Chemistry Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Chemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):59-64. doi: 10.1080/14756366.2019.1681987.
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.
对抗抗菌药物耐药性的一个主要策略是确定具有替代作用机制的新型治疗靶标和抗感染药物。已经证明抑制病原体（细菌、真菌和原生动物）中的金属酶碳酸酐酶（CA，EC 4.2.1.1）会导致微生物生长和毒力受损。由于膦酰胺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任何基于磷的锌结合基团对β 类 CA，因此本文报道了针对致病细菌、真菌和原生动物的β-CA 的抑制研究。我们的数据表明，膦酰胺类化合物是对β 类同工酶具有最佳选择性的 CAI 之一，使它们成为开发新型抗感染药物的有前途的先导化合物。
