Synthesis and biological assessment of 2-hydroxyiminoethanones as anti-inflammatory and β-amyloid aggregation inhibitors

Document Type: Research article

Authors

1 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

3 Department of Pharmacology & Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sihhiye, 06100 Ankara, Turkey.

Abstract

Alzheimer’s disease (AD) is a neuroinflammatory based pathologic state in which β-amyloid aggregates are a major devastating agents. In this study, a series of 2-hydroxyiminoethanones were synthesized and evaluated as anti-inflammatory in carrageenan and formalin tests and inhibitors of β-amyloid aggregation. Compounds 1-10b were synthesized through a two-step reaction. Results: Compounds 1-5b showed more β-amyloid disaggregation ability than reference drugs rifampicin and donepezil and compound 2b was the best compound in this series and could reduce the extent of amyloid aggregation to 50.9%. Interestingly, compounds 1b and 3b showed significant anti-inflammatory activity in carrageenan-induced paw edema compared to control group and equivalent to the reference drug indomethacin. 2-Hydeoxyiminoethanones are privileged scaffold for further drug research and development as anti-neuroinflammatory and neuroprotective agents.

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