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］triazole-substituted pefloxacin derivatives
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摘要: 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。Abstract: To search for fluoroquinolones(FQs)with antitumor activity, the C-3 carboxylic acid group of pefloxacin( 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 analysis 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( 5a - 5l ). Among them, the target compounds which possess a benzene 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.
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Keywords:
- fluoroquinolone /
- s-triazole /
- thiazole /
- thiazolotriazole /
- antitumor activity
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