title: Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs.
abstract: In this Letter 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.
authors.affiliation: Northeastern University Department of Chemistry and Chemical Biology, 417 Egan Research Center, 360 Huntington Avenue, Boston, MA 02115, United States.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Ochiana
authors.forename: Alden
authors.initials: A
authors.lastname: Gustafson
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Bland
authors.forename: Cuihua
authors.initials: C
authors.lastname: Wang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Russo
authors.forename: Robert K
authors.initials: RK
authors.lastname: Campbell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pollastri
mesh_terms: D000818:Animals; D001681:Biological Assay; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D058986:Phosphodiesterase 5 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012996:Solutions; D013329:Structure-Activity Relationship; D000068581:Tadalafil; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D014346:Trypanosoma brucei brucei / Q000201:enzymology*
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D015800:Protozoan Proteins; D012996:Solutions; D014344:Trypanocidal Agents; D000068581:Tadalafil; D010727:Phosphoric Diester Hydrolases