Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions
The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1584 |
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| author | Cleydson B. R. Santos Cleison C. Lobato Sirlene S. B. Ota Rai C. Silva Renata C. V. S. Bittencourt Jofre J. S. Freitas Elenilze F. B. Ferreira Marília B. Ferreira Renata C. Silva Anderson B. De Lima Joaquín M. Campos Rosivaldo S. Borges José A. H. M. Bittencourt |
| author_facet | Cleydson B. R. Santos Cleison C. Lobato Sirlene S. B. Ota Rai C. Silva Renata C. V. S. Bittencourt Jofre J. S. Freitas Elenilze F. B. Ferreira Marília B. Ferreira Renata C. Silva Anderson B. De Lima Joaquín M. Campos Rosivaldo S. Borges José A. H. M. Bittencourt |
| author_sort | Cleydson B. R. Santos |
| collection | DOAJ |
| description | The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using <sup>1</sup>H NMR and <sup>13</sup>C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (<i>Mus musculus</i> and <i>Homo sapiens</i>) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy. |
| first_indexed | 2024-03-09T16:32:08Z |
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| id | doaj.art-3c7c83face0f40d4a86f319b8878dae4 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:08Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-3c7c83face0f40d4a86f319b8878dae42023-11-24T15:00:23ZengMDPI AGPharmaceuticals1424-82472023-11-011611158410.3390/ph16111584Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target InteractionsCleydson B. R. Santos0Cleison C. Lobato1Sirlene S. B. Ota2Rai C. Silva3Renata C. V. S. Bittencourt4Jofre J. S. Freitas5Elenilze F. B. Ferreira6Marília B. Ferreira7Renata C. Silva8Anderson B. De Lima9Joaquín M. Campos10Rosivaldo S. Borges11José A. H. M. Bittencourt12Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, BrazilGraduate Program on Medicinal Chemistry and Molecular Modeling, Institute of Health Science, Federal University of Pará, Belém 66075-110, PA, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, BrazilLaboratory of Morphophysiology Applied to Health, State University of Pará, Belém 66095-662, PA, BrazilLaboratory of Organic Chemistry and Biochemistry, University of the State of Amapá, Macapá 68900-070, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, BrazilLaboratory of Morphophysiology Applied to Health, State University of Pará, Belém 66095-662, PA, BrazilLaboratory of Morphophysiology Applied to Health, State University of Pará, Belém 66095-662, PA, BrazilDepartment of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, University of Granada, 18071 Granada, SpainGraduate Program on Medicinal Chemistry and Molecular Modeling, Institute of Health Science, Federal University of Pará, Belém 66075-110, PA, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68902-280, AP, BrazilThe design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using <sup>1</sup>H NMR and <sup>13</sup>C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (<i>Mus musculus</i> and <i>Homo sapiens</i>) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.https://www.mdpi.com/1424-8247/16/11/1584analgesic5-acetamido-2-hydroxy benzoic acidmolecular dockingADMEtoxicity |
| spellingShingle | Cleydson B. R. Santos Cleison C. Lobato Sirlene S. B. Ota Rai C. Silva Renata C. V. S. Bittencourt Jofre J. S. Freitas Elenilze F. B. Ferreira Marília B. Ferreira Renata C. Silva Anderson B. De Lima Joaquín M. Campos Rosivaldo S. Borges José A. H. M. Bittencourt Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions Pharmaceuticals analgesic 5-acetamido-2-hydroxy benzoic acid molecular docking ADME toxicity |
| title | Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions |
| title_full | Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions |
| title_fullStr | Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions |
| title_full_unstemmed | Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions |
| title_short | Analgesic Activity of 5-Acetamido-2-Hydroxy Benzoic Acid Derivatives and an In-Vivo and In-Silico Analysis of Their Target Interactions |
| title_sort | analgesic activity of 5 acetamido 2 hydroxy benzoic acid derivatives and an in vivo and in silico analysis of their target interactions |
| topic | analgesic 5-acetamido-2-hydroxy benzoic acid molecular docking ADME toxicity |
| url | https://www.mdpi.com/1424-8247/16/11/1584 |
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