In silico design and synthesis of N-arylalkanyl 2-naphthamides as a new class of non-purine xanthine oxidase inhibitors
| Autor: | Sheau Ling Ho, Shoei-Sheng Lee, Ching-Ting Lin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Xanthine Oxidase
medicine.drug_class In silico Potassium Allopurinol chemistry.chemical_element Hyperuricemia Pharmacology 03 medical and health sciences chemistry.chemical_compound Mice Structure-Activity Relationship 0302 clinical medicine Oral administration Drug Discovery medicine Animals Enzyme Inhibitors Xanthine oxidase Xanthine oxidase inhibitor IC50 In vitro Molecular Docking Simulation chemistry 030220 oncology & carcinogenesis 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Drug development researchREFERENCES. 82(6) |
| ISSN: | 1098-2299 |
| Popis: | A series of N-arylalkanyl 2-naphthamides (Xa~e), which were predicted from virtual molecular docking on a built xanthine oxidase template as potential inhibitors, were synthesized. Their inhibitory activity against xanthine oxidase was assayed. Among these prepared, compounds Xb (IC50 13.6 μM), Xc (IC50 13.1 μM), and Xd (IC50 12.5 μM) showed comparable inhibitory activity to allopurinol (IC50 22.1 μM). The in vitro assay result correlated well with molecular docking scores, ΔG = -16.99, -17.66, and -17.13 Kcal/mol, respectively. On the potassium oxonate-induced hyperuricemic mice model, oral administration of Xc-Ac (40 mg/ Kg), the per-O-acetylated Xc, could reduce the blood uric acid level by 60% in comparison to the normal control group and is statistically significant (p |
| Databáze: | OpenAIRE |
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