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

Abstract

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. 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. The dihydrocoumarin-apocynin derivative (HCA) was synthesized and evaluated in antioxidant and cell-based bioassays and compared with APO. 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. 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.