Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies

In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 – 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 26...

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Main Authors:	Mohd Faudzi, Siti Munirah, Abdullah, Maryam Aisyah, Abdull Manap, Mohd Rashidi, Ismail, Ahmad Zaidi, Rullah, Kamal, Mohd Aluwi, Mohd Fadhlizil Fasihi, Mazila Ramli, Aizi Nor, Abas, Faridah, Lajis, Nordin H.
Format:	Article
Language:	English English
Published:	Elsevier 2019
Subjects:	RS403 Materia Medica-Pharmaceutical Chemistry
Online Access:	http://irep.iium.edu.my/77065/ http://irep.iium.edu.my/77065/ http://irep.iium.edu.my/77065/ http://irep.iium.edu.my/77065/1/Kamal%20Rullah%2022.pdf http://irep.iium.edu.my/77065/7/Scopus%20-%20kamal.pdf

id	iium-77065
recordtype	eprints
spelling	iium-770652019-12-12T08:21:05Z http://irep.iium.edu.my/77065/ Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies Mohd Faudzi, Siti Munirah Abdullah, Maryam Aisyah Abdull Manap, Mohd Rashidi Ismail, Ahmad Zaidi Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mazila Ramli, Aizi Nor Abas, Faridah Lajis, Nordin H. RS403 Materia Medica-Pharmaceutical Chemistry In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 – 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ± 1.5 μM and 12.1 ± 1.5 μM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action. Elsevier 2019-10-24 Article PeerReviewed application/pdf en http://irep.iium.edu.my/77065/1/Kamal%20Rullah%2022.pdf application/pdf en http://irep.iium.edu.my/77065/7/Scopus%20-%20kamal.pdf Mohd Faudzi, Siti Munirah and Abdullah, Maryam Aisyah and Abdull Manap, Mohd Rashidi and Ismail, Ahmad Zaidi and Rullah, Kamal and Mohd Aluwi, Mohd Fadhlizil Fasihi and Mazila Ramli, Aizi Nor and Abas, Faridah and Lajis, Nordin H. (2019) Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies. Bioorganic Chemistry. ISSN 0045-2068 (In Press) https://www.sciencedirect.com/science/article/pii/S0045206819315214 10.1016/j.bioorg.2019.103376
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	RS403 Materia Medica-Pharmaceutical Chemistry
spellingShingle	RS403 Materia Medica-Pharmaceutical Chemistry Mohd Faudzi, Siti Munirah Abdullah, Maryam Aisyah Abdull Manap, Mohd Rashidi Ismail, Ahmad Zaidi Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mazila Ramli, Aizi Nor Abas, Faridah Lajis, Nordin H. Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies
description	In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 – 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ± 1.5 μM and 12.1 ± 1.5 μM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action.
format	Article
author	Mohd Faudzi, Siti Munirah Abdullah, Maryam Aisyah Abdull Manap, Mohd Rashidi Ismail, Ahmad Zaidi Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mazila Ramli, Aizi Nor Abas, Faridah Lajis, Nordin H.
author_facet	Mohd Faudzi, Siti Munirah Abdullah, Maryam Aisyah Abdull Manap, Mohd Rashidi Ismail, Ahmad Zaidi Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mazila Ramli, Aizi Nor Abas, Faridah Lajis, Nordin H.
author_sort	Mohd Faudzi, Siti Munirah
title	Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies
title_short	Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies
title_full	Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies
title_fullStr	Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies
title_full_unstemmed	Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies
title_sort	inhibition of nitric oxide and prostaglandin e2 production by pyrrolylated-chalcones: synthesis, biological activity, crystal structure analysis, and molecular docking studies
publisher	Elsevier
publishDate	2019
url	http://irep.iium.edu.my/77065/ http://irep.iium.edu.my/77065/ http://irep.iium.edu.my/77065/ http://irep.iium.edu.my/77065/1/Kamal%20Rullah%2022.pdf http://irep.iium.edu.my/77065/7/Scopus%20-%20kamal.pdf
first_indexed	2023-09-18T21:48:46Z
last_indexed	2023-09-18T21:48:46Z
_version_	1777413628229582848

Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies

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