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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Current Frontiers

Recent Efforts in the Discovery of Urease Inhibitor Identifications

Author(s): Wan-Qing Song, Mei-Ling Liu, Su-Ya Li and Zhu-Ping Xiao*

Volume 22, Issue 2, 2022

Published on: 10 December, 2021

Page: [95 - 107] Pages: 13

DOI: 10.2174/1568026621666211129095441

Price: $65

Abstract

Urease is an attractive drug target for designing anti-infective agents against pathogens such as Helicobacter pylori, Proteus mirabilis, and Ureaplasma urealyticum. In the past century, hundreds of medicinal chemists focused their efforts on explorations of urease inhibitors. Despite the FDA’s approval of acetohydroxamic acid as a urease inhibitor for the treatment of struvite nephrolithiasis and the widespread use of N-(n-butyl)thiophosphoric triamide as a soil urease inhibitor as nitrogen fertilizer synergists in agriculture, urease inhibitors with high potency and safety are urgently needed. Exploration of novel urease inhibitors has therefore become a hot research topic recently. Herein, inhibitors identified worldwide from 2016 to 2021 have been reviewed. They structurally belong to more than 20 classes of compounds such as urea/thioure analogues, hydroxamic acids, sulfonamides, metal complexes, and triazoles. Some inhibitors showed excellent potency with IC50 values lower than 10 nM, having 10000-fold higher potency than the positive control thiourea.

Keywords: Urease, Virulence factor, Urease inhibitor, Naturally occurring inhibitor, Non-covalent inhibitor, Covalent inhibitor.

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