【作者】 卢伟； 王迪； 崔长军； 董梅； Moon-Young Yoon； 王建国；

【Author】 Wei Lu;Di Wang;Chang-Jun Cui;Mei Dong;Moon-Young Yoon;Jian-Guo Wang;State-Key Laboratory and Institute of Elemento-Organic Chemistry,Nankai University;Department of Clinical Laboratory,309 Hospital of Chinese People’s Liberation Army;Department of Chemistry,Institute of Natural Sciences,Hanyang University;

【机构】 南开大学元素有机化学国家重点实验室； 中国人民解放军309医院检疫检验科； Department of Chemistry,Institute of Natural Sciences,Hanyang University；

【摘要】 随着多药耐药(MDR)和广泛耐药(XDR)的结核分枝杆菌的出现,结核病又成为人类面临的重大疾病。近年来研究表明,乙酰乳酸合成酶(AHAS)可以作为抗结核(TB)药物的新靶点~1。我们同源蛋白模建了TB-AHAS的结构,经过虚拟筛选,发现了一类喹唑啉酮酸酯类化合物具有较好的抗结核活性~2。据此设计合成了20余个新结构的取代苯甲酸喹唑啉酮酸酯类化合物,不仅具有较好的TB-AHAS抑制活性,也具有较高的抗结核菌活性,对MDR和XDR结核菌都有明显效果~3。更多还原

【Abstract】 Mycobacterium tuberculosis(MTB) infection has become an increasing health threat due to the worldwide emergence of multidrug-resistant MTB(MDR-MTB) and extensively drug-resistant MTB(XDR-MTB).Recent study showed that acetohydroxyacid synthase(AHAS,E.C.2.2.1.6) could be considered as a novel target for anti-MTB agents~1.Some quinazolinone benzoates were discovered to have anti-MTB activity via virtual screening of AHAS binding site~2.Based on this,we designed and synthesized more than twenty substituted quinazolinone benzoates and evaluated their biological activity.These compounds not only showed good inhibition against MTB-AHAS,but also exhibited potent anti-tuberculosis activity,including MDR and XDR tuberculosis strains~3.更多还原