scholarly journals Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Muhammad Rashid ◽  
Hummera Rafique ◽  
Sadia Roshan ◽  
Shazia Shamas ◽  
Zafar Iqbal ◽  
...  
Keyword(s):  
Docking Studies ◽  
Binding Energies ◽  
Urease Inhibitor ◽  
Jack Bean Urease ◽  
Substituted Anilines ◽  
Jack Bean ◽  
Chemical Structures ◽  
Mixed Ester ◽  
Urease Enzyme ◽  
Better Than

A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a–f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC50 1.6 ± 0.2  nM, better than the standard thiourea having IC50 472.1 ± 135.1  nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver–Burk plots (kinetics study) indicated about 4b derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of −7.8 and −7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea.

4-Aminocoumarin based Aroylthioureas as Potential Jack Bean Urease Inhibitors; Synthesis, Enzyme Inhibitory Kinetics and Docking Studies

2020 ◽  
Vol 16 (2) ◽  
pp. 229-243 ◽  
Author(s):  
Tanzeela A. Fattah ◽  
Aamer Saeed ◽  
Zaman Ashraf ◽  
Qamar Abbas ◽  
Pervaiz A. Channar ◽  
...  
Keyword(s):  
Radical Scavenging ◽  
Docking Studies ◽  
Target Protein ◽  
Dynamics Simulation ◽  
Stable Complex ◽  
Urease Inhibitors ◽  
Jack Bean Urease ◽  
Thiourea Derivatives ◽  
Jack Bean ◽  
Urease Enzyme

Background: Urease enzyme catalyzes the hydrolysis of urea into ammonia and CO2, excess ammonia causes global warming and crop reduction. Ureases are also responsible for certain human diseases such as stomach cancer, peptic ulceration, pyelonephritis, and kidney stones. New urease inhibitors are developed to get rid of such problems. Objective: This article describes the synthesis of a series of novel 1-aroyl-3-(2-oxo-2H-chromen-4- yl)thiourea derivatives (5a-j) as Jack bean urease inhibitors. Methods: Freshly prepared aryl isothiocyanates were reacted with 4-aminocoumarin in the same pot in an anhydrous medium of acetone. The structures of the title thioureas (5a-j) were ascertained by their spectroscopic data. The inhibitory effects against jack bean urease were determined. Results: It was found that compounds 5i and 5j showed excellent activity with IC50 values 0.0065 and 0.0293, µM respectively. Compound 5i bearing 4-methyl substituted phenyl ring plays a vital role in enzyme inhibitory activity. The kinetic mechanism analyzed by Lineweavere-Burk plots revealed that compound 5i inhibits the enzyme non-competitively. The Michaelis-Menten constant Km and inhibition constants Ki calculated from Lineweavere-Burk plots for compound 5i are 4.155mM and 0.00032µM, respectively. The antioxidant activity results displayed that compound 5j showed excellent radical scavenging activity. The cytotoxic effects determined against brine shrimp assay showed that all of the synthesized compounds are non-toxic to shrimp larvae. Molecular docking studies were performed against target protein (PDBID 4H9M) and it was determined that most of the synthesized compounds exhibited good binding affinity with the target protein. Molecular dynamics simulation (MDS) results revealed that compound 5i forms a stable complex with target protein showing little fluctuation. Conclusion: Based upon our investigations, it is proposed that 5i derivative may serve as a lead structure for devising more potent urease inhibitors.

Mechanism, kinetics, and antimicrobial activities of 2-hydroxy-1-naphthaldehyde semicarbazone as a new Jack bean urease inhibitor

2016 ◽  
Vol 40 (4) ◽  
pp. 3520-3527 ◽  
Author(s):  
Xue-Yue Jiang ◽  
Liang-Quan Sheng ◽  
Chong-Fu Song ◽  
Na-Na Du ◽  
Hua-Jie Xu ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
Antimicrobial Activities ◽  
Urease Inhibitor ◽  
Jack Bean Urease ◽  
Inhibitory Mechanism ◽  
Jack Bean ◽  
Fluorescence Titration ◽  
Titration Assay

A new inhibitor of jack bean urease, 2-hydroxy-1-naphthaldehyde semicarbazone, was synthesized and employed to investigate the inhibitory mechanism of HNDSC on jack bean urease by kinetic and fluorescence titration assay, and its antibacterial activities were also investigated.

