INHIBITING EFFECTS OF SPERMIDINE DERIVATIVES ON TRYPANOSOMA-CRUZI TRYPANOTHIONE REDUCTASE

Trypanothione reductase is a vital component of the antioxidant defens es of trypanosomes. This enzyme reduces trypanothione, a spermidine-gl utathione conjugate. The inhibitory effects of several spermidine deri vatives on the reduction of trypanothione by Trypanosoma cruzi trypano thione reductase were assessed. Spermidine derivatives containing hydr ophobic aromatic substituents were found to be competitive inhibitors of trypanothione reductase. N-4-acylated spermidine derivatives were l ess effective inhibitors than the corresponding N-4-alkylated derivati ves. The most effective compounds studied were N-1,N-8-bis(2-naphthylm ethyl)spermidine and N-4-(2-naphthylmethyl)spermidine, with K-i values of 9.5 and 108 mu M, respectively.