Catechol-based inhibitors of bacterial urease

Aikaterini Pagoni; Theohari Daliani; Katarzyna Macegoniuk; Stamatia Vassiliou; Łukasz Berlicki

doi:10.1016/j.bmcl.2019.02.032

Catechol-based inhibitors of bacterial urease

Bioorg Med Chem Lett. 2019 May 1;29(9):1085-1089. doi: 10.1016/j.bmcl.2019.02.032. Epub 2019 Feb 27.

Authors

Aikaterini Pagoni¹, Theohari Daliani¹, Katarzyna Macegoniuk², Stamatia Vassiliou³, Łukasz Berlicki⁴

Affiliations

¹ Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Zografou, 15701 Athens, Greece.
² Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
³ Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Zografou, 15701 Athens, Greece. Electronic address: svassiliou@chem.uoa.gr.
⁴ Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland. Electronic address: lukasz.berlicki@pwr.edu.pl.

PMID: 30850166
DOI: 10.1016/j.bmcl.2019.02.032

Abstract

Targeted covalent inhibitors of urease were developed on the basis of the catechol structure. Forty amide and ester derivatives of 3,4-dihydroxyphenylacetic acid, caffeic acid, ferulic acid and gallic acid were obtained and screened against Sporosarcinia pasteurii urease. The most active compound, namely propargyl ester of 3,4-dihydroxyphenylacetic acid exhibited IC₅₀ = 518 nM andk_inact/K_i = 1379 M^-1 s^-1. Inhibitory activity of this compound was better and toxicity lower than those obtained for the starting compound - catechol. The molecular modelling studies revealed a mode of binding consistent with structure-activity relationships.

Keywords: Cysteine; Irreversible inhibition; Nickel-dependent enzyme; Targeted covalent inhibitors; Urease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Catechols / chemistry
Catechols / pharmacology*
Enzyme Inhibitors / chemistry
Gene Expression Regulation, Bacterial / drug effects
Models, Molecular
Molecular Docking Simulation
Protein Conformation
Sporosarcina / enzymology*
Structure-Activity Relationship
Urease / antagonists & inhibitors*

Substances

Anti-Bacterial Agents
Catechols
Enzyme Inhibitors
Urease

Supplementary concepts

Sporosarcina pasteurii