C-3噻唑并均三唑取代的培氟沙星衍生物的合成及抗肿瘤活性(Ⅸ)

Synthesis and antitumor activity of C-3 thiazolo [3, 2-b ] [1, 2, 4 ] triazolesubstituted pefloxacin derivatives

为寻找抗肿瘤氟喹诺酮类化合物的新方法,用稠杂环核作为培氟沙星(1)C-3羧基的生物电子等排体,设计合成了12个新的噻唑并[3,2-b][1,2,4]三唑类目标化合物(6a^6l),其结构经元素分析和光谱数据确证。选择SMMC-7721、L1210和HL60 3种肿瘤细胞株进行体外抗增殖活性实验,结果表明目标化合物的抗肿瘤活性高于先导化合物1和相应的开环中间体硫醚酮(5a^5l),其中苯环上有羟基或氟原子取代的目标化合物对SMMC-7721肿瘤细胞显示出较强的活性。基于此,噻唑并均三唑稠杂环可作为氟喹诺酮C-3羧基的等排体用于抗肿瘤氟喹诺酮类化合物的设计。

To search for fluoroquinolones（FQs）with antitumor activity;the C-3 carboxylic acid group of peflox-acin （1）was replaced by fused heterocyclic core;and twelve novel thiazolo[3;2-b][1;2;4]triazole heterocycles（6a-6l）were designed and synthesized.The structures of target compounds were characterized by elemental anal-ysis and spectral data.The results of the in vitro antiproliferative effect on SMMC-7721;L1210 and HL60 cell lines showed that the title compounds exhibited more significant antitumor activity than both of the pefloxacin and the corresponding opening-ring intermediates（5 a-5 l）.Among them;the target compounds which possess a ben-zene ring bearing a hydroxyl group （6e）or a fluorine atom （6j）exhibited more potent antiproliferative effect on SMMC-7721 cells than other compounds.Therefore;the antitumor fluoroquinolones can be designed by replacing the C-3 carboxylic acid group of fluoroquinolones with the thiazolo[3;2-b][1;2;4]triazole moiety.