Cargando…

Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids

Six β-hydroxy-β-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expec...

Descripción completa

Detalles Bibliográficos
Autores principales: Savić, Jelena S., Dilber, Sanda P., Marković, Bojan D., Milenković, Marina T., Vladimirov, Sote M., Juranić, Ivan O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264771/
https://www.ncbi.nlm.nih.gov/pubmed/25134768
http://dx.doi.org/10.3390/molecules16086645
_version_ 1783375563903205376
author Savić, Jelena S.
Dilber, Sanda P.
Marković, Bojan D.
Milenković, Marina T.
Vladimirov, Sote M.
Juranić, Ivan O.
author_facet Savić, Jelena S.
Dilber, Sanda P.
Marković, Bojan D.
Milenković, Marina T.
Vladimirov, Sote M.
Juranić, Ivan O.
author_sort Savić, Jelena S.
collection PubMed
description Six β-hydroxy-β-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the β-hydroxy-β-aryl propanoic acids, and to elucidate the effect α-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 µmol/kg and 15 µmol/kg, while the result for ibuprofen is 51.7 µmol/kg. Only slight hyperaemia or few petechiae were spotted on rat’s stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenyl-propanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions.
format Online
Article
Text
id pubmed-6264771
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62647712018-12-10 Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids Savić, Jelena S. Dilber, Sanda P. Marković, Bojan D. Milenković, Marina T. Vladimirov, Sote M. Juranić, Ivan O. Molecules Article Six β-hydroxy-β-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the β-hydroxy-β-aryl propanoic acids, and to elucidate the effect α-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 µmol/kg and 15 µmol/kg, while the result for ibuprofen is 51.7 µmol/kg. Only slight hyperaemia or few petechiae were spotted on rat’s stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenyl-propanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions. MDPI 2011-08-05 /pmc/articles/PMC6264771/ /pubmed/25134768 http://dx.doi.org/10.3390/molecules16086645 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Savić, Jelena S.
Dilber, Sanda P.
Marković, Bojan D.
Milenković, Marina T.
Vladimirov, Sote M.
Juranić, Ivan O.
Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
title Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
title_full Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
title_fullStr Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
title_full_unstemmed Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
title_short Docking Studies and α-Substitution Effects on the Anti-Inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids
title_sort docking studies and α-substitution effects on the anti-inflammatory activity of β-hydroxy-β-arylpropanoic acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264771/
https://www.ncbi.nlm.nih.gov/pubmed/25134768
http://dx.doi.org/10.3390/molecules16086645
work_keys_str_mv AT savicjelenas dockingstudiesandasubstitutioneffectsontheantiinflammatoryactivityofbhydroxybarylpropanoicacids
AT dilbersandap dockingstudiesandasubstitutioneffectsontheantiinflammatoryactivityofbhydroxybarylpropanoicacids
AT markovicbojand dockingstudiesandasubstitutioneffectsontheantiinflammatoryactivityofbhydroxybarylpropanoicacids
AT milenkovicmarinat dockingstudiesandasubstitutioneffectsontheantiinflammatoryactivityofbhydroxybarylpropanoicacids
AT vladimirovsotem dockingstudiesandasubstitutioneffectsontheantiinflammatoryactivityofbhydroxybarylpropanoicacids
AT juranicivano dockingstudiesandasubstitutioneffectsontheantiinflammatoryactivityofbhydroxybarylpropanoicacids