Synthesis and biological evaluations of novel apocynin analogues

We have designed and synthesized a series of novel apocynin analogues, and evaluated their biological activity. Compound 10, an apocynin dimer analogue, compound 12, the lipoic acid (LA) and apocynin conjugate, were the most potent in protecting cells from lipopolysaccharide (LPS)-induced cytotoxicity, had significant activity scavenging ROS induced by LPS, and greatly decreased LPS-induced P67phox protein expression. SAR analysis suggests that modification of apocynin can increase its activity. Our results demonstrate that arming apocynin with a powerful antioxidant such as lipoic acid is a valid strategy to design new apocynin analogues with enhanced biological activity.

Graphical abstractThe synthesis and biological evaluations of novel apocynin analogues suggests that structure modification of apocynin can increase its biological activity. Compounds 10–12, the derivatives of apocynin, show promising biological activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of novel apocynin analogues was synthesized and biologic activity evaluated. ► Compounds 10 and 12 were the most potent and greatly decreased P67phox expression. ► Modification of apocynin with short chain substituent can increase biologic activity.