Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors.

A series of halo-substituted mixed ester/amide-based analogues have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines reacted with chloroacetyl chloride to afford intermediates , which were then reacted with different halo-substituted benzoic acids to prepare the title compounds . The chemical structures of final products were ascertained by FTIR, H NMR, C NMR, and mass spectra. The compound showed remarkable activity with IC1.6 ± 0.2 nM, better than the standard thiourea having IC472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver-Burk plots (kinetics study) indicated about derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds and have binding energies of -7.8 and -7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative is a highly potent urease inhibitor, better than the standard thiourea.