| Autor: |
Khan M; Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman.; Department of Biochemistry, University of Malakand, Totakan, Pakistan., Nizamani A; Muhammad Medical College, Ibn-e-Sina University, Mirpurkhas, Sindh, Pakistan., Shah L; Department of Biochemistry, Hazara University Mansehra, Mansehra,Pakistan., Ullah I; Department of Biochemistry, Hazara University Mansehra, Mansehra,Pakistan., Waqas M; Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman., Halim SA; Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman., Ataya FS; Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia., Elgazzar AM; Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.; Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan., Batiha GE; Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt., Khan A; Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman., Al-Harrasi A; Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman. |
| Abstrakt: |
The hyperactivity of urease enzymes plays a crucial role in the development of hepatic coma, hepatic encephalopathy, urolithiasis, gastric and peptic ulcers. Additionally, these enzymes adversely impact the soil's nitrogen efficiency for crop production. In the current study 100 known drugs were tested against Jack Bean urease and Proteus mirabilis urease and identified three inhibitors i.e. terbutaline (compound 1 ), Ketoprofen (compound 2 ) and norepinephrine bitartrate (compound 3 ). As a result, these compounds showed excellent inhibition against Jack Bean urease i.e. (IC 50 = 2.1-11.3 µM), and Proteus mirabilis urease (4.8-11.9 µM). Moreover, in silico studies demonstrate maximum interactions of compounds in the enzyme's active site. Furthermore, intermolecular interactions between compounds and enzyme atoms were examined using STD-NMR spectrophotometry. In parallel, molecular dynamics simulation was carried out to study compounds dynamic behavior within the urease binding region. Urease remained stable during most of the simulation time and ligands were bound in the protein active pocket as observed from the Root mean square deviation (RMSD) and ligand RMSD analyses. Furthermore, these compounds display interactions with the crucial residues, including His492 and Asp633, in 100 ns simulations. In the binding energy analysis, norepinephrine bitartrate exhibited the highest binding energy (-76.32 kcal/mol) followed by Ketoprofen (-65.56 kcal/mol) and terbutaline (-62.15 kcal/mol), as compared to acetohydroxamic acid (-52.86 kcal/mol). The current findings highlight the potential of drug repurposing as an effective approach for identifying novel anti-urease compounds.Communicated by Ramaswamy H. Sarma. |
