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基于抗菌氟喹诺酮作用靶拓扑异构酶设计发展新型抗肿瘤氟喹诺酮药物已成为新的研究方向.为扩展氟喹诺酮C-3稠杂环体系的研究领域,以恩诺沙星1为起始原料经C-3羧基反应到C-31-氨基-5-巯基-均-三唑(5),与氯乙酸缩环合到C-3均三唑[3,4-b][1,3,4]噻二嗪-6-酮(7),接着与取代苯甲醛缩合得C-37-取代苯甲叉基-均三唑[2,1-b][1,3,4]噻二嗪-6-酮(8)目标化合物.新化合物的结构经元素分析和光谱数据表征,用MTT方法评价了它们体外对CHO,HL60和L12103种癌细胞株的体外生长抑制活性.结果表明,所合成的11个新化合物中均具有潜在的体外抑制癌细胞生长活性,其中氨基均三唑硫乙酸中间体6及目标化合物8活性最强,其IC50值已达到或接近微摩尔浓度,预示氟喹诺酮类抗菌剂的C-3位稠杂环抗肿瘤构-效关系值得进一步研究.
The development of new antitumor fluoroquinolone drugs based on the target topoisomerase targeting to fluoroquinolone has become a new research direction.In order to expand the research field of fluoroquinolone C-3 fused heterocyclic system, enrofloxacin 1 is used as a starting material Reaction of C-3 carboxyl with C-31-amino-5-mercapto-homo-triazole (5) followed by condensation with chloroacetic acid to C-3 tritriazolo [3,4- b] 4] thiadiazin-6-one (7), followed by condensation with a substituted benzaldehyde to give C-37-substituted benzylidene-homotriazolo [2,1- b] [1,3,4] thiadiazine (8) The structure of the new compounds The structures of the new compounds were characterized by elemental analysis and spectral data, and MTT assay was used to evaluate their in vitro growth inhibitory activity on CHO, HL60 and L1210 cancer cell lines.The results showed that the synthesized Of the 11 new compounds all have the potential to inhibit the growth activity of cancer cells in vitro. Among them, amino-S-triazinethioacetic acid intermediate 6 and target compound 8 have the strongest activity, and their IC50 values have reached or approached micromolar concentrations, indicating that fluoroquinolones Antibacterial agents C-3 fused heterocyclic ring structure-activity relationship worth further study.