Evaluation of hepatotoxic properties of pyrimidine derivatives

Abstract

The aim of the study was to evaluate the hepatotoxic properties of new pyrimidine derivatives 3-[2-(1-naphthyl)-2- oxoethyl]-6-bromoquinazoline-4(3H)-oh (VMA–13–06), 3-(2-tert-butyl-2-oxoethyl)quinazoline-4(3H)-one (VMA-13- 11) and 3-(2-isopropyloxy-2-oxoethyl)quinazoline-4(3H)-oh (VMA-13-12). Material and methods. The study was carried out on male rats, which were divided into four groups: control receiving an intragastrically distilled water and experimental groups of animals receiving intragastrically suspended in distilled water pyrimidine compounds VMA- 13-06, VMA-13-11 and VMA-13-12 at doses of 1/10 of the molecular weight (39, 24 and 24 mg/kg respectively) for 60 days. In order to assess possible toxic damage to the liver, blood biochemical parameters were evaluated: alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase activity, total protein, albumin, total and free bilirubin content. Results. There were no statistically significant changes in total protein, albumin, total and free bilirubin after administration of VMA–13–06 and VMA–13–11 in comparison with the control group. The VMA–13–12 compound contributed to an increase in total and free bilirubin content by 43 % (p < 0.01) and 90 % (p < 0.01), while the increase in the concentration of total protein and albumin did not have any statistical significance. The analysis of enzyme parameters also indicates the absence of hepatocyte damage with the introduction of VMA- 13-06 and VMA-13-11: alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase activity did not change. VMA–13–12 administration led to an increase in enzyme activity in comparison with the control: alanine aminotransferase – by 59 % (p < 0.01), aspartate aminotransferase – by 28 % (p < 0.05), gamma- glutamyltransferase – by 46 % (p < 0.01), alkaline phosphatase – by 31 % (p < 0.05). Conclusions. We established the absence of hepatotoxic properties of pyrimidine derivatives 3-[2-(1-naphthyl)-2-oxoethyl]-6-bromoquinazoline-4(3H)- oh and 3-(2-tert-butyl-2-oxoethyl)quinazoline-4(3H)-oh. Compound 3-(2-isopropyloxy-2-oxoethyl)quinazoline-4(3H)- oh has a hepatotoxic effect, accompanied by a decrease in protein-synthesizing and detoxifying liver function.

Keywords

• pyrimidine derivatives
• toxicity
• hepatotoxicity
• biochemical parameters.