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-promotingsubstance (designated as MC14) from the brown alga, Sargassummacrocarpum, was analysed. Eight synthetic carotenoids and1,4-benzoquinone were used to determine the moiety of the MC14molecule structurally responsible for the nerve growth factor(NGF)-mediated neurite outgrowth-promoting activity on PC12D cells.The bioassays showed that none of these carotenoids exhibitedNGF-potentiating activity. In contrast, 1,4-benzoquinone enhancedsignificantly NGF-mediated neurite outgrowth from PC12D cells, therebeing a 260% increase over the activity of negative control (10 ngmL^-1 NGF). The effect of quinone structure on NGF-potentiatingactivity, when examined using 12 naturally occurring quinones,demonstrated that lawsone, alizarin and lapachol significantly enhancedNGF-mediated neurite outgrowth by 329%, 325% and 265%,respectively, of that in the negative control. These results show thatquinone is the structural moiety of MC14 molecule responsible for theneurite outgrowth-promoting activity. In addition, the hydroxyl groupbonded to quinone had a significant effect on neuritogenic activity. Thebearing of a hydroxyl group at the 1'-position of benzoquinone, and thebearing of two hydroxyl groups at the 1' and 2'-positions of anthraquinone,played a crucial role in enhancing the neurite outgrowth-promoting actionof NGF.