A series of 6-substituted benzoxaboroles were investigated as inhibitors of the β-class carbonic anhydrase from three pathogenic fungi (Cryptococcus neoformans, Candida glabrata, and Malassezia globosa). Independently from the nature of the substituents on the phenyl of the urea/thiourea group, all reported derivatives showed nanomolar inhibitory activities against Can2 and CgNce103 vs micromolar inhibition against MgCA. Selectivity over human CA I and CA II was noticed. The observed structure–activity relationship trends have been rationalized by modeling study of selected compounds into the active site of Can2 and MgCA. The present letter demonstrates that benzoxaborole chemotype may offer interesting opportunities for the inhibition of β-CA from pathogenic fungi and for the development of antifungal agents with a new mechanism of action.

中文翻译：

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苯并恶草硼烷作为致病真菌β-碳酸酐酶的有效抑制剂：活性和模型研究

研究了一系列6位取代的苯并x硼烷作为来自三种病原真菌（新隐球菌，光滑念珠菌和球形疟原虫）的β类碳酸酐酶的抑制剂。）。独立于脲/硫脲基团的苯基上的取代基的性质，所有报道的衍生物均显示出对Can2和CgNce103的纳摩尔抑制活性与对MgCA的微摩尔抑制相比。注意到对人CA I和CA II的选择性。通过对进入Can2和MgCA活性位点的所选化合物进行建模研究，已合理化了观察到的构效关系趋势。本信证明苯并氧杂硼烷的化学型可能为抑制致病性真菌中的β-CA和开发具有新作用机制的抗真菌剂提供有趣的机会。