Evaluation of the anti-inflammatory activity of a new 1,6-dihydropyrimidine derivative

Introduction. Compounds based on the 1,3-diazine cycle have different types of biological activity. Many of them have shown themselves to good advantage in the pharmaceutical market as effective and safe medicines. The production of new compounds based on the pyrimidine core and the study of their biological activity are an urgent area. Objective: to evaluate the in silico and in vivo acute toxicity and anti-inflammatory activity of 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-sodium olate. Material and methods. The acute toxicity of the test compound was predicted using the local version of the GUSAR software. In vivo acute toxicity was determined in outbred male albino mice. Computer-aided screening of biological activity was performed using the PASS program located on a web service that was freely available via the Internet. Two models (a murine formalin-induced paw edema model and a rat cotton pellet-induced granuloma model) were included in the study to experimentally evaluate anti-inflammatory activity. Results. Predicted and experimental data on acute toxicity correlate with each other. The test compound belongs to the class of practically non-toxic ones. Biological activity screening with the PASS program yielded data on putative anti-inflammatory activity. Studies of in vivo anti-inflammatory activity showed that 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-sodium olate had a pronounced anti-inflammatory activity. Conclusion. The results of computer simulation could determine the acute toxicity of the new 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-sodium olate and identify its potential biological activity. It has been experimentally proven that the test compound has low toxicity and exhibits a pronounced anti-inflammatory activity.

water-soluble pyrimidines, computer-assisted prediction, acute toxicity, anti-inflammatory activity, formalin-induced edema, granuloma