Computer prediction and verification of antioxidative activity of exo-functionalized derivatives of 9,10-antraquinone.

: 83-91
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University
Lviv Polytechnic National University

A computer-aided prediction of the pharmacological activity of a number of exo-functionalized derivatives of 9,10-anthraquinone with amino acid and thiazole fragments for the search of compounds with antioxidant effect using the program PASS of the web resource Way2Drug was carried out. The obtained results were analyzed for the probability of the mechanism of antioxidant action as a radical scavenger, antihypoxic, oxygen scavenger, radical formation agonist and catalase stimulator. Experimental testing of selected derivatives in in vitro hepatocyte studies on the ability of peroxide oxidation of lipids (POL) was carried out by determining the content of thiobarbituric (TBC-active) products. The oxidative modification of the protein (OMP) was determined by the number of formed additional carbonyl groups (CG) in the side chains of proteins. The obtained results of the conducted studies using in silico and in vitro methods allowed to identify promising substances, namely, derivatives of 9,10-anthraquinone 2a, 2б, 2e with the expressed antioxidant activity in two indices of oxidative stress of the POL and OMP in comparison with the control and known antioxidant quercetin. It has been experimentally determined that N-functionalization with acylamino acid and thiazole residues in some cases allows to reduce the formation of active forms of oxygen (AFO) and the free radical processes initiated by them. Some correlations were found between the structure and the effect of the investigated compounds. In particular, it was found that modifying of the amino group of 9,10-anthracenedione with the N-acyl moiety containing alanine, phenylalanine, leucine, methionine, γ-aminobutyric acid residues the effect of the chain acid linearity and the amount of methylene linkages between the carboxylic and amino groups is significant for the antioxidant effect of amino acid molecule. The re-functionalization of the amino group of 9,10-anthracenedione with the thiazole ring in the presence of the NH2-group at position 4 leads to an increase of the antioxidant effect and its approximation to quercetin. The conducted studies are important for medical chemistry, since they allow to identificate the most promising compounds with a pronounced antioxidant or no effect on the metabolism of cells and the body as a whole. The presence of antioxidant properties of the investigated compounds allows to be considered as potential objects for further research, in particular as antithrombotic and antitumor substances.

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