CoMFA of two classes of 4-hydroxyphenylpyruvate dioxygenase inhibitors

Comparative molecular field analysis (CoMFA) was used to perform a quantitative structure-activity relationship study of cyclohexane-1, 3-diones and alkanoic acid 3-oxo-cyclohex-1-enyl analogues as 4-hydroxyphenylpyruvate dioxygenase inhibitors. The structure of the substrate abstracted from the dynamics modelling of the enzyme-substrate complex was used to design the structure of the inhibitors. Satisfactory results 2 were obtained after all-space searching, with the leave-one out cross validation correlation coefficient q(2) = 0.779 and conventional r(2) = 0.989. The model will be used to speculate the combining mode between the inhibitors and the receptor as well as to quantitatively prognosticate the biological activity of analogues. Moreover, it provides theoretical foundation for synthesizing new HPPD inhibitors.