title: Adenosine/guanosine preferring nucleoside ribohydrolase is a distinct, druggable antitrichomonal target.
abstract: Nucleoside salvage pathway enzymes used by Trichomonas vaginalis are distinct from the pathway involved in activation of existing 5-nitroimidazole drugs. They thus represent excellent targets for developing novel, mechanism-based antitrichomonal agents. The purine-specific adenosine/guanosine preferring ribohydrolase (AGNH) was screened against the NIH Clinical Collection to assess its druggability. Eight compounds, including five flavonoids, were identified with IC50 values ⩽10 μM and confirmed in counter screens run in the presence of detergent. The inhibitors are structurally distinct from inhibitors of the pyrimidine-specific uridine ribohydrolase (UNH) thus indicating that AGNH is a distinct, druggable target from UNH.
authors.affiliation: Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
authors.forename: Sierra
authors.initials: S
authors.lastname: Beck
authors.affiliation: Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: Muellers
authors.affiliation: Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
authors.forename: Annie Laurie
authors.initials: AL
authors.lastname: Benzie
authors.affiliation: Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
authors.forename: David W
authors.initials: DW
authors.lastname: Parkin
authors.affiliation: Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States. Electronic address: bstockman@adelphi.edu.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stockman
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D000994:Antitrichomonal Agents / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors*; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry; D013237:Stereoisomerism; D014246:Trichomonas vaginalis
chemical_list: D000994:Antitrichomonal Agents; D005419:Flavonoids; D054852:Small Molecule Libraries; C058394:2-chloro-N(6)cyclopentyladenosine; C023277:uridine nucleosidase; D011794:Quercetin; C003377:taxifolin; D009699:N-Glycosyl Hydrolases; C030681:purine nucleosidase; D000241:Adenosine
keywords: Flavonoids; NIH Clinical Compound Collection; NMR; Nucleoside ribohydrolase; Trichomonas vaginalis