具有体外抗疟活性的甘油醛-3-磷酸脱氢酶共价抑制剂
Covalent Inhibitors of Glyceraldehyde 3-Phosphate Dehydrogenase with Antimalarial Activity in Vitro.
作者信息
Cullia Gregorio, Bruno Stefano, Parapini Silvia, Margiotta Marilena, Tamborini Lucia, Pinto Andrea, Galbiati Andrea, Mozzarelli Andrea, Persico Marco, Paladino Antonella, Fattorusso Caterina, Taramelli Donatella, Conti Paola
机构信息
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Area Parco delle Scienze 23A, 43124 Parma, Italy.
出版信息
ACS Med Chem Lett. 2019 Feb 20;10(4):590-595. doi: 10.1021/acsmedchemlett.8b00592. eCollection 2019 Apr 11.
Abstract
Covalent inhibitors of GAPDH characterized by a 3-bromoisoxazoline warhead were developed, and their mode of interaction with the target enzyme was interpreted by means of molecular modeling studies: some of them displayed a submicromolar antiplasmodial activity against both chloroquine sensitive and resistant strains of , with good selectivity indices.
摘要
开发了以3-溴异恶唑啉弹头为特征的甘油醛-3-磷酸脱氢酶（GAPDH）共价抑制剂，并通过分子模拟研究解释了它们与靶酶的相互作用模式：其中一些对氯喹敏感和耐药菌株均表现出亚微摩尔级的抗疟活性，且具有良好的选择性指数。
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