Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors

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Title:	Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors
Authors:	Wu, C.-S., Huang, J.-L., Sun, Y.-S., Yang, D.-Y.
Contributors:	Department of Chemistry, Tunghai University
Date:	2002
Issue Date:	2013-05-14T09:03:56Z (UTC)
Abstract:	A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1 -9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations between the results of enzyme inhibition, ferric chloride tests, and the conformational analysis suggested that the tight binding between triketonetype inhibitors and 4-HPPD is likely due to chelation of the enzyme-bound ferric iron with the enol tautomer of 1,3-diketone moiety of the triketones. The presence of a 2-carbonyl group in the triketone is an essential structural feature for potent 4-HPPD inhibition. Modification of the 3-carbonyl group of triketone moiety to other functionality will reduce the overall planarity and thus prevent keto-enol tautomerization, resulting in a decrease or lack of inhibition activity.
Relation:	Journal of Medicinal Chemistry Volume 45, Issue 11, 23 May 2002, Pages 2222-2228
Appears in Collections:	[化學系所] 期刊論文

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