Cinnamyl hydroxamic acids: synthesis and anti-ureolytic properties

Urease is a nickel metalloenzyme responsible for the hydrolysis of urea to ammonia and carbamic acid. This enzyme is present in plants, bacteria and fungi. In human health, the activity of ureases is an important virulence factor in infections caused by ureolytic pathogens, since urea is the major nitrogenous metabolic product in humans. The ureolytic activity also impacts agricultural productivity, considering that urea is the main nitrogen fertilizer used worldwide. The negative effects of urease activity and the absence of safe and effective inhibitors motivate the development of new urease inhibitors. In this context, hydroxamic acids are an important class of compounds to be investigated, given that acetohydroxamic acid (AHA) has well-established inhibitory properties. In this work, eight cinnamyl hydroxamic acids were synthesized and had their urease inhibitory activities evaluated. The hydroxamic acids were obtained in 47-90% yields and preliminary tests showed inhibitory activities 10 times higher than to AHA.