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Multitask learning-driven identification of novel antitrypanosomal compounds.
Lemos, Jade Milhomem; Brito da Silva, Meryck Felipe; Dos Santos Carvalho, Alexandra Maria; Vicente Gil, Henric Pietro; Fiaia Costa, Vinícius Alexandre; Andrade, Carolina Horta; Braga, Rodolpho Campos; Grellier, Philippe; Muratov, Eugene N; Charneau, Sébastien; Moreira-Filho, José Teófilo; Dourado Bastos, Izabela Marques; Neves, Bruno Junior.
Afiliación
  • Lemos JM; LabChem - Laboratory of Cheminformatics, Faculty of Pharmacy, Federal University of Goiás, Goiânia,74605-170, GO, Brazil.
  • Brito da Silva MF; LabChem - Laboratory of Cheminformatics, Faculty of Pharmacy, Federal University of Goiás, Goiânia,74605-170, GO, Brazil.
  • Dos Santos Carvalho AM; Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, 70910-900, DF, Brazil.
  • Vicente Gil HP; LabChem - Laboratory of Cheminformatics, Faculty of Pharmacy, Federal University of Goiás, Goiânia,74605-170, GO, Brazil.
  • Fiaia Costa VA; LabChem - Laboratory of Cheminformatics, Faculty of Pharmacy, Federal University of Goiás, Goiânia,74605-170, GO, Brazil.
  • Andrade CH; LabMol - Laboratory for Molecular Modeling & Drug Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, 74605-170, GO, Brazil.
  • Braga RC; InsilicAll Ltda, Av. Eng. Luis Carlos Berrini,1748 - Itaim Bibi, 04571-010, Sao Paulo, SP, Brazil.
  • Grellier P; UMR 7245 Molécules de Communication et Adaptation des Micro-organismes, Muséum National d'Histoire Naturelle, Équipe Parasites et Protistes Libres, Paris, 0575231, France.
  • Muratov EN; Laboratory for Molecular Modeling, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, 27599, NC, USA.
  • Charneau S; Department of Pharmaceutical Sciences, Federal University of Paraiba, Joao Pessoa, 58059-900, PB, Brazil.
  • Moreira-Filho JT; Department of Cell Biology, Laboratory of Biochemistry & Protein Chemistry, Institute of Biological Sciences, University of Brasilia, Brasilia, 70910-900, DF, Brazil.
  • Dourado Bastos IM; LabMol - Laboratory for Molecular Modeling & Drug Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, 74605-170, GO, Brazil.
  • Neves BJ; Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, 70910-900, DF, Brazil.
Future Med Chem ; 15(16): 1449-1467, 2023 08.
Article en En | MEDLINE | ID: mdl-37701989
Background: Chagas disease and human African trypanosomiasis cause substantial death and morbidity, particularly in low- and middle-income countries, making the need for novel drugs urgent. Methodology & results: Therefore, an explainable multitask pipeline to profile the activity of compounds against three trypanosomes (Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Trypanosoma cruzi) were created. These models successfully discovered four new experimental hits (LC-3, LC-4, LC-6 and LC-15). Among them, LC-6 showed promising results, with IC50 values ranging 0.01-0.072 µM and selectivity indices >10,000. Conclusion: These results demonstrate that the multitask protocol offers predictivity and interpretability in the virtual screening of new antitrypanosomal compounds and has the potential to improve hit rates in Chagas and human African trypanosomiasis projects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tripanocidas / Trypanosoma brucei brucei / Trypanosoma cruzi / Tripanosomiasis Africana / Enfermedad de Chagas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Future Med Chem Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tripanocidas / Trypanosoma brucei brucei / Trypanosoma cruzi / Tripanosomiasis Africana / Enfermedad de Chagas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Future Med Chem Año: 2023 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido