具有抗结核活性的新型AHAS抑制剂
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- 英文论文题名：Novel AHAS inhibitors with anti-tuberculosis activity
- 论文作者：卢伟 ; 王迪 ; 崔长军 ; 董梅 ; Moon-Young Yoon ; 王建国
- 英文论文作者：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
- 年：2016
- 作者机构：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;
- 论文关键词：乙酰乳酸合成酶 ; 虚拟筛选 ; 抗结核活性 ; 取代苯甲酸喹唑啉酮酸酯
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十五分会：化学信息学与化学计量学
- 语种：中文
- 分类号：TQ460.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十五分会 ; 化学信息学与化学计量学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：199k
- 原文格式：D
- 会议级别：全国
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。
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.
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.
引文
[1]Grandoni,J.A.;Marta,P.T.;Schloss,J.V.J.Antimicrob.Chemother.1998,42:475.
[2]Wang,D.;Zhu,X.;Cui,C;Dong,M.;Jiang,H.;Li,Z.;Liu,Z.;Zhu,W.;Wang,J.G.J.Chem.Inf.Model.2013,53:343.
[3]Lu,W.;Baig,I.A.;Sun,H.J.;Cui,C.J.;Guo,R.;Jung,I.P.;Wang,D.;Dong,M.;Yoon,M.Y.;Wang,J.G.Eur.J.Med.Chem.2015,94:298
[2]Wang,D.;Zhu,X.;Cui,C;Dong,M.;Jiang,H.;Li,Z.;Liu,Z.;Zhu,W.;Wang,J.G.J.Chem.Inf.Model.2013,53:343.
[3]Lu,W.;Baig,I.A.;Sun,H.J.;Cui,C.J.;Guo,R.;Jung,I.P.;Wang,D.;Dong,M.;Yoon,M.Y.;Wang,J.G.Eur.J.Med.Chem.2015,94:298