Chinifur, a Selective Inhibitor and "Subversive Substrate" for Trypanosoma congolense Trypanothione Reductase

N. Cenas, D. Bironaite, E. Dickancaite, Z. Anusevicius, J. Sarlauskas, John S. Blanchard

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Nitrofurans with aromatic and heterocyclic substituents inhibit Trypanosoma congolense trypanothione reductase (TR) and yeast glutathione reductase (GR), acting as uncompetitive inhibitors vs. NADPH and noncompetitive or uncompetitive inhibitors vs. disulfide substrate. Many of these compounds inhibited trypanothione reductase more efficiently than glutathione reductase. Chinifur (2-{5′-nitro(furo-2′-yl)-ethene-1-yl}-4(N,N-diethylamino)-1- methyl-but-1-yl-arninocarbonyl-4-quinoline) was the most selective inhibitor of, and free radical-generating substrate for, trypanothione reductase (Ki = 4.5 μm, TN = 3 s-1, TN/Km = 3.2 × 104 M-1 s-1), only weakly inhibiting glutathione reductase (Ki = 100 μm). These findings point to the importance of hydrophobic interactions in the design of redox active heteroaromatic compounds acting as selective inhibitors of, and "subversive substrates" for, trypanothione reductase.

Original languageEnglish (US)
Pages (from-to)224-229
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume204
Issue number1
DOIs
StatePublished - Oct 15 1994

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Trypanosoma congolense
Glutathione Reductase
Substrates
Nitrofurans
NADP
Hydrophobic and Hydrophilic Interactions
Disulfides
Yeast
Oxidation-Reduction
Free Radicals
Yeasts
trypanothione reductase
chinifur

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Chinifur, a Selective Inhibitor and "Subversive Substrate" for Trypanosoma congolense Trypanothione Reductase. / Cenas, N.; Bironaite, D.; Dickancaite, E.; Anusevicius, Z.; Sarlauskas, J.; Blanchard, John S.

In: Biochemical and Biophysical Research Communications, Vol. 204, No. 1, 15.10.1994, p. 224-229.

Research output: Contribution to journalArticle

Cenas, N. ; Bironaite, D. ; Dickancaite, E. ; Anusevicius, Z. ; Sarlauskas, J. ; Blanchard, John S. / Chinifur, a Selective Inhibitor and "Subversive Substrate" for Trypanosoma congolense Trypanothione Reductase. In: Biochemical and Biophysical Research Communications. 1994 ; Vol. 204, No. 1. pp. 224-229.
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