Enzyme selectivity of new cyclooxygenase-2/5 lipoxygenase inhibitors usingmolecular modeling approach

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 wer e studied by systematic search, molecular mechanics (MM) and simulated anne aling molecular dynamics (SAMD) techniques. We also studied several structu re based parameters and distribution of molecular electrostatic potential ( MEP) around these molecules. All the three compounds were docked in the act ive cavity of cyclooxygenase-2 (COX-2) using graphical and energy grid sear ch techniques. The complex geometries were optimized by MM. The results on conformational flexibility, inter-atomic distances and angles, MEP distribu tion and points of contacts with peptide side chains in active cavity have been used to understand the mechanistic cause of differential action of the se molecules.