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Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential

OBJECTIVE(S): The novel 1,5-diaryl-1,4-pentadien-3-one derivatives were studied for analgesic, anti-inflammatory and anticancer potential to establish their role in pain, inflammatory disorders and cancer. MATERIALS AND METHODS: Two 1,5- diaryl-1,4-pentadien-3-one derivatives: (1E,4E)- 5-(4-fluoro p...

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Autores principales: Tariq, Muhammad Sheraz, Khan, Arif-ullah, Minhas, Amber Mahmood, Filho, Edson Rodrigues, Din, Zia ud, Khan, Aslam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437456/
https://www.ncbi.nlm.nih.gov/pubmed/30944711
http://dx.doi.org/10.22038/ijbms.2018.31261.7536
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author Tariq, Muhammad Sheraz
Khan, Arif-ullah
Minhas, Amber Mahmood
Filho, Edson Rodrigues
Din, Zia ud
Khan, Aslam
author_facet Tariq, Muhammad Sheraz
Khan, Arif-ullah
Minhas, Amber Mahmood
Filho, Edson Rodrigues
Din, Zia ud
Khan, Aslam
author_sort Tariq, Muhammad Sheraz
collection PubMed
description OBJECTIVE(S): The novel 1,5-diaryl-1,4-pentadien-3-one derivatives were studied for analgesic, anti-inflammatory and anticancer potential to establish their role in pain, inflammatory disorders and cancer. MATERIALS AND METHODS: Two 1,5- diaryl-1,4-pentadien-3-one derivatives: (1E,4E)- 5-(4-fluoro phenyl)-1-(4-methoxyphenyl)- 2-methylpenta-1,4-dien-3-one (A2K2A17) and (1E,4E)-5-(4-nitrophenyl)-1-(4-nitrophenyl)-2-ethylhexa-1,4-dien-3-one (A11K3A11) were synthesized and characterized via 1H NMR and 13C NMR techniques. Molecular docking, anti-inflammatory, analgesic and anticancer activities were performed using Auto Doc Vina, carrageenan mediated paw edema and formalin induced chronic inflammation, acetic acid induced writhings and hotplate assay and brine-shrimp lethality assay. RESULTS: A2K2A17 and A11K3A11 showed high computational affinities (binding energy > -9.0 Kcal/mol) against COX-1, kappa receptor and braf kinase domain. A2K2A17 and A11K3A11 exhibited moderate docking affinities (binding energy > -8.0 Kcal/mol) against COX-2, human capsaicin receptor, tumor necrosis factor, lipoxygenase, colony stimulating factor, delta receptor, cyclin dependent protein kinase-2, mitogen activated kinase, mu receptor and kit kinase domain. A2K2A17 and A11K3A11 possess low docking affinities (binding energy > -7.0 Kcal/mol) against purinoceptor, platelets-derived growth Factor-1 and vascular-endothelial growth factor. In analgesic activity, A2K2A17 (1-30 mg/kg) and A11K3A11 (1-10 mg/kg) decreased acetic acid induced writhes and prolonged the latency time (P<0.01, P<0.001 vs saline group) respectively. A2K2A17 (10-30 mg/kg) and A11K3A11 (1-10 mg/kg) reduced carrageenan as well as formalin mediated edema (P<0.01, P<0.001). A2K2A17 found effective for cytotoxicity assay with LC(50) value 1.5 µg/ml. CONCLUSION: The in silico, in vitro and in vivo studies on A2K2A17 and A11K3A11 reports their computational binding affinities against targets as well as the analgesic, anti-inflammatory and the anticancer effects.
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spelling pubmed-64374562019-04-03 Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential Tariq, Muhammad Sheraz Khan, Arif-ullah Minhas, Amber Mahmood Filho, Edson Rodrigues Din, Zia ud Khan, Aslam Iran J Basic Med Sci Original Article OBJECTIVE(S): The novel 1,5-diaryl-1,4-pentadien-3-one derivatives were studied for analgesic, anti-inflammatory and anticancer potential to establish their role in pain, inflammatory disorders and cancer. MATERIALS AND METHODS: Two 1,5- diaryl-1,4-pentadien-3-one derivatives: (1E,4E)- 5-(4-fluoro phenyl)-1-(4-methoxyphenyl)- 2-methylpenta-1,4-dien-3-one (A2K2A17) and (1E,4E)-5-(4-nitrophenyl)-1-(4-nitrophenyl)-2-ethylhexa-1,4-dien-3-one (A11K3A11) were synthesized and characterized via 1H NMR and 13C NMR techniques. Molecular docking, anti-inflammatory, analgesic and anticancer activities were performed using Auto Doc Vina, carrageenan mediated paw edema and formalin induced chronic inflammation, acetic acid induced writhings and hotplate assay and brine-shrimp lethality assay. RESULTS: A2K2A17 and A11K3A11 showed high computational affinities (binding energy > -9.0 Kcal/mol) against COX-1, kappa receptor and braf kinase domain. A2K2A17 and A11K3A11 exhibited moderate docking affinities (binding energy > -8.0 Kcal/mol) against COX-2, human capsaicin receptor, tumor necrosis factor, lipoxygenase, colony stimulating factor, delta receptor, cyclin dependent protein kinase-2, mitogen activated kinase, mu receptor and kit kinase domain. A2K2A17 and A11K3A11 possess low docking affinities (binding energy > -7.0 Kcal/mol) against purinoceptor, platelets-derived growth Factor-1 and vascular-endothelial growth factor. In analgesic activity, A2K2A17 (1-30 mg/kg) and A11K3A11 (1-10 mg/kg) decreased acetic acid induced writhes and prolonged the latency time (P<0.01, P<0.001 vs saline group) respectively. A2K2A17 (10-30 mg/kg) and A11K3A11 (1-10 mg/kg) reduced carrageenan as well as formalin mediated edema (P<0.01, P<0.001). A2K2A17 found effective for cytotoxicity assay with LC(50) value 1.5 µg/ml. CONCLUSION: The in silico, in vitro and in vivo studies on A2K2A17 and A11K3A11 reports their computational binding affinities against targets as well as the analgesic, anti-inflammatory and the anticancer effects. Mashhad University of Medical Sciences 2019-01 /pmc/articles/PMC6437456/ /pubmed/30944711 http://dx.doi.org/10.22038/ijbms.2018.31261.7536 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Tariq, Muhammad Sheraz
Khan, Arif-ullah
Minhas, Amber Mahmood
Filho, Edson Rodrigues
Din, Zia ud
Khan, Aslam
Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
title Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
title_full Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
title_fullStr Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
title_full_unstemmed Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
title_short Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
title_sort computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437456/
https://www.ncbi.nlm.nih.gov/pubmed/30944711
http://dx.doi.org/10.22038/ijbms.2018.31261.7536
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