1. The 3D pharmacophore modeling to explore new antischistosomal agents among US FDA approved drugs.
- Author
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Dobrachinski L, Ferreira LL, Cirino ME, Andrade-de-Siqueira AI, Mafud AC, Mascarenhas YP, Andricopulo AD, and de Moraes J
- Subjects
- Animals, Mice, United States, Drug Approval, Schistosomicides pharmacology, Schistosomicides chemistry, Schistosomicides therapeutic use, Schistosomiasis mansoni drug therapy, Models, Molecular, Humans, Pharmacophore, Schistosoma mansoni drug effects, United States Food and Drug Administration
- 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% (EC
50 ) 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.- Published
- 2024
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