氟喹诺酮C-3羧基等排体的合成及抗肿瘤活性Ⅲ.均三唑噁二唑甲硫醚衍生物  

Synthesis and antitumor activity of fluoroquinolone C-3 isostere Ⅲ: s-triazole oxadiazole methylsulfide derivatives from pefloxacin

作　　者：许秋菊[1] 侯莉莉[1] 仵钊锋 岳喜波[1] 胡国强[1] 黄文龙[2] 

机构地区：[1]河南大学化学生物研究所,开封475001 [2]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》2013年第6期511-514,共4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：为寻找由氟喹诺酮抗菌活性到抗肿瘤活性转化的有效途径,用均三唑和噁二唑分别作为培氟沙星C-3羧基的等排体和修饰基,设计合成了10个未见文献报道的双杂环硫醚1-乙基-6-氟-7-(4-甲基哌嗪-1-基)-3-[5-(5-芳基-[1,3,4]噁二唑-2-甲硫基)-4H-[1,2,4]-三唑-3-基]-喹啉(1H)-4-酮新化合物(7a^7j)。结果显示:对L1210、HL60和CHO 3种肿瘤细胞的体外抑制活性显著高于母体培氟沙星,表明C-3羧基不是抗肿瘤活性所必需的药效团,可被杂环等排体替换,进一步扩展了结构修饰的途径。To discover an efficient route for the conversion of antibacterial fluoroquinolone to antitumor activity, s-triazole ring as an isostere modified by an oxadiazole ring corresponding to the C-3 carboxylic acid group for pefloxacin resulted in ten new title compounds, 1 -ethyl- 6-fluoro-（4-methylypiperazin-l-yl） -3-[ 5-（ 5-aryl-[ 1,3, 4] oxadiazol-2-methylsulfanyl） -4H-[ 1,2, 4] -triazol-3-yl] -quinolin （ 1 H） -4-ones （ 7 a-7j）. Their structures were char- acterized by corresponding spectral data. The in vitro antitumor activity of the title compounds against L1210, HL60 and CHO cell lines exhibited significantly higher potency than parent pefloxacin. Thus, it suggests that it is necessary to retain a heterocycle instead of a C-3 carboxyl for antitumor fluoroquinolone compounds.

关 键 词：氟喹诺酮 均三唑 噁二唑 硫醚 生物电子等排体 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]