Ethacrynic acid as a lead structure for the development of potent urease inhibitors
Ethacrynic acid and a series of its analogues were synthesized and subsequently evaluated for their inhibitory effect on jack bean urease. Ethacrynic acid showed, even at low concentrations, very potent inhibitory activity against the enzyme. For ethacrynic acid, the inhibition potential increased with increasing preincubation time of ethacrynic acid and enzyme, whereas for some other compounds a higher preincubation time lead to a significant reduction of their activity. We could demonstrate that the alpha,beta-unsaturated carbonyl unit of our compounds is mandatory to inhibit the enzyme, possibly due to its ability to bind to cysteine residues in the active site of the jack bean urease. (C) 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Link to Published Version
Janser, I., Vortolomei, C. M., Meka, R. K., Walsh, C. A., & Janser, R. F. J. (2013). Ethacrynic acid as a lead structure for the development of potent urease inhibitors. Comptes Rendus Chimie, 16(7), 660–664. doi:10.1016/j.crci.2013.03.020