Discovery of Ligand-Efficient Scaffolds for the Design of Novel Trichomonas vaginalis Uridine Nucleoside Ribohydrolase Inhibitors Using Fragment Screening.

ABSTRACT: Trichomoniasis is caused by the parasitic protozoan Trichomonas vaginalis. The increasing prevalence of strains resistant to the current 5-nitroimidazole treatments creates the need for novel therapies. T. vaginalis cannot synthesize purine and pyrimidine rings and requires salvage pathway enzymes to obtain them from host nucleosides. The uridine nucleoside ribohydrolase was screened using an ¹⁹F NMR-based activity assay against a 2000-compound fragment diversity library. Several series of inhibitors were identified including scaffolds based on acetamides, cyclic ureas or ureas, pyridines, and pyrrolidines. A number of potent singleton compounds were identified, as well. Eighteen compounds with IC₅₀ values of 20 μM or lower were identified, including som

SUBMITTER: Auletta S 

PROVIDER: S-EPMC6777076 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature