The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase

Josephine A. Czechowicz, April K. Wilhelm, Maroya D. Spalding, Anna M. Larson, Linnea K. Engel, David G. Alberg

Research output: Contribution to journalArticlepeer-review

Abstract

(Chemical Equation Presented) Trypanothione reductase (TR) catalyzes the NADPH-dependent reduction of trypanothione disulfide (1). TR plays a central role in the trypanosomatid parasite's defense against oxidative stress and has emerged as a promising target for antitrypanosomal drugs. We describe the synthesis and activity of dethiotrypanothione and analogues (2-4) as inhibitors of Trypanosoma cruzi TR. The syntheses of these macrocycles feature ring-closing olefin metathesis (RCM) reactions catalyzed by ruthenium catalyst 17. Derivative 4 is our most potent inhibitor with a Ki = 16 μM.

Original languageEnglish (US)
Pages (from-to)3689-3693
Number of pages5
JournalJournal of Organic Chemistry
Volume72
Issue number10
DOIs
StatePublished - May 11 2007
Externally publishedYes

Fingerprint

Dive into the research topics of 'The synthesis and inhibitory activity of dethiotrypanothione and analogues against trypanothione reductase'. Together they form a unique fingerprint.

Cite this