In silico and in vitro evaluation of the urease interaction activity of naturally occurring catechol derived compounds

Urease plays a fundamental role in the pathogenicity of Gram-negative bacteria and in the biogeochemical nitrogen cycle. Interaction with urease may provide a better understanding of microbial pathogenicity, as well as serve as a promising strategy to reduce ureolytic activity. Since catechol is a urease inhibitor, substances containing this moiety, such as catecholamines, are natural candidates for interacting with urease. In this context, this work aimed to evaluate the in silico and in vitro interaction of dopamine, noradrenaline, and adrenaline with Canavalia ensiformis urease. Dopamine, noradrenaline, and adrenaline inhibited urease activity in a concentration-dependent manner, and the catechol presented a constant inhibition. Tyramine did not inhibit urease, highlighting that the catechol ring is essential. Classical kinetic studies have demonstrated that the catecholamines presented non-competitive inhibition. Molecular absorption spectroscopy and cyclic voltammetry clearly demonstrate the interactions between catecholamines and urease, with significant differences in the urease absorption spectrum and redox alterations in the voltammogram of the catecholamines. The dissociation constant (Kd) values for dopamine, adrenaline, noradrenaline, and catechol are respectively 7.09, 0.09, 3.71, and 0.01 µM. Tyramine presented the highest Kd (17.38), further evidencing the necessity of the possibly related nickel ion present in the urease active site, as confirmed by the in silico studies. Taken together, these data report for the first time catecholamines as inhibitors of urease with potential applications in several biological systems.