RESEARCH OF HEPATOPROTECTIVE ACTIVITY OF PYRIMIDINE DERIVATIVES IN VITRO

Abstract

The article presents data on experimental study of the hepatoprotective activity of pyrimidine derivatives (5-amino-6-methyluracil, 5-methylamino-6-methyluracil, 1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl N-phtalyl valinate, 5-piperidinomethyl-6-methyluracil, 3-morpholinomethyl-5-nitro-6-methyluracil) by incubation of mouse hepatocytes МН-22а poisoned with carbon tetrachloride. MTT-test was used to determine cell viability. Positive control was cells treated only with carbon tetrachloride (100 mM, 1% DMSO). Among compounds studied in this experiment 5-amino-6-methyluracil (400 µM) and 3-morpholinomethyl-5-nitro-6-methyluracil (50 µM) were the most effective for the survival of liver cells under seeding conditions. The increase in cell survival (relative to the values in the positive control group) under the conditions of tetrachloromethane priming and treatment with these drugs was up to 27,5% (p < 0,05) for 5-amino-6-methyluracil and 22,42% (p < 0,05) for 3-morpholinomethyl-5-nitro-6-methyluracil. The compounds 5-methylamino-6-methyluracil and 1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl N-phtalyl valinate have low toxicity, but did not show antioxidant properties. The derivative 5-piperidinomethyl-6-methyluracil (400 µM) showed high toxicity (30,04 ± 0.90%; p < 0,05) and the survival of the cells treated with carbon tetrachloride was lower or equal to the values of positive control, which does not allow it to be used as an antioxidant.