Adenosine/guanosine preferring nucleoside ribohydrolase is a distinct, druggable antitrichomonal target

作者：Beck Sierra; Muellers Samantha N; Benzie Annie Laurie; Parkin David W; Stockman Brian J^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(22): 5036-5039.

DOI：10.1016/j.bmcl.2015.10.030

• Flavonoids
• NIH Clinical Compound Collection
• NMR
• Nucleoside ribohydrolase
• Trichomonas vaginalis

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 mu M 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.

• 出版日期2015-11-15