抄録
S-Uniconazole (UNI), which was developed as an inhibitor of GA biosynthetic enzyme (CYP701A), is a low selective P450 inhibitor that inhibits multiple P450 enzymes including ABA 8'-hydroxylase (CYP707A). Based on our speculation that the low selectivity of S-UNI may be resulted from its small molecule, we developed enlarged UNI analogues to find a selective inhibitor of CYP707A. Finally we found a practical inhibitor of CYP707A, (±)-abscinazole-E2B (Abz-E2B). (±)-Abz-E2B showed strong inhibitory activity (inhibition constant, K_1=36 nM) against CYP707A, which was equivalent to that of S-UNI (K_1=10 nM). The (±)-Abz-E2B-sprayed plants exhibited drought tolerance, stomatal closure, and an increase in the amount of ABA. On the other hand, against CYP701A, Abz-E2B was a poorer inhibitor, and it did not inhibit the growth of rice seedlings, contrary to UNI. In this study, we optically resolved (±)-Abz-E2B and determined the absolute configuration. The K_1 values of S-(-)- and R-(+)-Abz-E2B for CYP707A were 28 nM and 360 nM, respectively. The similar tendency is observed in UNI whose S-enantiomer is more potent than the R-enantiomer. Similarly, in bioassays, Abz-E2B enhanced the effect of ABA in the order of potency: the S-enantiomer, racemic form, and R-enantiomer. Because no side effects were observed by administration of R-enantiomer, the use of the racemic form may be a reasonable alternative option in the field experiments using a large amount of chemicals.
