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Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Coumarinylthiazolyl Iminothiazolidinone Hybrids as Potent Urease Inhibitors
Author(s) -
Mahmood ShamsUl,
Nazir Yasir,
Saeed Aamer,
Abbas Qamar,
Ashraf Zaman
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202000429
Subject(s) - thiourea , chemistry , thiazole , stereochemistry , hydrogen bond , urease , sodium methoxide , active site , docking (animal) , enzyme , combinatorial chemistry , methanol , molecule , organic chemistry , medicine , nursing
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.