Evaluation of the Antistaphylococcal Activity of the Pyrimidine Derivative
Authors: Tsibizova A. A. , Yasenyavskaya A. L. , Tyurenkov I. N. , Ozerov A. A. , Baskina O. A. , Samotrueva M. A. 
Published: September 2023

Introduction. The development of safe and effective drugs with antimicrobial activity is currently a priority task of modern pharmacology. The need to obtain new antimicrobial agents is associated with the presence of problems, the main of which is the development of polyresistance of the pathogenic pathogen to existing antibacterial drugs. Of particular interest as a basis for the creation of drugs are pyrimidine compounds, which have a wide range of pharmacological effects, namely psycho- and neurotropic, metabolic, anti-inflammatory, antioxidant, antitumor, immunotropic, etc. Also, the advantage of pyrimidines is the simplicity of the synthesis of new compounds based on them by attaching various functional groups to the heterocycle.

Aim. Evaluation of antistaphylococcal activity of a new pyrimidine derivative in vitro and in vivo.

Materials and methods. Antistaphylococcal activity of pyrimidine derivative 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazolin-4(3H)-oh (VMA-13-13) was studied in vitro using a test culture of a strain of Staphylococcus aureus (Staphylococcus aureus) using the method of serial dilutions. St. aureus was isolated from the sputum of patients treated in inpatient conditions of GBUZ JSC "City Clinical Hospital No. 3 named after S. M. Kirov" (Astrakhan). The minimum suppressive concentration (MPC) of 2-Methyl-3-(2-phenyl-2-oxoethyl) was determined in the studyquinazoline-4(3H)-oh in relation to St. aureus. In vivo, antimicrobial activity studies were conducted on a model of generalized infection caused by intraperitoneal administration of 1 ml of St. aureus drug containing 1 × 108 CFU/ml to mice. Laboratory animals were divided into several groups: control I – animals receiving an equivalent volume of water for injection; control II – animals infected with St. aureus; experimental groups – receiving the comparison drug ceftriaxone (Biosynthesis JSC, Russia) at an average therapeutic dose of 50 mg/kg; and mice treated with a pyrimidine derivative mixed with water for injection, at a dose of 1/10 of the molecular weight of 27 mg/kg, starting from the day of infection for 7 days. The study evaluated the effect of pyrimidine derivative on animal survival. At the end of the experiment, the index of contamination of blood, spleen, liver and lungs was calculated.

Results and discussion. In the study, it was found that the MPC of ceftriaxone, in which this drug had bacteriostatic activity against the St. aureus strain, corresponded to 1 mcg/ml, whereas for the pyrimidine derivative VMA-13-13, the MPC was 16 mcg/ml; the bactericidal effect of the comparison drug was caused at a minimum concentration of 32 mcg/ml, and the substance under study is in a concentration of 64 micrograms/ml. The formation of generalized staphylococcal infection led to a decrease in the survival rate of animals in the untreated control group up to 30 %; with the introduction of ceftriaxone and pyrimidine derivative – up to 80 % compared with the intact control. When evaluating the antistaphylococcal activity of pyrimidine derivative in the untreated control group, in comparison with the intact control, an increase in the index of bacterial contamination of internal organs and blood was observed. The introduction of ceftriaxone and the compound VMA-13-13 led to a decrease in this indicator in the lungs and blood by 6.6 (p ≤ 0.01) times compared with the infected group of animals; staphylococcus was not sown in the liver and spleen.

Conclusion. Thus, it was established that the compound of pyrimidine nature is 2-Methyl-3-(2-phenyl-2-oxoethyl)quinazoline-4(3H)-it has a bactericidal effect against Staphylococcus aureus and helps to increase the survival rate of laboratory animals in conditions of generalized staphylococcal infection.