Inhibition of trypanothione reductase by substrate analogues

Elizabeth A. Garrard; Emily C. Borman; Brian N. Cook; Emily J. Pike; David G. Alberg

doi:10.1021/ol0065423

Inhibition of trypanothione reductase by substrate analogues

Elizabeth A. Garrard, Emily C. Borman, Brian N. Cook, Emily J. Pike, David G. Alberg

General Pediatrics and Adolescent Health

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

(matrix presented) Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K_i values ranging from 30 to 91 μM.

Original language	English (US)
Pages (from-to)	3639-3642
Number of pages	4
Journal	Organic Letters
Volume	2
Issue number	23
DOIs	https://doi.org/10.1021/ol0065423
State	Published - Nov 16 2000

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title = "Inhibition of trypanothione reductase by substrate analogues",

abstract = "(matrix presented) Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with Ki values ranging from 30 to 91 μM.",

author = "Garrard, {Elizabeth A.} and Borman, {Emily C.} and Cook, {Brian N.} and Pike, {Emily J.} and Alberg, {David G.}",

year = "2000",

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doi = "10.1021/ol0065423",

language = "English (US)",

volume = "2",

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journal = "Organic Letters",

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T1 - Inhibition of trypanothione reductase by substrate analogues

AU - Garrard, Elizabeth A.

AU - Borman, Emily C.

AU - Cook, Brian N.

AU - Pike, Emily J.

AU - Alberg, David G.

PY - 2000/11/16

Y1 - 2000/11/16

N2 - (matrix presented) Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with Ki values ranging from 30 to 91 μM.

AB - (matrix presented) Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with Ki values ranging from 30 to 91 μM.

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SP - 3639

EP - 3642

JO - Organic Letters

JF - Organic Letters

IS - 23

ER -

Inhibition of trypanothione reductase by substrate analogues

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