Peculiarities of the supramolecular interaction of 5,6,7,8-tetrahydro-2,2a,8atriazacyclopenta[cd]azulene derivatives with cyclooxygenase-2 and arachidonat5-lipoxygenase in the context of anti-inflammatory and antitumor ef

Abstract

The purpose of the study was to research the features of supramolecular interactions of
triazacyclopenta[cd]azulene derivatives with COX-2 and ALOX5 by docking analysis and to determine
the prospects of these compound as potential drugs with a target-dependent mechanism of action.
The peculiarities of complexation of macromolecules with ligands were studied and the results were
compared with the characteristics of comparison ligand complexes. There were determined the free
binding energy and repulsion of the ligands with amino acid residues in protein binding sites: active,
adjacent and separate.
It was found that the active binding sites of the studied compounds are surrounded by amino acid
residues characteristic of the corresponding reference ligands. So, the complexes of the studied and
comparison ligands were comparable.
According to the results of in vivo studies (carrageenan edema), triazacyclopenta[cd]azulenes
showed an anti-inflammatory effect that is comparable to or exceeds the effect of the comparison drug
(diclofenac natrium).
Azulenes at a concentration of 10–5 M showed a high level of antitumor activity in vitro, in particular,
by inhibiting growth of cancer cells of different lines.
Thus, the results of docking analysis, in vitro and in vivo studies determined the prospects of
triazacyclopenta[cd]azulene derivatives as potential inhibitors of COX-2 and ALOX5, candidates for
drugs with anti-inflammatory and antitumor effects.