A lead compound for the development of ABA 8′-hydroxylase inhibitors

[摘要] (1'S*,2'S*)-(+/-)-6-Nor-2',3'-dihydro-4'-deoxo-ABA (2) was designed and synthesized as a candidate lead compound for developing a potent and specific inhibitor of ABA 8'-hydroxylase. This compound acted as an effective competitive inhibitor of the enzyme, with a K-I value of 0.40 mu M, without exhibiting ABA activity. However, compound 2 also functioned as an enzyme substrate, making it a short-lived inhibitor. The 8'-difluorinated derivative of 2 (4) was synthesized as a long-lasting alternative. Compound 4 resisted 8'-hydroxylation, but inhibited ABA 8'-hydroxylation as effectively as 2. These results suggest that compound 2 is a useful lead compound for the future design and development of an ideal ABA 8'-hydroxylase inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.

[发布日期] 2005-12-01

[关键词] abscisic acid;ABA;cytochrome P450;ABA 8'-hydroxylase;inhibitor