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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: Siti Munirah, Mohd Faudzi, Maryam Aisyah, Abdullah, Mohd Rashidi, Abdull Manap, Ahmad Zaidi, Ismail, Kamal, Rullah, Mohd F. F., Mohd Aluwi, Aizi Nor Mazila, Ramli, Faridah, Abas, Nordin, Lajis
Format: Article
Language:English
Published: Academic Press Inc. 2020
Subjects:
TP Chemical technology
Online Access:http://umpir.ump.edu.my/id/eprint/27773/1/Inhibition%20of%20nitric%20oxide%20and%20prostaglandin%20E2%20production%20.pdf
http://umpir.ump.edu.my/id/eprint/27773/
https://doi.org/10.1016/j.bioorg.2019.103376
https://doi.org/10.1016/j.bioorg.2019.103376
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spelling my.ump.umpir.277732020-12-23T04:30:47Z http://umpir.ump.edu.my/id/eprint/27773/ Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones : synthesis, biological activity, crystal structure analysis, and molecular docking studies Siti Munirah, Mohd Faudzi Maryam Aisyah, Abdullah Mohd Rashidi, Abdull Manap Ahmad Zaidi, Ismail Kamal, Rullah Mohd F. F., Mohd Aluwi Aizi Nor Mazila, Ramli Faridah, Abas Nordin, Lajis TP Chemical technology 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. Academic Press Inc. 2020-01 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/27773/1/Inhibition%20of%20nitric%20oxide%20and%20prostaglandin%20E2%20production%20.pdf Siti Munirah, Mohd Faudzi and Maryam Aisyah, Abdullah and Mohd Rashidi, Abdull Manap and Ahmad Zaidi, Ismail and Kamal, Rullah and Mohd F. F., Mohd Aluwi and Aizi Nor Mazila, Ramli and Faridah, Abas and Nordin, Lajis (2020) Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones : synthesis, biological activity, crystal structure analysis, and molecular docking studies. Bioorganic Chemistry, 94 (103376). pp. 1-12. ISSN 0045-2068 https://doi.org/10.1016/j.bioorg.2019.103376 https://doi.org/10.1016/j.bioorg.2019.103376
institution Universiti Malaysia Pahang
building UMP Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Pahang
content_source UMP Institutional Repository
url_provider http://umpir.ump.edu.my/
language English
topic TP Chemical technology
spellingShingle TP Chemical technology
Siti Munirah, Mohd Faudzi
Maryam Aisyah, Abdullah
Mohd Rashidi, Abdull Manap
Ahmad Zaidi, Ismail
Kamal, Rullah
Mohd F. F., Mohd Aluwi
Aizi Nor Mazila, Ramli
Faridah, Abas
Nordin, Lajis
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 Siti Munirah, Mohd Faudzi
Maryam Aisyah, Abdullah
Mohd Rashidi, Abdull Manap
Ahmad Zaidi, Ismail
Kamal, Rullah
Mohd F. F., Mohd Aluwi
Aizi Nor Mazila, Ramli
Faridah, Abas
Nordin, Lajis
author_facet Siti Munirah, Mohd Faudzi
Maryam Aisyah, Abdullah
Mohd Rashidi, Abdull Manap
Ahmad Zaidi, Ismail
Kamal, Rullah
Mohd F. F., Mohd Aluwi
Aizi Nor Mazila, Ramli
Faridah, Abas
Nordin, Lajis
author_sort Siti Munirah, Mohd Faudzi
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 Academic Press Inc.
publishDate 2020
url http://umpir.ump.edu.my/id/eprint/27773/1/Inhibition%20of%20nitric%20oxide%20and%20prostaglandin%20E2%20production%20.pdf
http://umpir.ump.edu.my/id/eprint/27773/
https://doi.org/10.1016/j.bioorg.2019.103376
https://doi.org/10.1016/j.bioorg.2019.103376
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score 13.211869

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