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

Mohd Faudzi, Siti Munirah Mohd Faudzi and Leong, Sze Wei and Abas, Faridah and Mohd Aluwi, Mohd Fadhlizil Fasihi and Rullah, Kamal and Lam, Kok Wai and Ahmad, Syahida and Ling Tham, Chau Ling Tham and Lajis, Nordin H. (2015) Synthesis, biological evaluation and QSAR studies of diarylpentanoid analogues as potential nitric oxideinhibitors. Medicinal Chemistry Communication, 6. pp. 1069-1080. ISSN 2040-2511

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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 (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.

Item Type: Article (Journal)
Additional Information: 9020/73544
Uncontrolled Keywords: Synthesis, biological evaluation and QSAR; Diarylpentanoid analogues; Nitric oxideinhibitors
Subjects: R Medicine > RS Pharmacy and materia medica > RS403 Materia Medica-Pharmaceutical Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry
Depositing User: Dr Kamal Rullah
Date Deposited: 13 Sep 2019 09:00
Last Modified: 13 Sep 2019 09:08
URI: http://irep.iium.edu.my/id/eprint/73544

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