دورية أكاديمية
Antiplatelet pyrazolopyridines derivatives: pharmacological, biochemical and toxicological characterization.
| العنوان: | Antiplatelet pyrazolopyridines derivatives: pharmacological, biochemical and toxicological characterization. |
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| المؤلفون: | Saito MS; a Laboratório de Antibióticos , Bioquímica, Ensino e Modelagem Molecular (LABiEMol) - Instituto de Biologia, Universidade Federal Fluminense , Niterói , Brazil .; b Programa de Pós-Graduação em Patologia (PPG-UFF) - Hospital Universitário Antônio Pedro, Universidade Federal Fluminense , Niterói , Brazil ., Lourenço AL; a Laboratório de Antibióticos , Bioquímica, Ensino e Modelagem Molecular (LABiEMol) - Instituto de Biologia, Universidade Federal Fluminense , Niterói , Brazil .; b Programa de Pós-Graduação em Patologia (PPG-UFF) - Hospital Universitário Antônio Pedro, Universidade Federal Fluminense , Niterói , Brazil ., Dias LR; c Laboratório de Química Medicinal (LQMed) - Faculdade de Farmácia , Universidade Federal Fluminense , Niterói , Brazil ., Freitas AC; c Laboratório de Química Medicinal (LQMed) - Faculdade de Farmácia , Universidade Federal Fluminense , Niterói , Brazil ., Vitorino MI; a Laboratório de Antibióticos , Bioquímica, Ensino e Modelagem Molecular (LABiEMol) - Instituto de Biologia, Universidade Federal Fluminense , Niterói , Brazil ., Albuquerque MG; d Laboratório de Modelagem Molecular (LabMMol) - Instituto de Química ., Rodrigues CR; e Laboratório de Modelagem Molecular e QSAR (ModMolQSAR) - Faculdade de Farmácia , and., Cabral LM; f Laboratório de Tecnologia Industrial Farmacêutica (LabTIF) - Faculdade de Farmácia , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil., Dias EP; b Programa de Pós-Graduação em Patologia (PPG-UFF) - Hospital Universitário Antônio Pedro, Universidade Federal Fluminense , Niterói , Brazil ., Castro HC; a Laboratório de Antibióticos , Bioquímica, Ensino e Modelagem Molecular (LABiEMol) - Instituto de Biologia, Universidade Federal Fluminense , Niterói , Brazil .; b Programa de Pós-Graduação em Patologia (PPG-UFF) - Hospital Universitário Antônio Pedro, Universidade Federal Fluminense , Niterói , Brazil ., Satlher PC; a Laboratório de Antibióticos , Bioquímica, Ensino e Modelagem Molecular (LABiEMol) - Instituto de Biologia, Universidade Federal Fluminense , Niterói , Brazil .; f Laboratório de Tecnologia Industrial Farmacêutica (LabTIF) - Faculdade de Farmácia , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil. |
| المصدر: | Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2016 Dec; Vol. 31 (6), pp. 1591-601. Date of Electronic Publication: 2016 Mar 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 101150203 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1475-6374 (Electronic) Linking ISSN: 14756366 NLM ISO Abbreviation: J Enzyme Inhib Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Basingstoke, UK : Taylor & Francis, c2002- |
| مواضيع طبية MeSH: | Platelet Aggregation Inhibitors/*pharmacology , Pyrazoles/*pharmacology , Pyridines/*pharmacology, Animals ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Platelet Aggregation Inhibitors/chemistry ; Platelet Aggregation Inhibitors/toxicity ; Pyrazoles/chemistry ; Pyrazoles/toxicity ; Pyridines/chemistry ; Pyridines/toxicity |
| مستخلص: | Platelet aggregation is one of the main events involved in vascular thrombus formation. Recently, N'-substituted-phenylmethylene-3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazides were described as antiplatelet derivatives. In this work, we explore the properties of these antiplatelet agents through a series of pharmacological, biochemical and toxicological studies. The antiplatelet activity of each derivative was confirmed as 3a, 3b and 3 h significantly inhibited human platelet aggregation induced by arachidonic acid, with no detectable effect on clotting factors or healthy erythrocytes. Importantly, mice treated with derivative 3a showed a higher survival rate at an in vivo model of pulmonary thromboembolism with a lower bleeding risk in comparison to aspirin. The in silico studies pointed a series of structural parameters related to thromboxane synthase (TXS) inhibition by 3a, which was confirmed by tracking plasma levels of PGE2 and TXB2 through an in vitro enzyme immunoassay. Derivative 3a showed selective TXS inhibition allied with low bleeding risk and increased animal survival, revealing the derivative as a promising candidate for treatment of cardiovascular diseases. |
| فهرسة مساهمة: | Keywords: Antihemostatic; antiplatelet; molecular modeling; pyrazolopyridine derivatives; thrombosis |
| المشرفين على المادة: | 0 (Platelet Aggregation Inhibitors) 0 (Pyrazoles) 0 (Pyridines) 0 (pyrazolopyridine) |
| تواريخ الأحداث: | Date Created: 20160323 Date Completed: 20170306 Latest Revision: 20170306 |
| رمز التحديث: | 20221213 |
| DOI: | 10.3109/14756366.2016.1158712 |
| PMID: | 27000933 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1475-6374 |
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| DOI: | 10.3109/14756366.2016.1158712 |