Affordable Access

Enzyme selectivity of new cyclooxygenase-2/5 lipoxygenase inhibitors using molecular modeling approach.

Authors
  • Kothekar, V
  • Sahi, S
  • Mishra, J
Type
Published Article
Journal
Indian journal of biochemistry & biophysics
Publication Date
Apr 01, 2000
Volume
37
Issue
2
Pages
86–96
Identifiers
PMID: 10983419
Source
Medline
License
Unknown

Abstract

We have studied the conformational flexibility of three 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) which show dual cyclooxygenase (COX) and 5-lipoxygenase (LOX) inhibition and are potential candidates as antiinflammatory agents and analgesics. The conformations were studied by systematic search, molecular mechanics (MM) and simulated annealing molecular dynamics (SAMD) techniques. We also studied several structure based parameters and distribution of molecular electrostatic potential (MEP) around these molecules. All the three compounds were docked in the active cavity of cyclooxygenase-2 (COX-2) using graphical and energy grid search techniques. The complex geometries were optimized by MM. The results on conformational flexibility, inter-atomic distances and angles, MEP distribution and points of contacts with peptide side chains in active cavity have been used to understand the mechanistic cause of differential action of these molecules.

Report this publication

Statistics

Seen <100 times