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


METHODS
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.


CONCLUSIONS
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.
Luana C
LC
Paracatu
Maria L
ML
Zeraik
Luiza de Carvalho
LC
Bertozo
Aloisio de Andrade
AA
Bartolomeu
Luiz C da Silva
LCDS
Filho
Luiz M da
LMD
Fonseca
Department of Chemistry, Faculty of Sciences, São Paulo State University (UNESP), P. O. Box 473, 17033-36, Bauru, São Paulo, Brazil.. Brazil.
Valdecir F
VF
Ximenes
D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015394:Molecular Structure; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003374:Coumarins; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; C056165:acetovanillone; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; C026308:3,4-dihydrocoumarin
NADPH oxidase; antioxidant.; apocynin; coumarin; neutrophils