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

Autor(es)

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.

• Tipo de documento: Artigo Científico
• Fonte: Medicinal Chemistry; v. 13, n. 1, p. 93-100, 2017.
• Citações Web of Science: 4

Resumo

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)

• Processo FAPESP: 10/52327-5 - Prospecção de moléculas bioativas e estudo de variabilidade infra-específica em plantas e microorganismos endófitos do cerrado e caatinga: contribuição para o conhecimento e uso sustentável da biodiversidade brasileira
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