3D-QSAR studies on 4-Hydroxyphenylpyruvate Dioxygenase inhibitors by comparative molecular field analysis (CoMFA)

Meilan Huang, D-Y. Yang, Zhicai Shang, J. Zou, Q. Yu

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)2271-2275
Number of pages5
JournalBioorganic & Medicinal Chemistry
Volume12 (17)
Issue number17
DOIs
Publication statusPublished - 02 Sep 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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