Nocentini Alessio, Cadoni Roberta, Dumy Pascal, Supuran Claudiu T, Winum Jean-Yves
a Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, ENSCM, Université de Montpellier , Montpellier Cedex , France.
b NEUROFARBA Department, Section of Pharmaceutical and Nutraceutical Sciences , University of Florence, Polo Scientifico , Firenze , Italy.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):286-289. doi: 10.1080/14756366.2017.1414808.
A series of 6-substituted ureido- and thioureido-benzoxaboroles were investigated as inhibitors of carbonic anhydrases from Trypanosoma cruzi (TcCA), and Leishmania donovani chagasi (LdcCA). Both enzymes were inhibited by benzoxaboroles in the micromolar range. Preferential inhibitory potency against the β-CA LdcCA versus the α-CA TcCA was observed with submicromolar inhibitory activities. Some derivatives displayed excellent inhibitory and selectivity profile over the ubiquitous and physiological relevant human off-target hCA II. This study provides a convincing opportunity to study benzoxaborole scaffold for the design of antiprotozoan potential drugs targeting the pathogen's carbonic anhydrases.
研究了一系列6-取代的脲基和硫脲基苯并硼氧六环作为克氏锥虫（TcCA）和杜氏利什曼原虫恰加斯亚种（LdcCA）碳酸酐酶抑制剂的情况。两种酶均被微摩尔范围内的苯并硼氧六环抑制。观察到对β-碳酸酐酶LdcCA相对于α-碳酸酐酶TcCA具有优先抑制效力，且具有亚微摩尔抑制活性。一些衍生物对普遍存在且与生理相关的人类脱靶hCA II表现出优异的抑制和选择性特征。这项研究为研究苯并硼氧六环支架以设计针对病原体碳酸酐酶的抗原生动物潜在药物提供了一个有说服力的机会。
