Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug target for african sleeping sickness

Michael D Urbaniak; Jioji N Tabudravu; Aichi Msaki; Kathy Mansfield Matera; Ruth Brenk; Marcel Jaspars; Michael A J Ferguson

doi:10.1016/j.bmcl.2006.08.091

Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug target for african sleeping sickness

Bioorg Med Chem Lett. 2006 Nov 15;16(22):5744-7. doi: 10.1016/j.bmcl.2006.08.091. Epub 2006 Sep 7.

Authors

Michael D Urbaniak¹, Jioji N Tabudravu, Aichi Msaki, Kathy Mansfield Matera, Ruth Brenk, Marcel Jaspars, Michael A J Ferguson

Affiliation

¹ Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

PMID: 16962325
DOI: 10.1016/j.bmcl.2006.08.091

Abstract

Novel inhibitors of Trypanosoma brucei and mammalian UDP-Glc 4'-epimerase were identified by screening a small library of natural products and commercially available drug-like molecules. The inhibitors possess low micromolar potency against the T. brucei and human enzymes in vitro, display a degree of selectivity between the two enzymes, and are cytotoxic to cultured T. brucei and mammalian cells.

Publication types

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

MeSH terms

Animals
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Models, Chemical
Trypanocidal Agents / chemistry
Trypanocidal Agents / pharmacology*
Trypanocidal Agents / therapeutic use
Trypanosoma brucei brucei / drug effects*
Trypanosoma brucei brucei / growth & development
Trypanosomiasis, African / drug therapy*
UDPglucose 4-Epimerase / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Trypanocidal Agents
UDPglucose 4-Epimerase

Grants and funding

071463/Wellcome Trust/United Kingdom