Abstract
This study deals with efficient epoxidation of (E)-1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (1) with hydrogen peroxide to afford the corresponding epoxide derivative 2, which was allowed to react with either urea or thiourea to afford the corresponding tetrahydropyrimidine-2.5-dione and/or 2-thioxo tetrahydropyrimidin-5(6H)-one compounds 3, 4, respectively. The latter derivatives 3 and 4 were utilized as key precursors for preparation of a new set of tetrahydropyrimidine nucleosides via N- and/or S-glycosidic linkages and different Schiff s bases. These hybrid compounds were evaluated as H5N1 avian influenza A virus inhibitors. N-nucleoside analog 8 and the indolo-Schiff's base 22 demonstrated the most potent antiviral activity showing 71.76% viral inhibition. Molecular modeling studies revealed that compounds 8 and 22 exhibited effective fitting in the active site. good binding mode and reasonable docking scores with RNA polymerase protein that might explain their effective antiviral potency and represent them as new promising antiviral scaffolds for further developing and optimization.