Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines

The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their e...

Full description

Bibliographic Details
Main Authors:	Mohd Aluwi, Mohd Fadhlizil Fasihi, Rullah, Kamal, Yamin, Bohari M., Leong, Sze Wei, Abdul Bahari, Mohd Nazri, Lim, Sock Jin, Mohd Faudzi, Siti Munirah, Jalil, Juriyati, Abas, Faridah, Mohd Fauzi, Norsyahida, Ismail, Nor Hadiani, Jantan, Ibrahim, Lam, Kok Wai
Format:	Article
Language:	English
Published:	Elsevier 2016
Subjects:	RS403 Materia Medica-Pharmaceutical Chemistry
Online Access:	http://irep.iium.edu.my/73763/ http://irep.iium.edu.my/73763/ http://irep.iium.edu.my/73763/ http://irep.iium.edu.my/73763/1/Kamal%20Rullah%2011.pdf

id	iium-73763
recordtype	eprints
spelling	iium-737632019-09-18T01:19:59Z http://irep.iium.edu.my/73763/ Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Yamin, Bohari M. Leong, Sze Wei Abdul Bahari, Mohd Nazri Lim, Sock Jin Mohd Faudzi, Siti Munirah Jalil, Juriyati Abas, Faridah Mohd Fauzi, Norsyahida Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai RS403 Materia Medica-Pharmaceutical Chemistry The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50 = 12.01 μM and 8c, IC50 = 4.86 μM) and U937 (8b, IC50 = 3.44 μM and 8c, IC50 = 1.65 μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50 = 0.78 μM and 15b, IC50 = 1.9 μM while U937: 15a, IC50 = 0.95 μM and 15b, IC50 = 0.92 μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD. Elsevier 2016-05 Article PeerReviewed application/pdf en http://irep.iium.edu.my/73763/1/Kamal%20Rullah%2011.pdf Mohd Aluwi, Mohd Fadhlizil Fasihi and Rullah, Kamal and Yamin, Bohari M. and Leong, Sze Wei and Abdul Bahari, Mohd Nazri and Lim, Sock Jin and Mohd Faudzi, Siti Munirah and Jalil, Juriyati and Abas, Faridah and Mohd Fauzi, Norsyahida and Ismail, Nor Hadiani and Jantan, Ibrahim and Lam, Kok Wai (2016) Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines. Bioorganic & Medicinal Chemistry Letters, 26 (10). pp. 2531-2538. ISSN 0960-894X https://www.sciencedirect.com/science/article/pii/S0960894X16303249 10.1016/j.bmcl.2016.03.092
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 Yamin, Bohari M. Leong, Sze Wei Abdul Bahari, Mohd Nazri Lim, Sock Jin Mohd Faudzi, Siti Munirah Jalil, Juriyati Abas, Faridah Mohd Fauzi, Norsyahida Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines
description	The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50 = 12.01 μM and 8c, IC50 = 4.86 μM) and U937 (8b, IC50 = 3.44 μM and 8c, IC50 = 1.65 μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50 = 0.78 μM and 15b, IC50 = 1.9 μM while U937: 15a, IC50 = 0.95 μM and 15b, IC50 = 0.92 μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD.
format	Article
author	Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Yamin, Bohari M. Leong, Sze Wei Abdul Bahari, Mohd Nazri Lim, Sock Jin Mohd Faudzi, Siti Munirah Jalil, Juriyati Abas, Faridah Mohd Fauzi, Norsyahida Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai
author_facet	Mohd Aluwi, Mohd Fadhlizil Fasihi Rullah, Kamal Yamin, Bohari M. Leong, Sze Wei Abdul Bahari, Mohd Nazri Lim, Sock Jin Mohd Faudzi, Siti Munirah Jalil, Juriyati Abas, Faridah Mohd Fauzi, Norsyahida Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai
author_sort	Mohd Aluwi, Mohd Fadhlizil Fasihi
title	Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines
title_short	Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines
title_full	Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines
title_fullStr	Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines
title_full_unstemmed	Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines
title_sort	synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin e2 production in lps-induced murine and human macrophages cell lines
publisher	Elsevier
publishDate	2016
url	http://irep.iium.edu.my/73763/ http://irep.iium.edu.my/73763/ http://irep.iium.edu.my/73763/ http://irep.iium.edu.my/73763/1/Kamal%20Rullah%2011.pdf
first_indexed	2023-09-18T21:44:35Z
last_indexed	2023-09-18T21:44:35Z
_version_	1777413364703559680

Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines

Similar Items