INHIBITORY EFFECT OF PERILLOSIDE-A AND PERILLOSIDE-C, AND RELATED MONOTERPENE GLUCOSIDES ON ALDOSE REDUCTASE AND THEIR STRUCTURE-ACTIVITY-RELATIONSHIPS

Monoterpene glucosides, perilIosides A and C, obtained from the leaves of Perilla frutescens, were found to be inhibitors of aldose reductas e (EC 1.1.1.21) which is considered to be a key enzyme in diabetic com plications such as cataract. The apparent type of inhibition of rat le ns aldose reductase by perillosides A and C was competitive with respe ct to glyceraldehyde and their Ki values were 1.4 x 10(-4) and 2.3 x 1 0(-4) M, respectively. The type of inhibition by their tetraacetates w as non-competitive with respect to the same substrate, although their inhibitory effects were increased by about one order of magnitude comp ared with those of the perillosides and the Ki values were 2.5 x 10(-5 ) and 7.1 x 10(-5) M, respectively. We also prepared related monoterpe ne glucosides and their tetraacetates and determined their inhibitory activities towards aldose reductase in order to elucidate the relation ship between structure and inhibitory activity.