3D-QSAR studies on 4-hydroxyphenylpyruvate dioxygenase inhibitors by comparative molecular field analysis (CoMFA).
A comparative molecular field analysis (CoMFA) of alkanoic acid 3-oxo-cyclohex-1-enyl ester and 2-acylcyclohexane-1,3-dione derivatives of 4-hydroxyphenylpyruvate dioxygenase inhibitors has been performed to determine the factors required for the activity of these compounds. The substrate's conformation abstracted from dynamic modeling of the enzyme-substrate complex was used to build the initial structures of the inhibitors. Satisfactory results were obtained after an all-space searching procedure, performing a leave-one out (LOO) cross-validation study with cross-validation q(2) and conventional r(2) values of 0.779 and 0.989, respectively. The results provide the tools for predicting the affinity of related compounds, and for guiding the design and synthesis of new HPPD ligands with predetermined affinities.
Huang
Meilan
M
Department of Chemistry, Zhejiang University, Hangzhou, People's Republic of China.
Yang
Ding-Yah
DY
Shang
Zhicai
Z
Zou
Jianwei
J
Yu
Qingsen
Q
D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004952:Esters; D007659:Ketones; D008958:Models, Molecular; D010667:Phenylpyruvic Acids; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D004791:Enzyme Inhibitors; D004952:Esters; D007659:Ketones; D010667:Phenylpyruvic Acids; C010590:4-hydroxyphenylpyruvic acid; D015111:4-Hydroxyphenylpyruvate Dioxygenase