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Melo-Filho, Cleber C.; Dantas, Rafael F.; Braga, Rodolpho C.; Neves, Bruno J.; Senger, Mario R.; Valente, Walter C.G.; Rezende-Neto, João M.; Chaves, Willian T.; Muratov, Eugene N.; Paveley, Ross A.; Furnham, Nicholas; Kamentsky, Lee; Carpenter, Anne E.; Silva-Junior, Floriano P.; Andrade, Carolina H. (2016)
Publisher: American Chemical Society
Languages: English
Types: Article
Subjects: Article
: Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents.
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    • 383(9936), 2253-64 (2014). Available from: http://www.ncbi.nlm.nih.gov/pubmed/24698483.
    • World Health Organization. Schistosomiasis. Fact sheet N°115. (2015).
    • Gryseels B. Schistosomiasis. Infect. Dis. Clin. North Am. [Internet]. 26(2), 383-97 (2012).
    • Available from: http://www.ncbi.nlm.nih.gov/pubmed/22632645.
    • 368(9541), 1106-18 (2006). Available from: http://www.ncbi.nlm.nih.gov/pubmed/16997665.
    • World Health Organization. Progress report 2001-2011 and strategic plan 2012-2020. Geneva, Switzerland.
    • Hagan P, Appleton CC, Coles GC, Kusel JR, Tchuem-Tchuenté L-A. Schistosomiasis control: keep taking the tablets. Trends Parasitol. 20(2), 92-97 (2004).
    • Loukas A, Bethony JM. New drugs for an ancient parasite. Nat. Med. [Internet]. 14(4), 365-7 (2008). Available from: http://www.ncbi.nlm.nih.gov/pubmed/18391931.
    • Wang W, Wang L, Liang Y-S. Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol. Res. [Internet]. 111(5), 1871-7 (2012). Available from: http://www.ncbi.nlm.nih.gov/pubmed/23052781.
    • Caffrey CR. Chemotherapy of schistosomiasis: present and future. Curr. Opin. Chem. Biol. 11(4), 433-9 (2007).
    • Molecules. 20(2), 1872-1903 (2015).
    • Nature [Internet]. 460(7253), 352-8 (2009). Available from: 12.
    • Braga RC, Andrade CH. Assessing the performance of 3D pharmacophore models in virtual screening: how good are they? Curr. Top. Med. Chem. 13(9), 1127-1138 (2013).
    • Hawkins PCD, Skillman AG, Warren GL, Ellingson BA, Stahl MT. Conformer generation with OMEGA: algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model. [Internet]. 50(4), 572-84 (2010). Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2859685&tool=pmcentrez&rendertyp 42.
    • Pratim Roy P, Paul S, Mitra I, Roy K. On two novel parameters for validation of predictive QSAR models. Molecules. 14(5), 1660-701 (2009).
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