A new non-azole inhibitor of ABA 8′-hydroxylase:: Effect of the hydroxyl group substituted for geminal methyl groups in the six-membered ring

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 mu M, 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. (c) 2006 Elsevier Ltd. All rights reserved.