1. Synthesis, Antioxidant and Anti-inflammatory Properties of an Apocynin- Derived Dihydrocoumarin.
- Author
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Paracatu LC, Zeraik ML, Bertozo LC, Bartolomeu AA, Filho LCDS, Fonseca LMD, and Ximenes VF
- Subjects
- Acetophenones chemical synthesis, Acetophenones chemistry, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Antioxidants chemical synthesis, Antioxidants chemistry, Coumarins chemical synthesis, Coumarins chemistry, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Erythrocytes drug effects, Erythrocytes metabolism, Humans, Hydrogen Peroxide metabolism, Molecular Structure, NADPH Oxidases metabolism, Neutrophils drug effects, Neutrophils metabolism, Reactive Oxygen Species metabolism, Structure-Activity Relationship, Acetophenones pharmacology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Antioxidants pharmacology, Coumarins pharmacology, Enzyme Inhibitors pharmacology, NADPH Oxidases antagonists & inhibitors
- Abstract
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 (IC50 = 10 µM) acted as an inhibitor of NADPH oxidase (ex vivo assays) and was more potent than APO (EC50 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 (EC50 = 50.3 versus EC50100 µM), 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2016
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