Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives

Curcumin is an important molecule found in turmeric plants and has been reported to exhibit some profound anti-inflammatory activities by interacting with several important molecular targets found in the mitogenactivated protein kinase and NF-κβ pathways. As part of our continuing effort to search f...

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Main Authors:	Mohd Aluwi, Mohd Fadhlizil Fasihi, Rullah, Kamal, Haque, Md. Areeful, Yamin, Bohari M., Ahmad, Waqas, Amjad, Muhammad Wahab, Leong, Sze Wei, Fahmizar, Nurul Amira, Jalil, Juriyati, Abas, Faridah, Ismail, Nor Hadiani, Jantan, Ibrahim, Lam, Kok Wai
Format:	Article
Language:	English
Published:	SpringerLink 2017
Subjects:	RS403 Materia Medica-Pharmaceutical Chemistry
Online Access:	http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/7/74211%20Suppression%20of%20PGE.pdf

id	iium-74211
recordtype	eprints
spelling	iium-742112019-09-19T01:19:58Z http://irep.iium.edu.my/74211/ Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Haque, Md. Areeful Yamin, Bohari M. Ahmad, Waqas Amjad, Muhammad Wahab Leong, Sze Wei Fahmizar, Nurul Amira Jalil, Juriyati Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai RS403 Materia Medica-Pharmaceutical Chemistry Curcumin is an important molecule found in turmeric plants and has been reported to exhibit some profound anti-inflammatory activities by interacting with several important molecular targets found in the mitogenactivated protein kinase and NF-κβ pathways. As part of our continuing effort to search for new anti-inflammatory agents with better in vitro and in vivo efficacies, we have synthesized a series of new unsymmetrical dicarbonyl curcumin derivatives and tested their effects on prostaglandin E2 secretion level in interferon-γ/lipopolysaccharide-activated macrophage cells. Among those, five compounds exhibited remarkable suppression on prostaglandin E2 production with IC50 values ranging from 0.87 to 18.41 μM. The most potent compound 17f was found to down-regulate the expression of cyclooxygenase-2 mRNA suggesting that this series of compounds could possibly target the mitogenactivated protein kinase signal transduction pathway. Whilst the compound did not affect the expression of the conventional mitogen-activated protein kinases, the results suggest that it could disrupt the phosphorylation and activation of the proteins particularly the c-Jun N-terminal kinases. Finally, the binding interactions were examined using the molecular docking and dynamics simulation approaches. SpringerLink 2017-12 Article PeerReviewed application/pdf en http://irep.iium.edu.my/74211/7/74211%20Suppression%20of%20PGE.pdf Mohd Aluwi, Mohd Fadhlizil Fasihi and Rullah, Kamal and Haque, Md. Areeful and Yamin, Bohari M. and Ahmad, Waqas and Amjad, Muhammad Wahab and Leong, Sze Wei and Fahmizar, Nurul Amira and Jalil, Juriyati and Abas, Faridah and Ismail, Nor Hadiani and Jantan, Ibrahim and Lam, Kok Wai (2017) Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives. Medicinal Chemistry Research, 26 (12). pp. 3323-3335. ISSN 1054-2523 E-ISSN 1554-8120 https://link.springer.com/article/10.1007/s00044-017-2025-4 10.1007/s00044-017-2025-4
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RS403 Materia Medica-Pharmaceutical Chemistry
spellingShingle	RS403 Materia Medica-Pharmaceutical Chemistry Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Haque, Md. Areeful Yamin, Bohari M. Ahmad, Waqas Amjad, Muhammad Wahab Leong, Sze Wei Fahmizar, Nurul Amira Jalil, Juriyati Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
description	Curcumin is an important molecule found in turmeric plants and has been reported to exhibit some profound anti-inflammatory activities by interacting with several important molecular targets found in the mitogenactivated protein kinase and NF-κβ pathways. As part of our continuing effort to search for new anti-inflammatory agents with better in vitro and in vivo efficacies, we have synthesized a series of new unsymmetrical dicarbonyl curcumin derivatives and tested their effects on prostaglandin E2 secretion level in interferon-γ/lipopolysaccharide-activated macrophage cells. Among those, five compounds exhibited remarkable suppression on prostaglandin E2 production with IC50 values ranging from 0.87 to 18.41 μM. The most potent compound 17f was found to down-regulate the expression of cyclooxygenase-2 mRNA suggesting that this series of compounds could possibly target the mitogenactivated protein kinase signal transduction pathway. Whilst the compound did not affect the expression of the conventional mitogen-activated protein kinases, the results suggest that it could disrupt the phosphorylation and activation of the proteins particularly the c-Jun N-terminal kinases. Finally, the binding interactions were examined using the molecular docking and dynamics simulation approaches.
format	Article
author	Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Haque, Md. Areeful Yamin, Bohari M. Ahmad, Waqas Amjad, Muhammad Wahab Leong, Sze Wei Fahmizar, Nurul Amira Jalil, Juriyati Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai
author_facet	Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Haque, Md. Areeful Yamin, Bohari M. Ahmad, Waqas Amjad, Muhammad Wahab Leong, Sze Wei Fahmizar, Nurul Amira Jalil, Juriyati Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai
author_sort	Mohd Aluwi, Mohd Fadhlizil Fasihi
title	Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
title_short	Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
title_full	Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
title_fullStr	Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
title_full_unstemmed	Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
title_sort	suppression of pge2 production via disruption of mapk phosphorylation by unsymmetrical dicarbonyl curcumin derivatives
publisher	SpringerLink
publishDate	2017
url	http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/7/74211%20Suppression%20of%20PGE.pdf
first_indexed	2023-09-18T21:45:08Z
last_indexed	2023-09-18T21:45:08Z
_version_	1777413398980460544

Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives

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