A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

Ureases are enzymes that hydrolyze urea into ammonium and carbon dioxide. They have received considerable attention due to their impacts on living organism health, since the urease activity in microorganisms, particularly in bacteria, are potential causes and/or factors contributing to the persistence of some pathogen infections. This review compiles examples of the most potent antiurease organic substances. Emphasis was given to systematic screening studies on the inhibitory activity of rationally designed series of compounds with the corresponding SAR considerations. Ureases of Canavalia ensiformis, the usual model in antiureolytic studies, are emphasized. Although the active site of this class of hydrolases is conserved among bacteria and vegetal ureases, the same is not observerd for allosteric site. Therefore, inhibitors acting by participating in interactions with the allosteric site are more susceptible to a potential lack of association among their inhibitory profile for different ureases. The information about the inhibitory activity of different classes of compounds can be usefull to guide the development of new urease inhibitors that may be used in future in small molecular therapy against pathogenic bacteria.