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Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches

التفاصيل البيبلوغرافية
العنوان: Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches
المؤلفون: Sebastião Gomes Silva, Joaquín M. Campos, Pedro H F Araújo, Cleydson B. R. Santos, José M Espejo-Román, Ryan da Silva Ramos, Williams Jorge da Cruz Macêdo, Lúcio R de Lima, Jorddy Neves Cruz, Elenilze F B Ferreira
المساهمون: [Araújo,PHF, Ferreira,EFB, Macedo,WJC, Santos,CBR] Graduate Program in Innovation Pharmaceutical, Federal University of Amapá, Amapá-AP, Brazil. [Araújo,PHF, Ramos,RS, da Cruz,JN, de Lima,LR, Santos,CBR] Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá-AP, Brazil. [Silva,SG] Campus Abaetetuba, Universidade Federal do Para, Abaetetuba, Pará, Brazil. [Ferreira,EFB] Laboratory of Organic Chemistry and Biochemistry, University of State of Amapá, Macapá-AP, Brazil. [Macedo,WJC, Santos,CBR] Laboratory of Molecular Modeling and Simulation System, Federal Rural University of Amazônia, Capanema, Pará-PA, Brazil. [Espejo-Román,JM, Campos,JM] Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Biosanitary Institute of Granada (Ibs.GRANADA), University of Granada, Granada, Spain.
المصدر: Molecules, Vol 25, Iss 4183, p 4183 (2020)
Molecules
Digibug. Repositorio Institucional de la Universidad de Granada
instname
Digibug: Repositorio Institucional de la Universidad de Granada
Universidad de Granada (UGR)
Volume 25
Issue 18
بيانات النشر: MDPI AG, 2020.
سنة النشر: 2020
مصطلحات موضوعية: Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Protein Binding [Medical Subject Headings], Molecular model, Drug Evaluation, Preclinical, Pharmaceutical Science, Quantitative Structure-Activity Relationship, Inhibidores de la ciclooxigenasa 2, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Structure-Activity Relationship::Quantitative Structure-Activity Relationship [Medical Subject Headings], 01 natural sciences, In vivo tests, Analytical Chemistry, Madin Darby Canine Kidney Cells, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Lactones, Information Science::Information Science::Computing Methodologies::Software [Medical Subject Headings], Drug Discovery, Organisms::Eukaryota::Animals [Medical Subject Headings], Sulfones, 0303 health sciences, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Carnivora::Canidae::Dogs [Medical Subject Headings], Molecular Structure, Chemistry, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Evaluation, Preclinical [Medical Subject Headings], Molecular Docking Simulation, Anatomy::Cells::Epithelial Cells::Caco-2 Cells [Medical Subject Headings], in silico, Chemistry (miscellaneous), Lipinski's rule of five, Molecular Medicine, Regression Analysis, Pharmacophore, Protein Binding, Quantitative structure–activity relationship, In silico, 030303 biophysics, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Inhibitory Concentration 50 [Medical Subject Headings], Computational biology, Diseño de fármacos, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents::Anti-Inflammatory Agents, Non-Steroidal::Cyclooxygenase Inhibitors::Cyclooxygenase 2 Inhibitors [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking Simulation [Medical Subject Headings], Article, Permeability, COX-2 inhibitors, lcsh:QD241-441, 03 medical and health sciences, Inhibitory Concentration 50, Phenomena and Processes::Chemical Phenomena::Molecular Structure [Medical Subject Headings], Dogs, lcsh:Organic chemistry, Animals, Humans, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Design [Medical Subject Headings], Physical and Theoretical Chemistry, Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Sulfones [Medical Subject Headings], Inflammation, Virtual screening, Simulación por computador, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Regression Analysis [Medical Subject Headings], Binding Sites, Cyclooxygenase 2 Inhibitors, molecular modeling, Organic Chemistry, Information Science::Information Science::Computing Methodologies::Computer Simulation [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites [Medical Subject Headings], Zinc database, Phenomena and Processes::Chemical Phenomena::Permeability [Medical Subject Headings], 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Chemicals and Drugs::Organic Chemicals::Lactones [Medical Subject Headings], Celecoxib, Anatomy::Cells::Cells, Cultured::Cell Line::Madin Darby Canine Kidney Cells [Medical Subject Headings], Caco-2 Cells, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Software
الوصف: Non-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&rsquo
s correlation for the construction of quantitative structure&ndash
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 (&minus
log IC50) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski&rsquo
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.
وصف الملف: application/pdf
اللغة: English
تدمد: 1420-3049
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::871097a6b68ea05d9c0113ec3c201c39Test
https://www.mdpi.com/1420-3049/25/18/4183Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....871097a6b68ea05d9c0113ec3c201c39
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14203049