Inhibition of trypanothione reductase by substrate analogues.
Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K(i) values ranging from 30 to 91 microM.
Garrard
E A
EA
Department of Chemistry, Carleton College, Northfield, Minnesota 55057, USA.
Borman
E C
EC
Cook
B N
BN
Pike
E J
EJ
Alberg
D G
DG
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005980:Glutathione Reductase / Q000737:chemistry; D007202:Indicators and Reagents; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009249:NADP / Q000737:chemistry; D013379:Substrate Specificity; D014345:Trypanosoma / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009249:NADP; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase