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NADPH Oxidase Inhibition of Novel Apocynin Dimer Derivatives

Shusheng Wang, Gaofang Wang, Xianyao Fu, Jianbin Qi, Lingchao Zhu, Sha Li, Jie Jiang

Abstract


Apocynin is a widely studied inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which has been regarded as a target for developing anti-oxidative and anti-inflammatory therapeutic agents. Diapocynin, dimer of apocynin, was found to have higher NADPH oxidase inhibition activity than apocynin. To seek for dimeric apocynin analogues of better efficacy, in our previous work, 14 novel apocynin dimer derivatives were designed and synthesized based on the chemical structure of apocynin dimer analogue JJA-D0. The biological activities of the derivatives were evaluated in RAW 264.7 cells. Allcompounds protected RAW 264.7 cells from lipopolysaccharide (LPS)-induced cytotoxicity, and significantly lowered down the intracellular ROS level induced by LPS. JJA-D26 were more potent than apocynin and JJA-D0, which retained 71.2% of cell viability, and decreased 24.8% of intracellular ROS level at the concentration of 200 ?M. JJA-D26 also greatly inhibited the expression of pro-inflammatory cytokine TNF-a, and significantly reduced the expression of subunits p47phox and gp91phox of NADPH oxidase complex (P < 0.05 and P < 0.01 respectively) compared to apocynin. This work may provide useful information for the research and development of potent anti-oxidation and anti-inflammation drugs targeting NADPH oxidase.

Keywords


apocynin dimer derivatives, NADPH oxidase, reactive oxygen species, anti-oxidation, anti-inflammation

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