The 3D pharmacophore modeling to explore new antischistosomal agents among US FDA approved drugs.
DOBRACHINSKI, Leandro; FERREIRA, Leonardo Luiz Gomes; CIRINO, Maria Eduarda de; SIQUEIRA, Allan Igor Andrade de; MAFUD, Ana Carolina; MASCARENHAS, Yvonne Primerano; ANDRICOPULO, Adriano Defini; MORAES, Josué de.
DOBRACHINSKI, Leandro; FERREIRA, Leonardo Luiz Gomes; CIRINO, Maria Eduarda de; SIQUEIRA, Allan Igor Andrade de; MAFUD, Ana Carolina; MASCARENHAS, Yvonne Primerano; ANDRICOPULO, Adriano Defini; MORAES, Josué de.
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.
@article={003218883,author = {DOBRACHINSKI, Leandro; FERREIRA, Leonardo Luiz Gomes; CIRINO, Maria Eduarda de; SIQUEIRA, Allan Igor Andrade de; MAFUD, Ana Carolina; MASCARENHAS, Yvonne Primerano; ANDRICOPULO, Adriano Defini; MORAES, Josué de.},title={The 3D pharmacophore modeling to explore new antischistosomal agents among US FDA approved drugs},journal={Future Medicinal Chemistry},note={v. 16, n. 17, p. 1791-1799},year={2024}}