Inhibiting Effects of Spermidine Derivatives on Trypanosoma Cruzz Trypanothione Reductase

Abstract

Trypanothione reductase is a vital component of the antioxidant defenses of trypanosomes. This enzyme reduces trypanothione, a Ispermidine-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 K_i values of 9.5 and 108 μ;M, respectively.

Key Words: :

• Spermidine
• polyamine
• trypanothione reductase
• Trypanosoma cruzi
• Chagas disease