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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| Format: | Article |
| Language: | English English |
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SpringerLink
2017
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| Online Access: | http://irep.iium.edu.my/74211/ http://irep.iium.edu.my/74211/7/74211%20Suppression%20of%20PGE.pdf http://irep.iium.edu.my/74211/13/74211_Scopus_Suppression%20of%20PGE2%20production%20via%20disruption.pdf |
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| 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 |
| building | IIUM Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T17:32:43Z |
| format | Article |
| id | iium-74211 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-14T17:32:43Z |
| publishDate | 2017 |
| publisher | SpringerLink |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | iium-742112023-09-13T03:09:39Z 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 application/pdf en http://irep.iium.edu.my/74211/13/74211_Scopus_Suppression%20of%20PGE2%20production%20via%20disruption.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 |
| 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 |
| title | 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_short | 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 |
| topic | RS403 Materia Medica-Pharmaceutical Chemistry |
| 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 http://irep.iium.edu.my/74211/13/74211_Scopus_Suppression%20of%20PGE2%20production%20via%20disruption.pdf |