+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Inhibiting effects of spermidine derivatives on Trypanosoma cruzi trypanothione reductase



Inhibiting effects of spermidine derivatives on Trypanosoma cruzi trypanothione reductase



Journal of Enzyme Inhibition 11(2): 97-114



Trypanothione reductase is a vital component of the antioxidant defenses of trypanosomes. This enzyme reduces trypanothione, a spermidine-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 Ki values of 9.5 and 108 microM, respectively.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046408745

Download citation: RISBibTeXText

PMID: 9204399


Related references

Inhibiting Effects of Spermidine Derivatives on Trypanosoma Cruzz Trypanothione Reductase. Journal of Enzyme Inhibition and Medicinal Chemistry 11(2): 97-114, 1996

The inhibiting effects of N,N,N,N-tetra substituted polyamine derivatives on Trypanosoma cruzi trypanothione reductase. Abstracts of Papers American Chemical Society 223(1-2): CHED 685, 2002

New spermine and spermidine derivatives as potent inhibitors of Trypanosoma cruzi trypanothione reductase. Bioorganic and Medicinal Chemistry 5(7): 1249-1256, 1997

Design, synthesis and biological evaluation of new potent 5-nitrofuryl derivatives as anti-Trypanosoma cruzi agents. Studies of trypanothione binding site of trypanothione reductase as target for rational design. European Journal of Medicinal Chemistry 39(5): 421-431, 2004

N- substituted polyamine derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase. Abstracts of Papers American Chemical Society 225(1-2): CHED 362, 2003

Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity. European Journal of Medicinal Chemistry 141: 138-148, 2017

Novel polyamine derivatives as potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase. Bioorganic & Medicinal Chemistry Letters 5(17): 1957-1960, 1995

Rational design of nitrofuran derivatives: Synthesis and valuation as inhibitors of Trypanosoma cruzi trypanothione reductase. European Journal of Medicinal Chemistry 125: 1088-1097, 2016

The inhibiting effects of N- and N- substituted polyamine derivatives on trypanothione reductase and glutathione reductase. Abstracts of Papers American Chemical Society 223(1-2): CHED 686, 2002

Novel aryl β-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures. Journal of Biomolecular Structure and Dynamics 29(6): 702-716, 2012

A single enzyme catalyses formation of Trypanothione from glutathione and spermidine in Trypanosoma cruzi. Journal of Biological Chemistry 277(39): 35853-35861, 2002

Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure 7(1): 81-89, 1999

2- and 3-substituted 1,4-naphthoquinone derivatives as subversive substrates of trypanothione reductase and lipoamide dehydrogenase from Trypanosoma cruzi: synthesis and correlation between redox cycling activities and in vitro cytotoxicity. Journal of Medicinal Chemistry 44(4): 548-565, 2001

Synthesis and evaluation of 9,9-dimethylxanthene tricyclics against trypanothione reductase, Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani. Bioorganic and Medicinal Chemistry Letters 10(11): 1147-1150, 2000

Platinum complexes are irreversible inhibitors of Trypanosoma cruzi trypanothione reductase but not of human glutathione reductase. Journal of Medicinal Chemistry 43(25): 4812-4821, December 14, 2000