TY - JOUR
T1 - Chinifur, a Selective Inhibitor and "Subversive Substrate" for Trypanosoma congolense Trypanothione Reductase
AU - Cenas, Narimantas
AU - Bironaite, Daiva
AU - Dickancaite, Egle
AU - Anusevicius, Zilvinas
AU - Sarlauskas, Jonas
AU - Blanchard, John S.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1994.2448
DO - 10.1006/bbrc.1994.2448
M3 - Article
C2 - 7945363
AN - SCOPUS:0028077833
SN - 0006-291X
VL - 204
SP - 224
EP - 229
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -