Abstract
In this report we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.
Keywords
neglected disease, Trypanosoma brucei, target repurposing, phosphodiesterase inhibitors, TbrPDEB1, PDE5, tadalafil
Subject Categories
Parasitic diseases - Treatment, Phosphodiesterases - Inhibitors
Disciplines
Parasitic Diseases | Pharmaceutics and Drug Design
Publisher
Elsevier Ltd.
Publication Date
2-9-2012
Rights Information
Copyright 2012
Rights Holder
Elsevier Ltd.
Recommended Citation
Ochiana, Stefan O.; Gustafson, Alden; Bland, Nicholas D.; Wang, Cuihua; Russo, Michael J.; Campbell, Robert K.; and Pollastri, Michael P., "Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs" (2012). Chemistry and Chemical Biology Faculty Publications. Paper 4.
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Notes
NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. The definitive version was published in Bioorganic & Medicinal Chemistry Letters (2012), DOI:10.1016/j.bmcl.2012.01.118