Abstract
We designed and synthesized AHI4 that has an axial hydroxyl group instead of geminal methyl groups at C-6' of AHI1, previously reported as a lead compound for the development of non-azole inhibitors of ABA 8'-hydroxylase. (+)-AHI4 competitively inhibited 8'-hydroxylation of ABA by recombinant CYP707A3. The K(I) value was found to be 0.14 microM, 10-fold less than that of (+)-AHI1, suggesting that enzyme affinity increased by a factor of 10 due to substitution of the hydroxyl group by the geminal methyls at C-6'. This finding should assist in the design of more effective, non-azole ABA 8'-hydroxylase inhibitors.
MeSH terms
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Azoles / chemistry
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Azoles / pharmacology
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Cytochrome P-450 Enzyme Inhibitors*
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Cytochrome P-450 Enzyme System / metabolism
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Hydroxylation
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Methylation
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Mixed Function Oxygenases / antagonists & inhibitors*
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Mixed Function Oxygenases / metabolism
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Molecular Structure
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Oryza / drug effects
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Oryza / enzymology
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Plant Proteins
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Seedlings / drug effects
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Seedlings / enzymology
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Water
Substances
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Azoles
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Cytochrome P-450 Enzyme Inhibitors
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Enzyme Inhibitors
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Plant Proteins
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Water
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Cytochrome P-450 Enzyme System
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Mixed Function Oxygenases
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abscisic acid 8'-hydroxylase