氟喹诺酮C-3稠杂环噻唑并均三唑衍生物的合成及抗肿瘤活性(Ⅵ)  

Synthesis and Antitumor Activity of Fluoroquinolone C-3 Fused Heterocyclic Thiazolo[3,2-b][1,2,4]triazole Derivatives(Ⅵ)

作　　者：吴书敏[1] 闫强[1] 倪礼礼 谢玉锁 高留州[1] 刘英杰[2] 黄文龙[3] 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]河南大学医学院微生物学教研室,河南开封475001 [3]中国药科大学新药研究中心,南京210009

出　　处：《中国药学杂志》2016年第5期353-357,共5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资助项目(15A350004)

摘　　要：目的为发现抗菌氟喹诺酮向抗肿瘤活性转化的有效修饰策略。方法以均三唑为氧氟沙星C-3羧基的等排体、通过缩环合反应设计了C-3噻二唑并均三唑稠杂环目标化合物(5a^5l,6a^6l)。用元素分析和光谱数据确证化合物的结构,用MTT方法评价了目标化合物对体外培养的SMMC-7721、Capan-1和HL60 3种癌细胞株的抗增值活性。结果合成了12个新型结构的C-3稠杂环目标化合物,体外抗肿瘤活性强于母体1和相应中间体硫醚酮5的活性,但弱于硫醚酮缩氨基硫脲化合物6的活性。结论 C-3稠杂环等排体的结构修饰值得进一步研究。OBJECTIVE To discover an efficient strategy for conversion of the antibacterial activity of fluoroquinolone drugs to antitumor activity. METHODS Novel title fused heterocyclic C-3 thiazolo[3,2-b] [1,2,41triazole derivatives（5,6） were designed by using a s-triazolc ring as the bioisostere and modifying it by a fused condensation-cyclization reaction. The structures were validated by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against three tested tumor cell lines was evaluated by MTT assay. RESULTS Twelve title compounds were synthesized from ofloxacin and exhibited more significant antiproliferative activity than both of parent ofloxaein 1 and the corresponding intermediate sulfide ketones 5, but displayed a slightly weaker activity than the corresponding sulfide ketone thiosemi-carbazones 6. CONCLUSION An efficient structure modification strategy for the fused heterocyclic core of thiazolotriazole used as the C-3 bioisostere warrants further development.

关 键 词：氟喹诺酮 氧氟沙星 稠杂环 噻唑并均三唑 等排体 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]