Authors : Valdecir F. Ximenes , Iguatemy L. Brunetti and Luiz M. da Fonseca
Abstract: Apocynin has been extensively used as a non-toxic inhibitor of the multi-enzyme NADPH oxidase complex in phagocytic and non-phagocytic cells. Here we investigate the potency of apocynin (4-acetylguaiacol) and the related substituted methoxy-catechols, 4-nitroguaiacol, 4-methylguaiacol, 4-ethylguaiacol, 4-cyanoguaiacol and eugenol as inhibitors of NADPH oxidase of neutrophils stimulated by Lipopolysaccharide (LPS) in whole blood. These compounds were chosen as they could reveal the structure-activity relationship between the presence of electron-donating and electron-withdrawing substituents groups on the methoxy-catechol moiety and their effect as NADPH oxidase inhibitor. The whole blood experimental model was chosen as it is close to physiological conditions and could reveal the real potency of these drugs. The NADPH oxidase activation was assessed by the Nitro Blue Tetrazolium (NBT) cytochemical assay. We found that apocynin (methoxy-catechol with an acetyl group) was an efficient NADPH oxidase inhibitor in whole blood. The presence of stronger electron-withdrawing substituents groups, represented by the compounds 4-nitroguaiacol and 4-cyanoguaiacol diminished significantly their potency as NADPH-oxidase inhibitor. However, the presence of electron-donating groups represented by 4-methylguaiacol, 4-ethylguaiacol and eugenol were poor inhibitors compared with the other methoxy-catechols. A correlation was noted between the electron-donating and electron-withdrawing character of the substituent groups and the power to inhibit NADPH oxidase.
Valdecir F. Ximenes , Iguatemy L. Brunetti and Luiz M. da Fonseca , 2007. Apocynin and Related Methoxy-Catechols as Inhibitors of Neutrophil-NADPH Oxidase in LPS-Activated Whole Blood . Research Journal of Biological Sciences, 2: 360-364.