Effect of new antitumor compounds based on azoloazine derivatives on the level of DNA damage in normal Vero cells in the DNA comet test

Abstract

The aim of the work is to study the effect of new azoloazine derivatives on the level of DNA damage to Vero cells (DNA comet test) in vitro by alkaline gel electrophoresis.Material and methods. The objects of the study are 8-(piperidinocarbonyl)3-cyclohexylimidazo[5,1-d][1,2,3,5]tetrazine-4(3H)-one (1), diethyl ether 4-aminoimidazo[5,1-c][1,2,4]triazine3,8-dicarboxylic acid (2), 4-amino-8-ethoxycarbonylimidazo[5,1-c][1,2,4]triazine-3-N-(p-toluyl)carboxamide (3). Epirubicin was chosen as a comparison drug. The compounds were used in doses of 1/2, 1/10 and 1/50 IC50. The Vero cell line cultured according to the standard protocol was selected as the cell model. To assess genotoxicity, an alkaline version of the DNA comet method was used, which has a high sensitivity and allows detecting DNA damage.Results. Analysis of the data obtained indicates that the tested compounds 1-3 enhance DNA damage in non-tumor cells. Compound 1 has the most pronounced genotoxic effect. Thus, the use of this substance in a dose of ½ IC50 led to a significant increase in the length of the comet’s tail by 1.5 times. It was noted that DNA damage under the action of compound 1 in the studied doses and of epirubicin was on the same level.Conclusions. The results obtained prove that compounds 1-3 may have a potentially carcinogenic effect. However, this assumption requires further in-depth experimental studies.

Keywords

• azoloazines
• genotoxicity
• vero
• carcinogenic effect