title: Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).
abstract: Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease that affects 10,000 patients each year. Current treatments are sub-optimal, and the disease is fatal if not treated. Herein, we report our continuing efforts to repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target trypanosomal phosphodiesterase TbrPDEB1. We prepared a range of substituted heterocyclic replacements for the 4-amino-3,5-dichloro-pyridine headgroup of piclamilast, and found that these compounds exhibited weak inhibitory activity of TbrPDEB1.
authors.affiliation: Northeastern University, Department of Chemistry and Chemical Biology, 417 Egan Research Center, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Woodring
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Bland
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Ochiana
authors.forename: Robert K
authors.initials: RK
authors.lastname: Campbell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pollastri
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology
chemical_list: D001549:Benzamides; D002396:Catechols; D058988:Phosphodiesterase 4 Inhibitors; D015800:Protozoan Proteins; D011725:Pyridines; D014344:Trypanocidal Agents; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C581006:PDEB1 protein, Trypanosoma brucei; C034221:catechol; C087566:piclamilast
keywords: Drug discovery; Neglected Disease; Phosphodiesterases; Piclamilast; TbrPDEB1; TbrPDEB2; Trypanosoma brucei
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