A primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to produce an impairment of the microorganism growth and virulence. As phosphonamidates have been recently validated as human α-CA inhibitors (CAIs) and no phosphorus-based zinc-binding group have been assessed to date against β-class CAs, herein we report an inhibition study with this class of compounds against β-CAs from pathogenic bacteria, fungi, and protozoa. Our data suggest that phosphonamidates are among the CAIs with the best selectivity for β-class over human isozymes, making them interesting leads for the development of new anti-infectives.

中文翻译：

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膦酰胺是第一个磷基锌结合基序，可抑制细菌、真菌和原生动物的 β 类碳酸酐酶。


对抗抗菌素耐药性的主要策略是确定新的治疗靶点和具有替代作用机制的抗感染药物。抑制病原体（细菌、真菌和原生动物）的金属酶碳酸酐酶（CA、EC 4.2.1.1）会损害微生物的生长和毒力。由于氨基膦酸酯最近已被验证为人类 α-CA 抑制剂 (CAI)，并且迄今为止尚未评估磷基锌结合基团对 β 类 CA 的作用，因此我们在本文中报告了此类化合物对 β-CA 的抑制研究来自致病细菌、真菌和原生动物。我们的数据表明，与人类同工酶相比，氨基膦酸盐是对 β 类具有最佳选择性的 CAI 之一，这使得它们成为开发新型抗感染药物的有趣线索。