Biginelli adducts: Ionic-liquid assisted synthesis and their effects on the ureolytic activity of ureases

Urease is a metalloenzyme present in bacteria, plants, and soils. Its catalytic action on urea hydrolysis brings relevant impairment to agriculture since its ureolytic activity hydrolyses the main used nitrogen fertilizer, the urea. To human health, urease has been recognized as an essential virulence factor for several human pathogens, such as Helicobacter Pylori and Cryptococcus neoformans. [1-3] In this study, a series of Biginelli adducts (BAs) were synthesized (26 examples) and their antiureolytic activity, as well as their mechanism for the antiureolytic action, were evaluated against purified urease from jack beans, the typical model used in antiureolytic studies. Kinetic studies demonstrated that the most promising BAs are GEQOB5-S (36% of inhibition) and GEQOB7-S (48% of inhibition) presenting binding constant values of logKb 4,28 M-1 and 5.95 M-1, respectively. The results disclosed that the synthesized Biginelli adducts are efficient inhibitors such as hydroxyurea, the positive control used in in vitro assays.