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New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-...

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Autores principales: Tratrat, Christophe, Haroun, Michelyne, Paparisva, Aliki, Kamoutsis, Charalmpos, Petrou, Anthi, Gavalas, Antonis, Eleftheriou, Phaedra, Geronikaki, Athina, Venugopala, Katharigatta N., Kochkar, Hafedh, Nair, Anroop B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866232/
https://www.ncbi.nlm.nih.gov/pubmed/33513963
http://dx.doi.org/10.3390/molecules26030659
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author Tratrat, Christophe
Haroun, Michelyne
Paparisva, Aliki
Kamoutsis, Charalmpos
Petrou, Anthi
Gavalas, Antonis
Eleftheriou, Phaedra
Geronikaki, Athina
Venugopala, Katharigatta N.
Kochkar, Hafedh
Nair, Anroop B.
author_facet Tratrat, Christophe
Haroun, Michelyne
Paparisva, Aliki
Kamoutsis, Charalmpos
Petrou, Anthi
Gavalas, Antonis
Eleftheriou, Phaedra
Geronikaki, Athina
Venugopala, Katharigatta N.
Kochkar, Hafedh
Nair, Anroop B.
author_sort Tratrat, Christophe
collection PubMed
description Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.
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spelling pubmed-78662322021-02-07 New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents Tratrat, Christophe Haroun, Michelyne Paparisva, Aliki Kamoutsis, Charalmpos Petrou, Anthi Gavalas, Antonis Eleftheriou, Phaedra Geronikaki, Athina Venugopala, Katharigatta N. Kochkar, Hafedh Nair, Anroop B. Molecules Article Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms. MDPI 2021-01-27 /pmc/articles/PMC7866232/ /pubmed/33513963 http://dx.doi.org/10.3390/molecules26030659 Text en © 2021 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tratrat, Christophe
Haroun, Michelyne
Paparisva, Aliki
Kamoutsis, Charalmpos
Petrou, Anthi
Gavalas, Antonis
Eleftheriou, Phaedra
Geronikaki, Athina
Venugopala, Katharigatta N.
Kochkar, Hafedh
Nair, Anroop B.
New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
title New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
title_full New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
title_fullStr New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
title_full_unstemmed New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
title_short New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
title_sort new substituted 5-benzylideno-2-adamantylthiazol[3,2-b][1,2,4]triazol-6(5h)ones as possible anti-inflammatory agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866232/
https://www.ncbi.nlm.nih.gov/pubmed/33513963
http://dx.doi.org/10.3390/molecules26030659
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