title: S-Adenosylhomocysteine hydrolase of the protozoan parasite Trichomonas vaginalis: potent inhibitory activity of 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine.
abstract: In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 μM compared to 0.72 μM for metronidazole.
authors.affiliation: Department of Biological Sciences, University of the Pacific, Stockton, CA 95211, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Shokar
authors.forename: Aaron
authors.initials: A
authors.lastname: Au
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: An
authors.forename: Elsie
authors.initials: E
authors.lastname: Tong
authors.forename: Gabriel
authors.initials: G
authors.lastname: Garza
authors.forename: Jessica
authors.initials: J
authors.lastname: Zayas
authors.forename: Stanislaw F
authors.initials: SF
authors.lastname: Wnuk
authors.forename: Kirkwood M
authors.initials: KM
authors.lastname: Land
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008795:Metronidazole / Q000494:pharmacology; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000254:growth & development; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D008795:Metronidazole; D043383:Adenosylhomocysteinase; D000241:Adenosine; D014529:Uridine