Abstract
A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC 50 = 2.45 μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase.
Original language | English |
---|---|
Pages (from-to) | 5569-5576 |
Number of pages | 8 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 19 |
Issue number | 18 |
DOIs | |
Publication status | Published - Sept 15 2011 |
Externally published | Yes |
Keywords
- Molecular docking
- N-(1,3-Diaryl-3-oxopropyl)amides
- Non-purine xanthine oxidase inhibitors
- Xanthine oxidase
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry