Next Article in Journal
Antifungal Activity of Oleuropein against Candida albicans—The In Vitro Study
Previous Article in Journal
Ribosome-Inactivating Proteins from Plants: A Historical Overview
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(12), 1628;

Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans

Departamento de Ciencias Químico-Biológicas, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chihuahua 32310, Mexico
These two authors contribute equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: James W. Gauld
Received: 8 October 2016 / Revised: 18 November 2016 / Accepted: 21 November 2016 / Published: 26 November 2016
(This article belongs to the Section Theoretical Chemistry)
Full-Text   |   PDF [3167 KB, uploaded 28 November 2016]   |  


Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2′-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a “hinge” located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity. View Full-Text
Keywords: urease; inhibition; disulfiram urease; inhibition; disulfiram

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Díaz-Sánchez, Á.G.; Alvarez-Parrilla, E.; Martínez-Martínez, A.; Aguirre-Reyes, L.; Orozpe-Olvera, J.A.; Ramos-Soto, M.A.; Núñez-Gastélum, J.A.; Alvarado-Tenorio, B.; de la Rosa, L.A. Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans. Molecules 2016, 21, 1628.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top