CAJ | 학술논문

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HL603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。
위심조항종류불규낙동류화합물적신방법，용주잡배핵작위배불사성（1） C-3최기적생물전자등배체，설계합성료12개신적새서병[3，2-b][1，2，4]삼서류목표화합물（6a～6l），기결구경원소분석화광보수거학증。선택SMMC-7721、L1210화HL603충종류세포주진행체외항증식활성실험，결과표명목표화합물적항종류활성고우선도화합물1화상응적개배중간체류미동（5a～5l），기중분배상유간기혹불원자취대적목표화합물대SMMC-7721종류세포현시출교강적활성。기우차，새서병균삼서주잡배가작위불규낙동C-3최기적등배체용우항종류불규낙동류화합물적설계。
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.