氟喹诺酮C-3杂环化合物的设计、合成与抗肿瘤活性研究：环丙沙星双-噁二唑甲硫醚衍生物(英文)  

Part Ⅳ:design,synthesis and antitumor activity of fluoroquinolone C-3 heterocycles:bis-oxadiazole methylsulfide derivatives derived from ciprofloxacin

作　　者：胡国强[1] 侯莉莉[1] 王国强[1] 段楠楠[1] 温晓漪[1] 曹铁耀[1] 银俊[1] 王伟[1] 谢松强[1] 黄文龙[2] 

机构地区：[1]河南大学化学生物学研究所,河南开封475001 [2]中国药科大学新药研究中心,江苏南京210009

出　　处：《药学学报》2012年第8期1017-1022,共6页Acta Pharmaceutica Sinica

基　　金：Project supported by the National Natural Science Foundation of China(20872028,21072045)

摘　　要：为进一步探究发现抗肿瘤氟喹诺酮候选化合物的有效策略,用噁二唑杂环作为环丙沙星的羧基电子等排体得中间体C-3噁二唑硫醇(5),与噁二唑氯甲烷(6a–6h)缩合形成双-噁二唑甲硫醚(7a–7h),再与碘甲烷成哌嗪季铵盐(8a–8h),其结构经元素分析和光谱数据确证,评价了体外对CHO、HL60和L1210 3种肿瘤细胞的生长抑制活性。初步的药理结果表明,哌嗪季铵盐(8)的活性高于相应游离碱(7)的活性。To explore an efficient strategy for further development of anticancer fluoroquinolone candidates derived from ciprofloxacin,a heterocyclic ring as the bioisosteric replacement of C3 carboxyl group led to a key intermediate,oxadiazole thiol（5）,which was further modified to the bis-oxadiazole methylsulfides（7a–7h） and the corresponding dimethylpiperazinium iodides（8a-8h）,respectively.Structures were characterized by elemental analysis and spectra data,and their anticancer activities in vitro against CHO,HL60 and L1210 cancer cells were also evaluated by MTT assay.The preliminary results show that piperazinium compounds（8） possess more potent activity than that of corresponding free bases（7）.

关 键 词：氟喹诺酮 等排体 双-噁二唑 硫醚 哌嗪季铵盐 抗癌活性 

分 类 号：R916[医药卫生—药学]