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

A. H. Al-Humairi, D. L. Speranskiy, M. Y. Minakova, N. Cherdyntseva, V. V. Udut
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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.
基于氮丙嗪衍生物的新型抗肿瘤化合物在 DNA 彗星试验中对正常 Vero 细胞 DNA 损伤水平的影响
这项研究的目的是通过碱性凝胶电泳法研究新型氮丙嗪衍生物对体外 Vero 细胞 DNA 损伤程度(DNA 彗星试验)的影响。研究对象为 8-(哌啶甲酰基)3-环己基咪唑并[5,1-d][1,2,3,5]四嗪-4(3H)-酮(1)、二乙醚 4-氨基咪唑并[5、1-c][1,2,4]三嗪-3,8-二羧酸 (2)、4-氨基-8-乙氧羰基咪唑并[5,1-c][1,2,4]三嗪-3-N-(对甲苯基)甲酰胺 (3)。表柔比星被选为对比药物。这些化合物的 IC50 剂量分别为 1/2、1/10 和 1/50。选择按照标准方案培养的 Vero 细胞系作为细胞模型。为了评估遗传毒性,使用了碱性版 DNA 彗星法,该方法灵敏度高,可检测 DNA 损伤。对所得数据的分析表明,测试的 1-3 号化合物会增强非肿瘤细胞的 DNA 损伤。化合物 1 的基因毒性作用最为明显。因此,使用 IC50 ½ 剂量的这种物质会导致彗尾长度显著增加 1.5 倍。我们注意到,在所研究剂量的化合物 1 和表柔比星的作用下,DNA 损伤程度相同。研究结果证明,化合物 1-3 可能具有潜在的致癌作用。不过,这一假设还需要进一步的深入实验研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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