<br>新型7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮衍生物的设计、合成及抑菌活性,Heliyon

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新型7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮衍生物的设计、合成及抑菌活性
Heliyon ( IF 3.4 ) Pub Date : 2024-01-20 , DOI: 10.1016/j.heliyon.2024.e24589
Shicheng Hou _{1,

2} , Tai Li ₁ , Jiangqing Yan ₁ , Dong Cai _{1,

3} , Yang Peng ₁ , Haibo Zhang ₁ , Feng Tong ₂ , Haiming Fan ₄ , Xiaoping Liu ₁ , Chun Hu ₁

Affiliation

基于观察到的 1,2,4-三嗪-5-酮衍生物及其环状类似物的生物活性，在噻唑并三嗪酮支架的 3 位含有酯部分化合物 3a-3g、羧酸部分化合物 4a-4g 和哌嗪酰胺部分化合物 5a-5k 的新型 7H-噻唑并三嗪-5-酮衍生物系列。通过 X 射线单晶衍射分析表征了 1,2,4-三嗪环的 N2 位区域选择性地发生分子间环化。针对一些细菌菌株测定目标化合物的体外生物活性。与环丙沙星相比，化合物 3g 和 4g 表现出更优异的抗菌活性，尤其是对金黄色葡萄球菌和大肠杆菌的活性，表明苄基对位的氟将是最佳选择。此外，具有羧酸部分的化合物 4e-4g 可以增强抗菌活性。发现含有大体积 1-（取代苯基）哌嗪部分的化合物 5g-5k 的生物活性略低。与环丙沙星类似，目标化合物与 DNA 拓扑异构酶 II 的对接结果表明，目标化合物与羧酸部分的羧基与蛋白质中的 Mg2+ 具有关键的盐桥相互作用。

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Design, synthesis and antibacterial activity of novel 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives

Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds 3a-3g, carboxylic acid moiety compounds 4a-4g and piperazine amide moiety compounds 5a-5k at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The in vitro biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds 3g and 4g exhibited more excellent antibacterial activity, especially the activity against Staphylococcus aureus and Escherichia coli, showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds 4e-4g with carboxylic acid moiety can enhance the antibacterial activity. Compounds 5g-5k containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg2+ in the protein.

更新日期：2024-01-20

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