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

被引：10

作者：

Ueno, K

Yoneyama, H

Saito, S

Mizutani, M

Sakata, K

Hirai, N

Todoroki, Y ^{[1
]}

机构：

[1] Shizuoka Univ, Fac Agr, Dept Appl Biol Chem, Shizuoka 4228529, Japan

[2] Gifu Univ, United Grad Sch Agr Sci, Gifu 5011193, Japan

[3] Kyoto Univ, Inst Chem Res, Uji, Kyoto 6110011, Japan

[4] Kyoto Univ, Int Innovat Ctr, Kyoto 6068501, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 23期

基金：

日本学术振兴会;

关键词：

abscisic acid; ABA; cytochrome P450; ABA 8'-hydroxylase; inhibitor;

D O I：

10.1016/j.bmcl.2005.08.042

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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.

引用

页码：5226 / 5229

页数：4

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