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

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

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Abstract

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.

Item Type: Article (Journal)
Additional Information: 9020/74211
Uncontrolled Keywords: Prostaglandin E2 ● COX-2 mRNA expression ● MAPK phosphorylation ● Molecular ● Dynamic simulation ● Unsymmetrical dicarbonyl curcumin derivatives
Subjects: R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry
Kulliyyah of Pharmacy
Depositing User: Dr Kamal Rullah
Date Deposited: 19 Sep 2019 09:19
Last Modified: 19 Sep 2019 09:19
URI: http://irep.iium.edu.my/id/eprint/74211

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