The Influence of New Antitumor Compounds Based on Azoloazine Derivatives on Level of DNA Damage in Normal Vero Cell Line in the DNA Comet Assay.

The purpose of this study was to investigate the effect of new azoloazine derivatives on the level of DNA damage in Vero cells in vitro using alkaline gel electrophoresis (DNA comet assay). The objects of research were (1) 8-(piperidinocarbonyl)-3-cyclohexylimidazo[5,1-d][1,2,3,5]tetrazine-4(3N)-one, (2) 4‑aminoimidazo[5,1-c][1,2,4]triazine-3,8-dicarboxylic acid, and (3) 4-amino-8-ethoxycarbonylimidazo[5,1-c][1,2,4]triazine-3-N-(P-toluyl)carboxamide. Epirubicin was chosen as a comparison drug. Compounds were used in doses of 1/2, 1/10, and 1/50 IC₅₀. The Vero cell line, cultured according to standard protocol was used as the cell model. To assess genotoxicity, an alkaline version of the comet assay, which is highly sensitive and allows the detection of DNA damage was used. Analysis of the obtained data indicates that tested compounds 1–3 increase the amount of DNA damage in nontumor cells. Compound 1 has the most pronounced genotoxic effect. Thus, using this compound at a dose of 1/2 IC₅₀ led to a significant increase in the comet tail length by 1.5 times. It was noted that the amount of DNA damage caused by the action of compound 1 at the studied doses and epirubicin was on the same level. The results obtained show that compounds 1–3 may be potentially carcinogenic. However, this conclusion requires further in-depth experimental stud-ies. [ABSTRACT FROM AUTHOR]