Inhibiting effects of spermidine derivatives on Trypanosoma cruzi trypanothione reductase.
Trypanothione reductase is a vital component of the antioxidant defenses of trypanosomes. This enzyme reduces trypanothione, a spermidine-glutathione conjugate. The inhibitory effects of several spermidine derivatives on the reduction of trypanothione by Trypanosoma cruzi trypanothione reductase were assessed. Spermidine derivatives containing hydrophobic aromatic substituents were found to be competitive inhibitors of trypanothione reductase. N4-acylated spermidine derivatives were less effective inhibitors than the corresponding N4-alkylated derivatives. The most effective compounds studied were N1, N8-bis(2-naphthylmethyl)spermidine and N4-(2-naphthylmethyl)spermidine, with Ki values of 9.5 and 108 microM, respectively.
O'Sullivan
M C
MC
Department of Chemistry, Indiana State University, Terre Haute 47809, USA.
Dalrymple
D M
DM
Zhou
Q
Q
D000818:Animals; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D013095:Spermidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000201:enzymology*
D004791:Enzyme Inhibitors; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D013095:Spermidine