胡国强[1] 毋晓魁[1] 王新[1] 张智强[1] 谢松强[1] 黄文龙[2] 张惠斌[2] 

机构地区：[1]河南大学药物研究所,河南开封475001 [2]中国药科大学新药中心,江苏南京210009

出　　处：《药学学报》2008年第11期1112-1115,共4页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(20872028);河南省教育厅资助项目(2008A3500013)

摘　　要：为发现氟喹诺酮类抗肿瘤先导化合物,用氨基噻二唑杂环替代环丙沙星(1)C3羧基形成环丙氟喹诺酮氨基噻二唑(2)骨架,然后与芳香醛缩合得到相应的希夫碱目标化合物(3a^3j)。新化合物的结构经元素分析和光谱数据表征,并用MTT法评价了它们体外对SMMC-7721、HL60和L1210 3种癌细胞株的生长抑制活性。结果表明,所合成的11个新化合物均具有潜在的体外细胞毒活性,其中目标化合物3d和3f的IC50值达到微摩尔浓度数量级。这表明,氟喹诺酮类抗菌剂的3位羧基不是抗肿瘤活性所必需的,而被功能化修饰的杂环取代衍生物作为新结构抗肿瘤先导物具有进一步研究和开发的价值。To discover a novel antitumor lead compound derived from fluoroquinolone, C3 carboxyl group of ciprofloxacin （1） was replaced with heterocyclic ring to form cyclopropyl fluoroquinolone aminothiadiazole scaffold （2）, then reacted with aromatic aldehydes to give the Schiff bases compounds （3a-3j）. The structures of new compounds were characterized by element analysis and spectral data, and their in vitro antitumor activity against SMMC-7721, HL60 and L1210 cell lines was evaluated by MTI＂ assay via the respective IC50 values. The bioactive assay showed that eleven thiadiazole-substituted ciprofloxacin derivatives displayed potential cytotoxicity against the tested cancer cell lines, where the IC50 values of compounds 3d and 3f reached micromolar concentration. Therefore, the C3 carboxyl group of fluoroquinolone is not necessary to antitumor activity. Functionally modified heterocycle-substituted fluoroquinolone as potent antitumor lead compound is valuable for further study.

关 键 词：氟喹诺酮 噻二唑 希夫碱 抗肿瘤活性 

分 类 号：R916.696[医药卫生—药学]