Synthesis, biological evaluation and docking studies of some novel isatin-3-hydrazonothiazolines

RSC Advances ◽  
2016 ◽  
Vol 6 (65) ◽  
pp. 60826-60844 ◽  
Author(s):  
Maqbool Ahmad ◽  
Humayun Pervez ◽  
Sumera Zaib ◽  
Muhammad Yaqub ◽  
Muhammad Moazzam Naseer ◽  
...  
Keyword(s):  
Active Site ◽  
Binding Mode ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Jack Bean Urease ◽  
Jack Bean

The putative binding mode of compound 6i in the active site of Jack bean urease.

Jack Bean Urease Inhibitors, and Antioxidant Activity Based on Palmitic acid Derived 1-acyl-3- Arylthioureas: Synthesis, Kinetic Mechanism and Molecular Docking Studies

Drug Research ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 596-605 ◽  
Author(s):  
Aamer Saeed ◽  
Sajid ur-Rehman ◽  
Pervaiz Channar ◽  
Fayaz Larik ◽  
Qamar Abbas ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Docking Study ◽  
Kinetic Mechanism ◽  
Inhibition Mechanism ◽  
Initial Structure ◽  
Urease Inhibitors ◽  
Jack Bean Urease ◽  
Jack Bean ◽  
Ic50 Value ◽  
Urease Enzyme

AbstractA series of acylthioureas was synthesized and their inhibitory effects on the DPPH and jack bean urease were evaluated. The results showed that all of the synthesized compounds exhibited significant jack bean urease inhibitory activities. Especially, 1-(4-chlorophenyl)-3 palmitoylthiourea 5a bearing 4-chloro substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with an IC50 value 0.0170 μM compared to the IC50 value of 4.720 μM of thiourea used as standard. The inhibition mechanism analyzed by Lineweaver–Burk plots revealed that the type of inhibition of compound 5a on tyrosinase was noncompetitive. The docking study against jack bean urease enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e showed the highest binding affinity with the active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that all compounds and particularly 5a may serve as a structural template for the design and development of novel urease inhibitors Graphical Abstract.

Flavonoids as Natural Inhibitors of Jack Bean Urease Enzyme

2016 ◽  
Vol 13 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Jalaluddin A. J. Awllia ◽  
Maryam AL-Ghamdi ◽  
Etimad Huwait ◽  
Sumaira Javaid ◽  
. Atia-tul-Wahab ◽  
...  
Keyword(s):  
Jack Bean Urease ◽  
Jack Bean ◽  
Urease Enzyme ◽  
Natural Inhibitors

Synthesis, crystal structure, molecular docking studies and bio-evaluation of some N4-benzyl-substituted isatin- 3-thiosemicarbazones as urease and glycation inhibitors

2018 ◽  
Vol 24 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Humayun Pervez ◽  
Nazia Khan ◽  
Jamshed Iqbal ◽  
Sumera Zaib ◽  
Muhammad Yaqub ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Docking ◽  
Brine Shrimp ◽  
Inhibitory Concentration ◽  
Lethal Dose ◽  
Artemia Salina ◽  
Docking Studies ◽  
Urease Enzyme ◽  
Inhibitory Potential ◽  
Better Than

Abstract Fifteen N4-benzyl-substituted isatin-3-thiosemicarbazones 5a–o were synthesized and evaluated for their urease and glycation inhibitory potential. Lemna aequinocitalis growth and Artemia salina assays were also done to determine their phytotoxic and toxic effects. All compounds are potent inhibitors of the urease enzyme, displaying inhibition [half maximal inhibitory concentration (IC50)=1.08±0.12–11.23±0.19 μm] superior to that of the reference inhibitor thiourea (IC50=22.3±1.12 μm). Compounds 5c, 5d, 5h, 5j,k are potent antiglycating agents, showing glycation inhibitory activity better than that of the reference inhibitor rutin (IC50 values 209.87±0.37–231.70±6.71 vs. 294.5±1.5 μm). In the phytotoxicity assay, 11 thiosemicarbazones 5a–d, 5g, 5h, 5j–l, 5n,o are active, demonstrating 5–100% growth inhibition of L. aequinocitalis at the highest tested concentrations (1000 or 500 μg/mL). In the brine shrimp (A. salina) lethality bioassay, three derivatives 5b, 5j and 5o are active with median lethal dose (LD50) values of 3.63×10−5, 2.90×10−5 and 2.31×10−4 m, respectively.

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