Novel 4,5-Diaryl-3-hydroxy-2(5H)-furanones as Anti-Oxidants and Anti-Inflammatory Agents
| Autor: | Daniel Gardette, Jean Claude Gramain, M. Madesclaire, Eliane Duroux, Danielle Vallee-Goyet, Pascal Coudert, Fernand Leal, Marc Bria, Jacques Couquelet, Valérie Weber, Eliane Albuisson, Catherine Rubat |
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| Rok vydání: | 2002 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Antioxidant medicine.drug_class Stereochemistry Radical medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis Antioxidants Anti-inflammatory Lipid peroxidation Inhibitory Concentration 50 Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Edema Furans Molecular Biology Inflammation Molecular Structure Superoxide Anti-Inflammatory Agents Non-Steroidal Organic Chemistry Ascorbic acid Rats chemistry Lipophilicity Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 10:1647-1658 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(02)00053-6 |
| Popis: | In order to study the effect of phenol moieties on biological activities of ascorbic acid derivatives, we synthesized 13 novel 4,5-diaryl-3-hydroxy-2(5H)-furanones 5a-m with various substitution patterns. Compound 5 g bearing a 2,3-dihydroxy phenyl ring on the 5-position of the heterocycle appeared to be the most powerful anti-oxidant furanone with reducing activity against DPPH (IC(50)=10.3 microM), superoxide anion quenching capacity (IC(50)=0.187 mM) and lipid peroxidation inhibitory effect (IC(50)=0.129 mM). To ascertain determinant molecular features for anti-oxidant activities, structure-activity relationships were studied. Lipophilicity and molecular parameters related to electron distribution and structure (difference in heats of formation between the compound and its radical or its cation radical, energy of the highest occupied molecular orbital, HOMO) were found to correlate with the anti-oxidant action of compounds 5 in the different tests used. Oxygen-derived free radicals are known to contribute to inflammatory disorders; therefore we have investigated effects of compounds 5 in two models of inflammation: phorbol ester-induced ear edema in mice (TPA-test) and carrageenan-induced paw edema in rat. At 100 mg/kg ip in the TPA-test, the anti-inflammatory activity of compounds 5 was potent compared with that of indomethacin and ketorolac and all the results suggested a cyclooxygenase inhibition in the emergence of such properties. The combined pharmacological actions of compounds 5 associated with a favorable therapeutic index prompt with interesting perspectives for their use in heart and brain disorders as well as in inflammatory diseases. |
| Databáze: | OpenAIRE |
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