Structure-activity relationship of a neurite outgrowth-promoting substance purified from the brown alga, Sargassum macrocarpum, and its analogues on PC12D cells

The structure-activity relationship of a neurite outgrowth-promoting substance (designated as MC14) from the brown alga, Sargassum macrocarpum, was analysed. Eight synthetic carotenoids and 1,4-benzoquinone were used to determine the moiety of the MC14 molecule structurally responsible for the nerve growth factor (NGF)-mediated neurite outgrowth-promoting activity on PC12D cells. The bioassays showed that none of these carotenoids exhibited NGF-potentiating activity. In contrast, 1,4-benzoquinone enhanced significantly NGF-mediated neurite outgrowth from PC12D cells, there being a 260% increase over the activity of negative control (10 ng mL(-1) NGF). The effect of quinone structure on NGF-potentiating activity, when examined using 12 naturally occurring quinones, demonstrated that lawsone, alizarin and lapachol significantly enhanced NGF-mediated neurite outgrowth by 329%, 325% and 265%, respectively, of that in the negative control. These results show that quinone is the structural moiety of MC14 molecule responsible for the neurite outgrowth-promoting activity. In addition, the hydroxyl group bonded to quinone had a significant effect on neuritogenic activity. The bearing of a hydroxyl group at the 1'-position of benzoquinone, and the bearing of two hydroxyl groups at the 1' and 2'-positions of anthraquinone, played a crucial role in enhancing the neurite outgrowth-promoting action of NGF.