Structure–activity relationship of uniconazole, a potent inhibitor of ABA 8′-hydroxylase, with a focus on hydrophilic functional groups and conformation

The plant growth retardant S-(+)-uniconazole (UNI-OH) is a strong inhibitor of abscisic acid (ABA) 8′-hydroxylase, a key enzyme in the catabolism of ABA, a plant hormone involved in stress tolerance, stomatal closure, flowering, seed dormancy, and other physiological events. In the present study, we...

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Published in:Bioorganic & medicinal chemistry 2008-03, Vol.16 (6), p.3141-3152
Main Authors: Todoroki, Yasushi, Kobayashi, Kyotaro, Yoneyama, Hidetaka, Hiramatsu, Saori, Jin, Mei-Hong, Watanabe, Bunta, Mizutani, Masaharu, Hirai, Nobuhiro
Format: Article
Language:English
Subjects:
ABA
Abscisic acid
Azole
Binding Sites
Biological and medical sciences
Chemical control
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Fundamental and applied biological sciences. Psychology
Growth regulators
Metabolism
Mixed Function Oxygenases - antagonists & inhibitors
Molecular Conformation
P450
Parasitic plants. Weeds
Phytopathology. Animal pests. Plant and forest protection
Plant physiology and development
Static Electricity
Structure-Activity Relationship
Triazoles - chemistry
Triazoles - pharmacology
Uniconazole
Weeds
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Summary:The plant growth retardant S-(+)-uniconazole (UNI-OH) is a strong inhibitor of abscisic acid (ABA) 8′-hydroxylase, a key enzyme in the catabolism of ABA, a plant hormone involved in stress tolerance, stomatal closure, flowering, seed dormancy, and other physiological events. In the present study, we focused on the two polar sites of UNI-OH and synthesized 3- and 2″-modified analogs. Conformational analysis and an in vitro enzyme inhibition assay yielded new findings on the structure–activity relationship of UNI-OH: (1) by substituting imidazole for triazole, which increases affinity to heme iron, we identified a more potent compound, IMI-OH; (2) the polar group at the 3-position increases affinity for the active site by electrostatic or hydrogen-bonding interactions; (3) the conformer preference for a polar environment partially contributes to affinity for the active site. These findings should be useful for designing potent azole-containing specific inhibitors of ABA 8′-hydroxylase.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2007.12.019