Druggability of the guanosine/adenosine/cytidine nucleoside hydrolase from Trichomonas vaginalis

• DOI: 10.1111/cbdd.13341
• Publication Date: 2018-05-29T06:16:12Z
• Authors: Rayyan Alam; Allen T. Barbarovich; Wagma Caravan; Mirna Ismail; Angela Barskaya; David W. Parkin; Brian J. Stockman
• Keywords: Druggability; Cytidine; Nucleoside analogue; Nucleotidase

Trichomonas vaginalis infects approximately 300 million people worldwide annually. Infected individuals have a higher susceptibility to more serious conditions such as cervical and prostate cancer. The parasite has developed increasing resistance current drug therapies, with an estimated 5% of clinical cases resulting from resistant strains, creating the need for new therapeutic strategies novel mechanisms action. Nucleoside salvage pathway enzymes represent targets these pathways are essential parasite's survival. guanosine/adenosine/cytidine nucleoside hydrolase ( GACNH ) may be particularly important its expression is upregulated under glucose‐limiting mimicking those that occur during infection establishment. was screened against NIH Clinical Collection explore druggability. Seven compounds were identified IC 50 values <20 μM. Extensive overlap found between inhibitors adenosine/guanosine AGNH ), but no uridine hydrolase. guanosine analog ribavirin only compound specific . Compounds inhibit both purine prove critical given role appears play in early stages infection.