Triosephosphate isomerase as a therapeutic target against trichomoniasis

• Published in: Molecular and biochemical parasitology 2021-11, Vol.246, p.111413-111413, Article 111413
• Main Authors: Benítez-Cardoza, Claudia G., Brieba, Luis G., Arroyo, Rossana, Rojo-Domínguez, Arturo, Vique-Sánchez, José L.
• Format: Article
• Language: English
• Subjects: Docking; Drug development; Humans; Metronidazole - pharmacology; Molecular Docking Simulation; Sexual transmitted diseases; Trichomonas Infections - drug therapy; Trichomonas Infections - parasitology; Trichomonas vaginalis; Trichomonas vaginalis - genetics; Triose-Phosphate Isomerase - genetics; Triosephosphate isomerase
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/j.molbiopara.2021.111413

•We screened a library of ∼500,000 compounds in silico, to identify selective compounds against TvTIM.•We identified the compound: (3,3′-{[4-(4-morpholinyl)phenyl]methylene}bis(4-hydroxy-2H-chromen-2-one) (A4) as potential drug.•We determined an IC50 of 47 μM of the A4 compound, with favorable toxicity results (in theoretical and experimental assays).•This finding represents a promising alternative to fight trichomoniasis. Trichomoniasis is the most common non-viral sexually transmitted infection, caused by the protozoan parasite Trichomonas vaginalis, affecting millions of people worldwide. The main treatment against trichomoniasis is metronidazole and other nitroimidazole derivatives, but up to twenty percent of clinical cases of trichomoniasis are resistant to these drugs. In this study, we used high-performance virtual screening to search for molecules that specifically bind to the protein, triosephosphate isomerase from T. vaginalis (TvTIM). By in silico molecular docking analysis, we selected six compounds from a chemical library of almost 500,000 compounds. While none of the six inhibited the enzymatic activity of recombinant triosephosphate isomerase isoforms, one compound (A4; 3,3′-{[4-(4-morpholinyl)phenyl]methylene}bis(4- hydroxy-2H-chromen-2-one) altered their fluorescence emission spectra, suggesting that this chemical might interfere in an important non-glycolytic function of TvTIM. In vitro assays demonstrate that A4 is not cytotoxic but does have trichomonacidal impact on T. vaginalis cultures. With these results, we propose this compound as a potential drug with a new therapeutic target against Trichomonas vaginalis.