ABSTRACT
Aim: To identify potential antischistosomal agents through 3D pharmacophore-based virtual screening of US FDA approved drugs.Materials & methods: A comprehensive virtual screening was conducted on a dataset of 10,000 FDA approved drugs, employing praziquantel as a template. Promising candidates were selected and assessed for their impact on Schistosoma mansoni viability in vitro and in vivo using S. mansoni infected mice.Results & conclusion: Among the selected drugs, betamethasone and doxazosin demonstrated in vitro efficacy, with effective concentration 50% (EC50) values ranging from 35 to 60 µM. In vivo studies revealed significant (>50%) reductions in worm burden for both drugs. These findings suggest that betamethasone and doxazosin hold promise for repurposing in treating schistosomiasis. Additionally, the study showcases a useful approach for identifying new antischistosomal drugs.
Discovering new treatments for #schistosomiasis is crucial [Formula: see text]. Our study used virtual screening to identify potential antischistosomal drugs from US FDA approved compounds [Formula: see text]. Promising results in vitro and in vivo. [Formula: see text] #drugdiscovery #tropicaldiseases.
Subject(s)
Schistosoma mansoni , United States Food and Drug Administration , Animals , Mice , Schistosoma mansoni/drug effects , United States , Drug Approval , Schistosomicides/pharmacology , Schistosomicides/chemistry , Schistosomicides/therapeutic use , Schistosomiasis mansoni/drug therapy , Models, Molecular , Humans , PharmacophoreABSTRACT
Background: Chagas disease is a neglected tropical disease that affects millions of people worldwide and for which no effective treatment is available. Materials & methods: 17 chalcones were synthesized, for which the inhibition of cruzain and trypanocidal activity were investigated. Results: Chalcone C8 showed the highest cruzain inhibitory (IC50 = 0.536 µm) and trypanocidal activity (IC50 = 0.990 µm). Molecular docking studies showed interactions involving Asp161 and the thiophen group interacting with the S2 subsite. Furthermore, quantitative structure-activity relationship (q2 = 0.786; r2 = 0.953) and density functional theory studies were carried out, and a correlation between the lowest unoccupied molecular orbital surface and trypanocidal activity was observed. Conclusion: These results demonstrate that these chalcones are worthwhile hits to be further optimized in Chagas disease drug discovery programs.