Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed EsterAmide-Based Derivatives as Jack Bean Urease Inhibitors

Abstract EN

A series of halo-substituted mixed ester/amide-based analogues 4a-l 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 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a–f to prepare the title compounds 4a-l.

The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra.

The compound 4b showed remarkable activity with IC501.6±0.2 nM, better than the standard thiourea having IC50472.1±135.1 nM.

The 2-chloro-substituted phenyl ring on one side of compound 4b 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 4b derivative as a mixed type of inhibitor.

The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of −7.8 and −7.9 Kcal/mol, respectively.

Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea.