Dihydropyrimidones: A ligands urease recognition study and mechanistic insight through in vitro and in silico approach
| Autor: | Sahib Gul Afridi, Farman Ali Khan, Khalid Mohammed Khan, Shahnaz Perveen, Shahbaz Shamim, Kanwal, Ajmal Khan, Farman Ali, Muhammad Arif Lodhi, Nisar Ullah |
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| Rok vydání: | 2020 |
| Předmět: |
biology
Urease 010405 organic chemistry Chemistry Stereochemistry In silico Organic Chemistry Active site 01 natural sciences In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Docking (molecular) biology.protein Urea Bioorganic chemistry General Pharmacology Toxicology and Pharmaceutics Cytotoxicity |
| Zdroj: | Medicinal Chemistry Research. 30:120-132 |
| ISSN: | 1554-8120 1054-2523 |
| Popis: | Scaffold varied dihydropyrimidone derivatives 1–20 were evaluated for their selective urease inhibitory kinetics potential. Compounds 1, 2, 3, 4, 5, 6, and 12 were found to be the most promising urease inhibitors and showed the inhibition (Ki values) within the range of 9.9 ± 0.5 to 18.3 ± 0.4 µM. Lineweaver–Burk plot, Dixon plot and their secondary replots confirm that all these molecules have followed competitive mode of inhibition. Docking arrangements (MOE) revealed that all the ligands bind in the active site and therefore compete with substrate urea. Molecular docking studies of all compounds have confirmed the binding interactions of various ligands with the amino acid residues as well as Ni atoms of active site. Furthermore, these compounds 1–20 were also tested for their cytotoxicity against human neutrophils and plants and were found to be non-toxic. |
| Databáze: | OpenAIRE |
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