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.
neglected disease, Trypanosoma brucei, target repurposing, phosphodiesterase inhibitors, TbrPDEB1, PDE5, tadalafil
Parasitic diseases - Treatment, Phosphodiesterases - Inhibitors
Parasitic Diseases | Pharmaceutics and Drug Design
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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