Synthesis and in vitro urease inhibitory activity of 5-nitrofuran-2-yl-thia-diazole linked to different cyclohexyl-2-(phenylamino)acetamides, in silico and kinetic studies

A series of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides were rationally designed and synthesized. All synthetic compounds were evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC50 values in the range of 0.94 - 6.78 mu M as compared to the standard thiourea (IC50 = 22.50 mu M). Compound 8g (IC50 = 0.94 mu M) with a thiophene substituent at the R-2 position was found to be the most active member of the series. Kinetic studies exhibited that the compound 8g was a non-competitive inhibitor. In silico study showed the critical interactions of potent inhibitors with the active site of the enzyme. These newly identified inhibitors of the urease enzyme can serve as leads for further research and development.