72.アゾール環修飾による高選択性アゾール系植物P450阻害剤の創製(口頭発表)

概要

論文の詳細を見る
Uniconazole (UNI), which is well known as a triazole-containing inhibitor of GA biosynthetic enzyme (CYP701A), functions as inhibitors of multiple P450 enzymes including ABA 8'-hydroxylase (CYP707A), which is a key enzyme for ABA catabolism. Azole-containing P450 inhibitors bind to a P450 active site by both coordinating to the heme-iron atom via sp2 nitrogen and interacting with surrounding protein residues through the lipophilic region. We speculated that poor selectivity of UNI may be resulted from its small and flexible conformation adjustable for a variety of substrate pockets. Based on this speculation, we designed and synthesized novel UNI analogues with a disubstituted azole ring (DSI). These analogues were expected to have higher selectivity than UNI because the added functional group may have an interaction with the active site to increase a rigidity of the molecule in the active site. DSI-505M, which has an imidazolyl group with a methyl 5-acrylate at C2, strongly inhibited recombinant CYP707A3, whereas it did not inhibit the growth of rice seedlings.
2009-10-06