Structure-activity relationships of anthraquinones in the decrease of intestinal motility

The effects of substituted anthraquinones on intestinal motility were evalu ated in-vitro using rabbit small intestinal strips. This structure-activity relationship study revealed the critical requiremen t of a hydroxy group at R-2 position. The intestinal motility was inhibited 50% (IC50) by emodine (8 mu M), 2-hydroxy anthraquinone (20 mu M), 2,6-dih ydroxy anthraquinone (25 mu M), 2,7-dihydroxy anthraquinone (10 mu M), 1,2, 4-trihydroxy anthraquinone (80 mu M) and 1,2,5,8-tetra-hydroxy-anthraquinon e (9 mu M). The presence of other polar groups at R-2 position such as an a mino, aldehyde and carboxylic acid group significantly reduced the activity (IC50 360-400 mu M). The presence of a methyl group and esterification of the carboxylic acid at R-2 position was found to abolish the activity. These data are useful for the future development of anthraquinones as laxat ive agents.