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

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5226-9. doi: 10.1016/j.bmcl.2005.08.042. Epub 2005 Sep 16.

Abstract

(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscisic Acid / analogs & derivatives*
  • Abscisic Acid / chemical synthesis
  • Abscisic Acid / chemistry
  • Abscisic Acid / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • Plant Proteins

Substances

  • 6-nor-2',3'-dihydro-4'-deoxoabscisic acid
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Plant Proteins
  • Abscisic Acid
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • abscisic acid 8'-hydroxylase