Keywords
Abstract
The purpose of the study was to conduct the comparative analysis of the features of the supramolecular interaction of triazolo-azepine derivatives with cyclooxygenase (СОХ-1 and СОХ-2), and to determine their prospects as potential NSAIDs.
Features of the supramolecular interaction of triazolo-azepine derivatives as COX inhibitors were determined by the binding free energy, geometrical characteristics of the ligands, and specific environment of the molecules by amino acid residues in the active site of COX-2 and COX-1 binding.
Derivatives of triazolo-azepine are located in the active site of COX binding, which is typical for molecules of celecoxib with COX-2 and diclofenac, mofezolac, celecoxib with COX-1, respectively. Triazolo-azepines are placed in the active site of COX binding in the presence of amino acid residues, which are typical for the molecules of comparison drugs. The key interaction of triazolo-azepine derivatives is the position of the ligand and its binding to Arg499 residue in a separate cavity, as it is inherent to celecoxib. The binding energies of the investigated complexes are comparable to drugs.
Availability of characteristic additional zones with Arg499, Ala502, Ile503, Phe504 residues in complexes of triazolo-azepines with COX-2 allows us to predict the mechanism of their anti-inflammatory action which can be mediated through interaction with COX-2.