Insights into the design of inhibitors of the urease enzyme – a major target for the treatment of Helicobacter pylori infections

(E-pub Abstract Ahead of Print)

Author(s): Ana Thereza Fiori-Duarte, Ricardo Pereira Rodrigues, Rodrigo Rezende Kitagawa, Daniel Fábio Kawano*.

Journal Name: Current Medicinal Chemistry

Become EABM
Become Reviewer

Abstract:

Expressed by a variety of plants, fungi and bacteria, the urease enzyme is directly associated with the virulence factor of many bacteria, including Helicobacter pylori, a gram-negative bacterium related with several gastrointestinal diseases and responsible for one of the most frequent bacterial infections throughout the world. The Helicobacter pylori urease (HPU) is a nickel-dependent metalloenzyme expressed in response to the environmental stress caused by the acidic pH of the stomach. The enzyme promotes the increase of gastric pH through acid neutralization by the products of urea hydrolysis, then critically contributing to the colonization and pathogenesis of the microorganism. At the same time, standard treatments for Helicobacter pylori infections have limitations such as the increasing bacterial resistance to the antibiotics used in the clinical practice. As a strategy for the development of novel treatments, urease inhibitors have proved to be promising, with a wide range of chemical compounds, including natural, synthetic and semisynthetic products to be researched and potentially developed as new drugs. In this context, this review highlights the advances in the field of HPU inhibition, presenting and discussing the basis for the research of new molecules aiming the identification of more efficient therapeutic entities.

Keywords: Helicobacter pylori, urease, drug discovery, peptic ulcer, gastritis, gastric adenocarcinoma.

Rights & PermissionsPrintExport Cite as


Article Details

(E-pub Abstract Ahead of Print)
DOI: 10.2174/0929867326666190301143549
Price: $95