Synthesis, Antioxidant and Anti-inflammatory Properties of an Apocynin- Derived Dihydrocoumarin
| Autor: | Luiz Carlos da Silva Filho, Valdecir Farias Ximenes, Luiz Marcos da Fonseca, Aloisio de Andrade Bartolomeu, Maria Luiza Zeraik, Luana Chiquetto Paracatu, Luiza de Carvalho Bertozo |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Antioxidant Erythrocytes medicine.drug_class DPPH Neutrophils medicine.medical_treatment Anti-inflammatory Antioxidants 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship In vivo Coumarins Drug Discovery medicine Humans Enzyme Inhibitors NADPH oxidase biology Dose-Response Relationship Drug Molecular Structure Anti-Inflammatory Agents Non-Steroidal Acetophenones NADPH Oxidases Hydrogen Peroxide Coumarin 030104 developmental biology Biochemistry chemistry Apocynin biology.protein Reactive Oxygen Species Ex vivo |
| Zdroj: | Medicinal chemistry (Shariqah (United Arab Emirates)). 13(1) |
| ISSN: | 1875-6638 |
| Popis: | Background: Coumarin derivatives as dihydrocoumarins have been reported to have multiple biological activities, such as antioxidant and anti-inflammatory properties. Apocynin (APO), which is a substituted-methoxy-catechol, is the most commonly used inhibitor of the multienzymatic complex NADPH-oxidase. Objective: To increase the potency of APO as an NADPH oxidase inhibitor and its antioxidant and anti-inflammatory activities, we synthesized a compound by combining the structural features of a dihydrocoumarin and APO. Method: The dihydrocoumarin-apocynin derivative (HCA) was synthesized and evaluated in antioxidant and cell-based bioassays and compared with APO. Results: We found that HCA (IC 50 = 10 µ M) acted as an inhibitor of NADPH oxidase (ex vivo assays) and was more potent than APO (EC 50 > 10 µM). The inhibitory effect on NADPH oxidase was not related to simple radical scavenger activity. HCA was also a more effective radical scavenger than APO, as verified in the DPPH (EC 50 = 50.3 versus EC 50 > 100 µ M), triene degradation (slope AUC/concentration 759 ± 100 versus 101 ± 15) and FRAP (slope 0.159 versus 0.015) assays. The tested compound demonstrated a similar activity as an inhibitor of the oxidative damage provoked by peroxyl radicals in erythrocyte membranes. Conclusion: HCA showed superior capacity as inhibitor of NADPH oxidase and antioxidant activity. These findings show that HCA could be an improved substitute for APO and deserves further in vivo anti-inflammatory studies. |
| Databáze: | OpenAIRE |
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