A lead compound for the development of ABA 8'-hydroxylase inhibitors.
(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 0.40microM, 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.
Ueno
Kotomi
K
The United Graduate School of Agricultural Science, Gifu University, Gifu 501-1193, Japan.
Yoneyama
Hidetaka
H
Saito
Shigeki
S
Mizutani
Masaharu
M
Sakata
Kanzo
K
Hirai
Nobuhiro
N
Todoroki
Yasushi
Y
D000040:Abscisic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010940:Plant Proteins
C507186:6-nor-2',3'-dihydro-4'-deoxoabscisic acid; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010940:Plant Proteins; D000040:Abscisic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C107203:abscisic acid 8'-hydroxylase