Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Coumarinylthiazolyl Iminothiazolidinone Hybrids as Potent Urease Inhibitors

The present paper is designed to explore the potential of an important class of heterocycles coumarinylthiazolyl iminothiazolidinone to inhibit jack bean urease. The final products 6a – j were prepared by condensation of substituted aldehydes with intermediate 5 in sodium methoxide/methanol mixture. The synthesized compounds were characterized by their FTIR, 1 H, 13 C NMR and mass spectral data. The synthesized coumarinylthiazolyl iminothiazolidinone hybrids 6   a – j were evaluated for their potential to inhibit urease activity. All the synthesized derivatives showed remarkable inhibitory activity with IC 50 ranging 8 to 34 nM, while IC 50 of standard thiourea is 18.5 nM. The compound 5‐(2,4‐Dichlorobenzylidene)‐2‐(4‐(2‐oxo‐2 H ‐chromen‐3‐yl)thiazol‐2‐yl imino) thiazolidin‐4‐one 6   h bearing 2,4‐di‐chloro substituted phenyl ring exhibited excellent activity with IC 50 value 8 nM. In silico molecular docking studies was performed against urease enzyme PDBID 4H9 M and predicted possible binding modes in catalytic site for these active compounds. The thiazole nitrogen in compound 6   h formed a strong hydrogen bonding interaction with side chain Gln635 having distance 2.01 Å and rest part of this inhibitor is present close to Val640. The most potent derivative 6   h have highest binding affinity with binding energy −6.178 kcal/mol. It is concluded based upon our results that 6   a and 6   h are most promising compounds from this series and provide a basis for rationale design of most potent urease inhibitors.