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

[ Vol. 13 , Issue. 1 ]


Luana C. Paracatu, Maria L. Zeraik, Luiza de Carvalho Bertozo, Aloisio de Andrade Bartolomeu, Luiz C. da Silva Filho, Luiz M. da Fonseca and Valdecir F. Ximenes   Pages 93 - 100 ( 8 )


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 µ M) 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 EC50 > 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.


NADPH oxidase, apocynin, coumarin, neutrophils, antioxidant.


Department of Chemistry, Faculty of Sciences, São Paulo State University (UNESP), P. O. Box 473, 17033-36, Bauru, São Paulo, Brazil.

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