Developing a scaffold for urease inhibition based on benzothiazoles: Synthesis, docking analysis, and therapeutic potential
| Autor: | Özge Tuzcuoğlu, Mustafa Emirik, Nimet Baltaş, Musa Özil |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
In silico
Pharmaceutical Science Thio Molecular Dynamics Simulation Hydroxamic Acids Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Benzothiazoles Enzyme Inhibitors chemistry.chemical_classification biology Acetohydroxamic acid Active site Oxime Urease Combinatorial chemistry Molecular Docking Simulation Enzyme Benzothiazole chemistry Docking (molecular) biology.protein medicine.drug |
| Zdroj: | Archiv der Pharmazie. 354:2100200 |
| ISSN: | 1521-4184 0365-6233 |
| DOI: | 10.1002/ardp.202100200 |
| Popis: | The synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzothiazole derivatives are reported. The title compounds in the two series, namely, 2-({5-[(benzothiazol-2-ylthio)methyl]-1,3,4-oxadiazol-2-yl}thio)-1-(4-substituted-phenyl)ethan-1-one and 2-(benzothiazol-2-ylthio)-1-(4-substituted-phenyl)ethan-1-one oxime, were synthesized by the reaction of benzo[d]thiazole-2-thiol with different kinds of intermediates in several steps using both conventional and microwave techniques. All compounds were found to have an excellent degree of urease-inhibitory potential ranging between 16.16 ± 0.54 and 105.32 ± 2.10 µM when compared with the standard inhibitor acetohydroxamic acid with IC50 = 320.70 ± 4.24 µM. The structure-activity relationship was established in detail. The binding interactions of the compounds with the enzyme were confirmed through molecular docking. Further, 100 -ns molecular dynamics simulations were performed to investigate the stability and structural perturbations experienced by the most potent compound over the urease active site. |
| Databáze: | OpenAIRE |
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