Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group.
Glutathionylspermidine synthetase/amidase (GspS) is an essential enzyme in the biosynthesis and turnover of trypanothione and represents an attractive target for the design of selective anti-parasitic drugs. We synthesised a series of analogues of glutathione (L-gamma-Glu-L-Leu-Gly-X) where the glycine carboxylic acid group (X) has been substituted for other acidic groups such as tetrazole, hydroxamic acid, acylsulphonamide and boronic acid. The boronic acid appears the most promising lead compound (IC(50) of 17.2 microM).
Department of Medicinal Chemistry, University of Antwerp (UIA), Belgium.
Katie
K
Amssoms
Sandra L
SL
Oza
Esteban
E
Ravaschino
Abdellah
A
Yamani
Anne
A
Lambeir
Padinchare
P
Rajan
Gunther
G
Bal
Juan
J
Rodriguez
Alan H
AH
Fairlamb
Koen
K
Augustyns
Achiel
A
Haemers
D019732:Amide Synthases / Q000037:antagonists & inhibitors*; D002264:Carboxylic Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology*; D005998:Glycine / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D019732:Amide Synthases; C081536:glutathionylspermidine synthetase; D005978:Glutathione; D005998:Glycine