Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives

Sze Wei Leong; Siti Munirah Mohd Faudzi; Faridah Abas; Mohd Fadhlizil Fasihi Mohd Aluwi; Kamal Rullah; Kok Wai Lam; Mohd Nazri Abdul Bahari; Syahida Ahmad; Chau Ling Tham; Khozirah Shaari; Nordin H Lajis

doi:10.1016/j.bmcl.2015.05.056

Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3330-7. doi: 10.1016/j.bmcl.2015.05.056. Epub 2015 May 30.

Affiliations

¹ Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
² Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
³ Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Electronic address: faridah_abas@upm.edu.my.
⁴ Drug and Herbal Research Centre Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia.
⁵ Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
⁶ Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
⁷ Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. Electronic address: nordinlajis@gmail.com.

PMID: 26071636
DOI: 10.1016/j.bmcl.2015.05.056

Abstract

A series of twenty-four 2-benzoyl-6-benzylidenecyclohexanone analogs were synthesized and evaluated for their nitric oxide inhibition and antioxidant activity. Six compounds (3, 8, 10, 17, 18 and 19) were found to exhibit significant NO inhibitory activity in LPS/IFN-induced RAW 264.7 macrophages, of which compound 10 demonstrated the highest activity with the IC50 value of 4.2 ± 0.2 μM. Furthermore, two compounds (10 and 17) displayed antioxidant activity upon both the DPPH scavenging and FRAP analyses. However, none of the 2-benzoyl-6-benzylidenecyclohexanone analogs significantly scavenged NO radical. Structure-activity comparison suggested that 3,4-dihydroxylphenyl ring is crucial for bioactivities of the 2-benzoyl-6-benzylidenecyclohexanone analogs. The results from this study and the reports from previous studies indicated that compound 10 could be a candidate for further investigation on its potential as a new anti-inflammatory agent.

Keywords: 2-Benzoyl-6-benzylidenecyclohexanone; Anti-inflammatory; Antioxidant; RAW 264.7; Stability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / analysis*
Antioxidants / chemistry
Benzylidene Compounds / chemical synthesis
Benzylidene Compounds / chemistry
Benzylidene Compounds / pharmacology
Cell Survival / drug effects
Curcumin / chemistry*
Cyclohexanones / chemical synthesis
Cyclohexanones / chemistry
Cyclohexanones / pharmacology*
Humans
Inhibitory Concentration 50
Macrophages / drug effects*
Mice
Microsomes, Liver / drug effects
Nitric Oxide / antagonists & inhibitors*
Pentanoic Acids / chemistry
Pentanoic Acids / pharmacology
RAW 264.7 Cells
Structure-Activity Relationship

Substances

Antioxidants
Benzylidene Compounds
Cyclohexanones
Pentanoic Acids
Nitric Oxide
cyclohexanone
Curcumin