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基于抗菌氟喹诺酮的作用机制,一个有效的转化其抗菌活性到抗肿瘤活性的修饰途径被进一步发展。用稠杂环均三唑并噻二嗪作为环丙沙星(CFX)羧基的生物电子等排体,设计合成了1-环丙基-6-氟-7-哌嗪-1-基-3-(6-取代苯基-7H-[1,2,4]三唑并[3,4-b][1,3,4]噻二嗪-3-基)-喹啉-4(1H)-酮(5a～5e)及相应的N-乙酰稠杂环化合物(6a～6e)。同时发现,均三唑并噻二嗪在热醋酐中可发生噻二嗪环的缩环挤出硫反应到相应的三乙酰化吡唑并均三唑新稠环体系(7a～7e)。用MTT法评价了新稠杂环化合物对L1210、CHO和HL60 3种癌细胞株的体外生长抑制活性。结果表明,15个供试化合物的活性(IC50<25μmol.L-1)均显著高于母体化合物CFX的活性(IC50>150μmol.L-1),而且活性按7a～7e>5a～5e>6a～6e顺序递减。
Based on the mechanism of action of the antibacterial fluoroquinolone, an effective modification of its antimicrobial activity to antitumor activity is further developed. In this paper, we designed and synthesized 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3 - (6-substituted phenyl-7H- [1,2,4] triazolo [3,4- b] [1,3,4] thiadiazin-3- (5a ~ 5e) and the corresponding N-acetyl fused heterocyclic compounds (6a ~ 6e). It was also found that all of the triazolylthiadiazoles could occur in thermal acetic anhydride by the ring-extrusion of the thiadiazole ring to the corresponding triazole-acenaphthotriazole new fused ring system (7a ~ 7e). The in vitro growth inhibitory activity of the new fused heterocyclic compounds on three cancer cell lines L1210, CHO and HL60 was evaluated by MTT assay. The results showed that the activities of all the 15 tested compounds (IC50 <25μmol.L-1) were significantly higher than that of the parent compound CFX (IC50> 150μmol.L-1) ~ 6e decreasing order.