Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors

A series of forty-five 1,5-diphenylpenta-2,4-dien-1-one analogues were synthesized and evaluated for their nitric oxide (NO) inhibition activity in IFN-γ/LPS-activated RAW 264.7 cells. Compounds 3h, 7a, 7d and 7e exhibited comparable or significantly higher activity than the standard, curcumin (IC50...

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Main Authors: Mohd Faudzi, S. M., Leong, S. W., Abas, F., Mohd Aluwi, M. F. F., Rullah, K., Lam, K. W., Ahmad, S., Tham, C. L., Shaari, K., Lajis, N. H.
Format: Article
Language:English
Published: Royal Society of Chemistry 2015
Online Access:http://psasir.upm.edu.my/id/eprint/46477/
http://psasir.upm.edu.my/id/eprint/46477/1/Synthesis%2C%20biological%20evaluation%20and%20QSAR%20studies%20of%20diarylpentanoid%20analogues%20as%20potential%20nitric%20oxide%20inhibitors.pdf
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author Mohd Faudzi, S. M.
Leong, S. W.
Abas, F.
Mohd Aluwi, M. F. F.
Rullah, K.
Lam, K. W.
Ahmad, S.
Tham, C. L.
Shaari, K.
Lajis, N. H.
author_facet Mohd Faudzi, S. M.
Leong, S. W.
Abas, F.
Mohd Aluwi, M. F. F.
Rullah, K.
Lam, K. W.
Ahmad, S.
Tham, C. L.
Shaari, K.
Lajis, N. H.
author_sort Mohd Faudzi, S. M.
building UPM Institutional Repository
collection Online Access
description A series of forty-five 1,5-diphenylpenta-2,4-dien-1-one analogues were synthesized and evaluated for their nitric oxide (NO) inhibition activity in IFN-γ/LPS-activated RAW 264.7 cells. Compounds 3h, 7a, 7d and 7e exhibited comparable or significantly higher activity than the standard, curcumin (IC50 = 14.69 ± 0.24 μM). Compound 7d, a 5-methylthiophenyl-bearing analogue, displayed the most promising NO-inhibitory activity with an IC50 value of 10.24 ± 0.62 μM. The 2D and 3D QSAR analyses performed revealed that a para-hydroxyl group on ring B and an α,β-unsaturated ketone moiety on the linker are crucial for a remarkable anti-inflammatory activity. Based on ADMET and TOPKAT analyses, compounds 3h, 7a and 7d are predicted to be nonmutagenic and to exhibit high blood–brain barrier (BBB) penetration, which indicates that they are potentially effective drug candidates for treating central nervous system (CNS) related disorders.
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spelling upm-464772018-02-27T03:20:48Z http://psasir.upm.edu.my/id/eprint/46477/ Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors Mohd Faudzi, S. M. Leong, S. W. Abas, F. Mohd Aluwi, M. F. F. Rullah, K. Lam, K. W. Ahmad, S. Tham, C. L. Shaari, K. Lajis, N. H. A series of forty-five 1,5-diphenylpenta-2,4-dien-1-one analogues were synthesized and evaluated for their nitric oxide (NO) inhibition activity in IFN-γ/LPS-activated RAW 264.7 cells. Compounds 3h, 7a, 7d and 7e exhibited comparable or significantly higher activity than the standard, curcumin (IC50 = 14.69 ± 0.24 μM). Compound 7d, a 5-methylthiophenyl-bearing analogue, displayed the most promising NO-inhibitory activity with an IC50 value of 10.24 ± 0.62 μM. The 2D and 3D QSAR analyses performed revealed that a para-hydroxyl group on ring B and an α,β-unsaturated ketone moiety on the linker are crucial for a remarkable anti-inflammatory activity. Based on ADMET and TOPKAT analyses, compounds 3h, 7a and 7d are predicted to be nonmutagenic and to exhibit high blood–brain barrier (BBB) penetration, which indicates that they are potentially effective drug candidates for treating central nervous system (CNS) related disorders. Royal Society of Chemistry 2015 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/46477/1/Synthesis%2C%20biological%20evaluation%20and%20QSAR%20studies%20of%20diarylpentanoid%20analogues%20as%20potential%20nitric%20oxide%20inhibitors.pdf Mohd Faudzi, S. M. and Leong, S. W. and Abas, F. and Mohd Aluwi, M. F. F. and Rullah, K. and Lam, K. W. and Ahmad, S. and Tham, C. L. and Shaari, K. and Lajis, N. H. (2015) Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors. MedChemComm, 6 (6). pp. 1069-1080. ISSN 2040-2503; ESSN: 2040-2511 http://pubs.rsc.org/en/journals/journalissues/md#!recentarticles&all 10.1039/c4md00541d
spellingShingle Mohd Faudzi, S. M.
Leong, S. W.
Abas, F.
Mohd Aluwi, M. F. F.
Rullah, K.
Lam, K. W.
Ahmad, S.
Tham, C. L.
Shaari, K.
Lajis, N. H.
Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors
title Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors
title_full Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors
title_fullStr Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors
title_full_unstemmed Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors
title_short Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors
title_sort synthesis, biological evaluation and qsar studies of diarylpentanoid analogues as potential nitric oxide inhibitors
url http://psasir.upm.edu.my/id/eprint/46477/
http://psasir.upm.edu.my/id/eprint/46477/
http://psasir.upm.edu.my/id/eprint/46477/
http://psasir.upm.edu.my/id/eprint/46477/1/Synthesis%2C%20biological%20evaluation%20and%20QSAR%20studies%20of%20diarylpentanoid%20analogues%20as%20potential%20nitric%20oxide%20inhibitors.pdf