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Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent

Background and objectives: The clinical use of non-steroidal anti-inflammatory drugs is limited due to high incidence of adverse drug reactions. The pyrrole heterocycle is included in the chemical structure of a number of drugs with various activities and shows relatively good tolerability and safet...

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Autores principales: Zlatanova, Hristina, Vladimirova, Stanislava, Kostadinov, Ilia, Delev, Delian, Deneva, Tanya, Kostadinova, Ivanka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524057/
https://www.ncbi.nlm.nih.gov/pubmed/30959829
http://dx.doi.org/10.3390/medicina55040093
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author Zlatanova, Hristina
Vladimirova, Stanislava
Kostadinov, Ilia
Delev, Delian
Deneva, Tanya
Kostadinova, Ivanka
author_facet Zlatanova, Hristina
Vladimirova, Stanislava
Kostadinov, Ilia
Delev, Delian
Deneva, Tanya
Kostadinova, Ivanka
author_sort Zlatanova, Hristina
collection PubMed
description Background and objectives: The clinical use of non-steroidal anti-inflammatory drugs is limited due to high incidence of adverse drug reactions. The pyrrole heterocycle is included in the chemical structure of a number of drugs with various activities and shows relatively good tolerability and safety. The objectives of our study were to evaluate the analgesic and anti-inflammatory activity, as well as possible organ toxicity, of 2-[3-acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid (compound 3g), a novel N-pyrrolylcarboxylic acid structurally similar to celecoxib. Materials and methods: All experiments were performed on 6-week-old male Wistar rats divided into parallel groups (n = 8). Antinociception was assessed using animal pain models with thermal and chemical stimuli (paw withdrawal, tail-flick, and formalin tests). Criteria for the analgesic effect were increased latency in the paw withdrawal and tail-flick tests and decreased paw licking time in the formalin test compared to animals treated with saline (control). Anti-inflammatory activity was measured using a carrageenan-induced paw edema model; the criterion for anti-inflammatory effect was decreased edema compared to control. Blood samples were obtained after animals were sacrificed to assess possible organ toxicity. Statistical analysis was performed with IBM SPSS 20.0. Results: 2-[3-Acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid had analgesic action against chemical stimulus after single and multiple administration and against thermal stimulus after single administration. Compound 3g significantly suppressed carrageenan-induced paw edema after both single and continuous administration. After continuous administration, hematological tests showed that compound 3g decreased leukocyte and platelet levels and elevated serum creatinine levels. Conclusions: Antinociception with the tested compound is most likely mediated by spinal, peripheral, and anti-inflammatory mechanisms. Possible tolerance of the analgesic action at the spinal level develops after continuous administration. Anti-inflammatory activity is significant and probably the leading cause of antinociception. After multiple administration, compound 3g showed signs of potential nephrotoxicity and antiplatelet activity, as well as suppression of leukocyte levels.
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spelling pubmed-65240572019-06-04 Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent Zlatanova, Hristina Vladimirova, Stanislava Kostadinov, Ilia Delev, Delian Deneva, Tanya Kostadinova, Ivanka Medicina (Kaunas) Article Background and objectives: The clinical use of non-steroidal anti-inflammatory drugs is limited due to high incidence of adverse drug reactions. The pyrrole heterocycle is included in the chemical structure of a number of drugs with various activities and shows relatively good tolerability and safety. The objectives of our study were to evaluate the analgesic and anti-inflammatory activity, as well as possible organ toxicity, of 2-[3-acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid (compound 3g), a novel N-pyrrolylcarboxylic acid structurally similar to celecoxib. Materials and methods: All experiments were performed on 6-week-old male Wistar rats divided into parallel groups (n = 8). Antinociception was assessed using animal pain models with thermal and chemical stimuli (paw withdrawal, tail-flick, and formalin tests). Criteria for the analgesic effect were increased latency in the paw withdrawal and tail-flick tests and decreased paw licking time in the formalin test compared to animals treated with saline (control). Anti-inflammatory activity was measured using a carrageenan-induced paw edema model; the criterion for anti-inflammatory effect was decreased edema compared to control. Blood samples were obtained after animals were sacrificed to assess possible organ toxicity. Statistical analysis was performed with IBM SPSS 20.0. Results: 2-[3-Acetyl-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-3-(1H-indol-3-yl)-propionic acid had analgesic action against chemical stimulus after single and multiple administration and against thermal stimulus after single administration. Compound 3g significantly suppressed carrageenan-induced paw edema after both single and continuous administration. After continuous administration, hematological tests showed that compound 3g decreased leukocyte and platelet levels and elevated serum creatinine levels. Conclusions: Antinociception with the tested compound is most likely mediated by spinal, peripheral, and anti-inflammatory mechanisms. Possible tolerance of the analgesic action at the spinal level develops after continuous administration. Anti-inflammatory activity is significant and probably the leading cause of antinociception. After multiple administration, compound 3g showed signs of potential nephrotoxicity and antiplatelet activity, as well as suppression of leukocyte levels. MDPI 2019-04-05 /pmc/articles/PMC6524057/ /pubmed/30959829 http://dx.doi.org/10.3390/medicina55040093 Text en © 2019 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
Zlatanova, Hristina
Vladimirova, Stanislava
Kostadinov, Ilia
Delev, Delian
Deneva, Tanya
Kostadinova, Ivanka
Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent
title Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent
title_full Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent
title_fullStr Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent
title_full_unstemmed Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent
title_short Biological Screening of Novel Structural Analog of Celecoxib as Potential Anti-Inflammatory and Analgesic Agent
title_sort biological screening of novel structural analog of celecoxib as potential anti-inflammatory and analgesic agent
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524057/
https://www.ncbi.nlm.nih.gov/pubmed/30959829
http://dx.doi.org/10.3390/medicina55040093
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