Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug target for african sleeping sickness.
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.
Urbaniak
Michael D
MD
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Tabudravu
Jioji N
JN
Msaki
Aichi
A
Matera
Kathy Mansfield
KM
Brenk
Ruth
R
Jaspars
Marcel
M
Ferguson
Michael A J
MA
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D014534:UDPglucose 4-Epimerase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D014534:UDPglucose 4-Epimerase