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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis, Antioxidant and Anti-inflammatory Properties of an Apocynin- Derived Dihydrocoumarin

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Paracatu, Luana C. ; Zeraik, Maria L. ; Bertozo, Luiza de Carvalho ; Bartolomeu, Aloisio de Andrade ; da Silva Filho, Luiz C. ; da Fonseca, Luiz M. ; Ximenes, Valdecir F.
Total Authors: 7
Document type: Journal article
Source: Medicinal Chemistry; v. 13, n. 1, p. 93-100, 2017.
Web of Science Citations: 7

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 mu M) acted as an inhibitor of NADPH oxidase (ex vivo assays) and was more potent than APO (EC50 > 10 mu M). 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 EC50 > 100 mu 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. (AU)

FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 13/08784-0 - Kinetic studies of reactions mediated by oxidants produced by neutrophils: mechanism of deleterious action and development of enzyme inhibitors
Grantee:Valdecir Farias Ximenes
Support type: Regular Research Grants