Synthesis, Biological Properties, and Docking Study of 5-Substituted 6-Methyl-2-[(E)-2-(aryl)ethenyl]pyrimidin-4(3H)-ones

Objective: By condensation of 5-substituted 2,6-dimethylpyrimidin-4(3H)-ones with aromatic aldehydes, 5-substituted 6-methyl-2-[(E)-2-(aryl)ethenyl]pyrimidin-4(3H)-ones were obtained. By chlorination of 5-pentyl-2-(4-bromophenyl)ethenyl) derivative followed by treatment with dimethylamine, 4-dimethylamino derivative was synthesized, isolated as picrate. Methods: Chemical synthesis. Results and Discussion: The antimicrobial and antifungal properties of the synthesized compounds and known drugs were studied against Staphylococcus aureus and Escherichia coli bacteria and Candida albicans fungus. A docking study was performed against four targets: the RNA-dependent RNA polymerase (RdRp) complex with the NSP7 and NSP8 proteins of the SARS-CoV-2 virus, the kinase domain of the human epidermal growth factor receptor (EGFR), doubly phosphorylated human mitogen-activated protein kinase 14 (MAPK14) in complex with the activator of transcription factor (ATF2), and human monoamine oxidase B in complex with 2-(2-benzofuranyl)-2-imidazoline. (2-BFI). Conclusions: It was shown that the size of the substituent at position 5 of 2-styrylpyrimidines leads to the emergence of significant antifungal activity in the compounds, in the absence of antibacterial activity. Docking studies of the synthesized pyrimidines did not reveal the predicted activity against the used targets, although the obtained ΔGo values are comparable to those for known drugs with a similar pharmacological profile. The obtained results indicate the potential of searching for compounds with antifungal activity in the 2-styrylpyrmidine series.