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

S. M. Mohd Faudzi, S. W. Leong, F. Abas, M. F F Mohd Aluwi, K. Rullah, Kok Wai Lam, S. Ahmad, C. L. Tham, K. Shaari, N. H. Lajis

Research output: Contribution to journalArticle

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Abstract

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 (IC<inf>50</inf> = 14.69 ± 0.24 μM). Compound 7d, a 5-methylthiophenyl-bearing analogue, displayed the most promising NO-inhibitory activity with an IC<inf>50</inf> 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.

Original languageEnglish
Pages (from-to)1069-1080
Number of pages12
JournalMedChemComm
Volume6
Issue number6
DOIs
Publication statusPublished - 1 Jun 2015

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Quantitative Structure-Activity Relationship
Inhibitory Concentration 50
Nitric Oxide
Bearings (structural)
Curcumin
Central Nervous System Diseases
Neurology
Ketones
Blood-Brain Barrier
Hydroxyl Radical
Anti-Inflammatory Agents
Pharmaceutical Preparations
RAW 264.7 Cells

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Cite this

Mohd Faudzi, S. M., Leong, S. W., Abas, F., Mohd Aluwi, M. F. F., Rullah, K., Lam, K. W., ... Lajis, N. H. (2015). Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors. MedChemComm, 6(6), 1069-1080. https://doi.org/10.1039/c4md00541d

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, Kok Wai; Ahmad, S.; Tham, C. L.; Shaari, K.; Lajis, N. H.

In: MedChemComm, Vol. 6, No. 6, 01.06.2015, p. 1069-1080.

Research output: Contribution to journalArticle

Mohd Faudzi, SM, Leong, SW, Abas, F, Mohd Aluwi, MFF, Rullah, K, Lam, KW, Ahmad, S, Tham, CL, Shaari, K & Lajis, NH 2015, 'Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors', MedChemComm, vol. 6, no. 6, pp. 1069-1080. https://doi.org/10.1039/c4md00541d
Mohd Faudzi, S. M. ; Leong, S. W. ; Abas, F. ; Mohd Aluwi, M. F F ; Rullah, K. ; Lam, Kok Wai ; Ahmad, S. ; Tham, C. L. ; Shaari, K. ; Lajis, N. H. / Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxide inhibitors. In: MedChemComm. 2015 ; Vol. 6, No. 6. pp. 1069-1080.
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