Araújo, Pedro H.F.Ramos, Ryan S.da Cruz, Jorddy N.Silva, Sebastiao G.Ferreira, Elenilze F.B.de Lima, Lúcio R.Macedo, Williams J.C.Espejo-Román, José M.Campos, Joaquín M.Santos, Cleydson B.R.2022-07-292022-07-292020-09-12Araújo PHF, Ramos RS, da Cruz JN, Silva SG, Ferreira EFB, de Lima LR, et al. Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches. Molecules. 2020 Sep 12;25(18):4183http://hdl.handle.net/10668/3846Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase-2 (COX-2) that were developed in order to avoid the side effects of non-selective inhibitors of COX-1. Thus, the present study aims to identify new selective chemical entities for the COX-2 enzyme via molecular modeling approaches. The best pharmacophore model was used to identify compounds within the ZINC database. The molecular properties were determined and selected with Pearson's correlation for the construction of quantitative structure-activity relationship (QSAR) models to predict the biological activities of the compounds obtained with virtual screening. The pharmacokinetic/toxicological profiles of the compounds were determined, as well as the binding modes through molecular docking compared to commercial compounds (rofecoxib and celecoxib). The QSAR analysis showed a fit with R = 0.9617, R2 = 0.9250, standard error of estimate (SEE) = 0.2238, and F = 46.2739, with the tetra-parametric regression model. After the analysis, only three promising inhibitors were selected, Z-964, Z-627, and Z-814, with their predicted pIC50 (-log IC50) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski's rule of five, which predicts a good oral availability and can be used in in vitro and in vivo tests in the zebrafish model in order to confirm the obtained in silico data.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/In silicoCOX-2 inhibitorsMolecular modelingSimulación por computadorInhibidores de la ciclooxigenasa 2Diseño de fármacosMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding SitesMedical Subject Headings::Anatomy::Cells::Epithelial Cells::Caco-2 CellsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents::Anti-Inflammatory Agents, Non-Steroidal::Cyclooxygenase Inhibitors::Cyclooxygenase 2 InhibitorsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Carnivora::Canidae::DogsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Evaluation, PreclinicalMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Inhibitory Concentration 50Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::LactonesMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Madin Darby Canine Kidney CellsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking SimulationMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Molecular StructureMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::PermeabilityMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Protein BindingMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Structure-Activity Relationship::Quantitative Structure-Activity RelationshipMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Regression AnalysisMedical Subject Headings::Information Science::Information Science::Computing Methodologies::SoftwareMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::SulfonesMedical Subject Headings::Information Science::Information Science::Computing Methodologies::Computer SimulationMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents::Anti-Inflammatory Agents, Non-Steroidal::Cyclooxygenase Inhibitors::Cyclooxygenase 2 InhibitorsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Designresearch article32932669Acceso abierto10.3390/molecules251841831420-3049PMC7570943