Identification of proton-pump inhibitor drugs that inhibit Trichomonas vaginalis uridine nucleoside ribohydrolase.
Trichomonas vaginalis continues to be a major health problem with drug-resistant strains increasing in prevalence. Novel antitrichomonal agents that are mechanistically distinct from current therapies are needed. The NIH Clinical Compound Collection was screened to find inhibitors of the uridine ribohydrolase enzyme required by the parasite to scavenge uracil for its growth. The proton-pump inhibitors omeprazole, pantoprazole, and rabeprazole were identified as inhibitors of this enzyme, with IC50 values ranging from 0.3 to 14.5 μM. This suggests a molecular mechanism for the in vitro antitrichomonal activity of these proton-pump inhibitors, and may provide important insights toward structure-based drug design.
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
Tara A
TA
Shea
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
Paola J
PJ
Burburan
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
Vivian N
VN
Matubia
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
Sandy S
SS
Ramcharan
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
Irving
I
Rosario
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States.
David W
DW
Parkin
Department of Chemistry, Adelphi University, 1 South Avenue, Garden City, NY 11530, United States. Electronic address: bstockman@adelphi.edu.
Brian J
BJ
Stockman
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009853:Omeprazole / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D064750:Rabeprazole / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000201:enzymology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D000077402:Pantoprazole; D009699:N-Glycosyl Hydrolases; C096466:inosine-uridine hydrolase; D009853:Omeprazole
NIH Clinical Compound Collection; NMR; Proton-pump inhibitors; Trichomonas vaginalis; Uridine ribohydrolase