We herein report a facile and high yielding protocol for silica-supported heterogeneous catalysts-mediated synthesis of chalcones. A comparison of results of our synthesis with conventional synthetic protocols is also being offered to assess the efficiency of the prepared catalysts. Biological evaluation of the newly synthesized compounds as urease inhibitors was performed. Most of the compounds were found to have potent urease inhibition activity. The chalcone 3-(3-hydroxyphenyl)-1-phenylpropenone was found to be the most potent with percentage inhibition 86.17 +/- 0.89 and half maximal inhibitory concentration (IC50) value 11.51 +/- 0.03 mu M. The molecular docking study emphasized that the same congeners 3-(furan-2-yl)-1-(4-hydroxyphenyl)propenone, 3-(4-hydroxyphenyl)-1-(4-methoxyphenyl)propanone, and 3-[4-(dimethylamino)phenyl]-1-(p-tolyl)propenone showed very good inhibitory potential against urease and show a higher docking scores 5718, 5940, 5596 and an ACE of - 246.66, - 244.79, and - 243.06 kJ/mol, respectively than the control ligand.