115128-99-9Relevant academic research and scientific papers
Mode of action of 4-hydroxyphenylpyruvate dioxygenase inhibition by triketone-type inhibitors
Wu, Chung-Shieh,Huang, Jian-Lin,Sun, Yang-Sheng,Yang, Ding-Yah
, p. 2222 - 2228 (2002)
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.
