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Identification of novel potential cyclooxygenase-2 inhibitors using ligand- and structure-based virtual screening approaches.
Cruz, Josiane V; Giuliatti, Silvana; Alves, Levy B; Silva, Raí C; Ferreira, Elenilze F B; Kimani, Njogu M; Silva, Carlos H T P; Souza, João S N de; Espejo-Román, José M; Santos, Cleydson B R.
Afiliación
  • Cruz JV; Graduate Program in Pharmaceutical Innovation, Department of Biological Sciences and Health, Federal University of Amapá, Macapá, Brazil.
  • Giuliatti S; Laboratory of Modeling and Computational Chemistry, Department of Biological Sciences and Health, Federal University of Amapá, Macapá, Brazil.
  • Alves LB; Bioinformatics Group, Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
  • Silva RC; Bioinformatics Group, Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
  • Ferreira EFB; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
  • Kimani NM; Graduate Program in Pharmaceutical Innovation, Department of Biological Sciences and Health, Federal University of Amapá, Macapá, Brazil.
  • Silva CHTP; Laboratory of Modeling and Computational Chemistry, Department of Biological Sciences and Health, Federal University of Amapá, Macapá, Brazil.
  • Souza JSN; Laboratory of Organic Chemistry and Biochemistry, University of the State of Amapá, Macapá, Brazil.
  • Espejo-Román JM; Department of Physical Sciences, University of Embu, Embu, Kenya.
  • Santos CBR; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
J Biomol Struct Dyn ; 40(12): 5386-5408, 2022 08.
Article en En | MEDLINE | ID: mdl-33427075
Cyclooxygenase 2 (COX-2) is a well-established target for the design of anti-inflammatory intermediates. Celecoxib was selected as a template molecule to perform ligand-based virtual screening, i.e. to search for structures with similarity in shape and electrostatic potential, with a gradual increase in accuracy through the combined fitting of several steps using eight commercial databases. The molecules ZINC408709 and ZINC2090319 reproduced values within the limits established in an initial study of absorption and distribution in the body. No alert was fired for possible toxic groups when these molecules were subjected to toxicity prediction. Molecular docking results with these compounds showed a higher binding affinity in comparison to rofecoxib for the COX-2 target. Additionally, ZINC408709 and ZINC2090319 were predicted to be potentially biologically active. In in silico prediction of endocrine disruption potential, it was established that the molecule ZINC2090319 binds strongly to the target related to cardiovascular risk in a desirable way as a non-steroidal antagonist and ZINC408709 binds strongly to the target that is associated with the treatment of inflammatory pathologies and similar to celecoxib. Metabolites generated from these compounds are less likely to have side effects. Simulations were used to evaluate the interaction of compounds with COX-1 and COX-2 during 200 ns. Despite the differences, ZINC408709 molecule showed better stability for COX-2 during molecular dynamics simulation. In the calculations of free energy MM/PBSA, the molecule ZINC408709 ΔGbind value has a higher affinity to celecoxib and rofecoxib COX-2. This demonstrates that the selected substances can be considered as promising COX-2 inhibitors. Communicated by Ramaswamy H. Sarma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de la Ciclooxigenasa 2 / Simulación de Dinámica Molecular Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Biomol Struct Dyn Año: 2022 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: Inhibidores de la Ciclooxigenasa 2 / Simulación de Dinámica Molecular Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Idioma: En Revista: J Biomol Struct Dyn Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido