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.

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.

Iminothiazoline-Sulfonamide Hybrids as Jack Bean Urease Inhibitors; Synthesis, Kinetic Mechanism and Computational Molecular Modeling

2015 ◽  
Vol 87 (3) ◽  
pp. 434-443 ◽  
Author(s):  
Aamer Saeed ◽  
Shams-ul Mahmood ◽  
Muhammad Rafiq ◽  
Zaman Ashraf ◽  
Farukh Jabeen ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Kinetic Mechanism ◽  
Urease Inhibitors ◽  
Jack Bean Urease ◽  
Jack Bean ◽  
Computational Molecular Modeling

Molecular Docking of Natural Phenolic Compounds for the Screening of Urease Inhibitors

2019 ◽  
Vol 20 (5) ◽  
pp. 410-421 ◽  
Author(s):  
Ritu Kataria ◽  
Anurag Khatkar
Keyword(s):  
Phenolic Compounds ◽  
In Silico ◽  
Docking Study ◽  
Peptic Ulcers ◽  
Jack Bean Urease ◽  
Jack Bean ◽  
Lead Compounds ◽  
Modelling Techniques ◽  
Natural Phenolic Compounds

Background:Bacterial ureases have been the cause of various human and animal pathogenicity including hepatic encephalopathy, hepatic coma urolithiasis, gastric and peptic ulcers, pyelonephritis, and urinary catheter encrustation by the production of ammonia. Hence, in view of the side effects of existing drugs, there is a strong need to discover, more safe, effective and potent compounds for the treatment of infections caused by urease.Methods:For this purpose, several natural phenolic compounds have been screened by molecular modelling techniques, wherein the phenolic compounds were docked to the active site of Jack bean urease (PDB ID 3LA4) using the Schrodinger docking software.Results:The lead compounds were identified via in-silico screening technique where docking score, binding energy, ADME and toxicity data were considered to screen the lead compounds as compared with the available standard drugs. From the docking study of screened natural phenolic compounds, five compounds diosmin, morin, chlorogenic acid, capsaicin and resveratrol were selected based upon their better affinity towards the receptor and were considered for further wet lab studies.Conclusion:The in-silico results were confirmed by in vitro experiments by use of the Jack bean urease using Weatherburn method.

scholarly journals Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking

Molecules ◽  
2017 ◽  
Vol 22 (8) ◽  
pp. 1352 ◽  
Author(s):  
Pervaiz Channar ◽  
Aamer Saeed ◽  
Fernando Albericio ◽  
Fayaz Larik ◽  
Qamar Abbas ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kinetic Mechanism ◽  
Jack Bean Urease ◽  
Jack Bean

scholarly journals Synthesis, Crystal Structures and Urease Inhibition of 4-Bromo-N’-(1-(pyridin-2-yl)ethylidene)benzohydrazide and Its Dinuclear Copper(II) Complex

2021 ◽  
Vol 68 (4) ◽  
pp. 804-810
Author(s):  
Hui Zhao ◽  
Xiu-Rui Liu ◽  
Xue Wang ◽  
Jing Hu ◽  
Ya-Jun Cai ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Elemental Analysis ◽  
Spectroscopic Studies ◽  
Urease Inhibition ◽  
Jack Bean Urease ◽  
Jack Bean ◽  
Dinuclear Copper ◽  
Single Crystal Structures ◽  
Ic50 Value ◽  
Bridging Groups

A new dinuclear copper(II) complex [Cu2(μ-Br)2L2] · 0.5 MeOH with the benzohydrazone ligand 4-bromo-N’-(1-(pyridin-2-yl)ethylidene)benzohydrazide (HL) has been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic studies. Single crystal structures of the complex and the benzohydrazone compound were studied. The Cu atoms in the complex are coordinated by two benzohydrazone ligands and two Br bridging groups, forming square pyramidal coordination. The complex has good inhibitory activity on Jack bean urease, with IC50 value of 1.38 μmol L-1.

scholarly journals Plectrabarbene, a New Abietane Diterpene from Plectranthus barbatus Aerial Parts

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2365
Author(s):  
Nawal M. Al Musayeib ◽  
Musarat Amina ◽  
Gadah Abdulaziz Al-Hamoud ◽  
Gamal A. Mohamed ◽  
Sabrin R.M. Ibrahim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Active Site ◽  
Docking Study ◽  
Inhibition Mechanism ◽  
Ache Inhibition ◽  
Molecular Docking Study ◽  
Spectral Techniques ◽  
Aerial Parts ◽  
Insight Into

A new abietane diterpene namely plectrabarbene (2), together with two known compounds: sugiol (1) and 11,14-dihydroxy-8,11,13-abietatrien-7-one (3) have been isolated from the aerial parts of Plectranthus barbatus Andr. (Labiatae). The structures of these compounds were determined by various spectral techniques (e.g., UV, IR, NMR, and FAB) and by comparison with the literature data. A molecular docking study of the isolated diterpenes (1–3) was performed with AChE to gain an insight into their AChE inhibition mechanism. The results of docking experiments revealed that the all tested compounds showed binding affinity at the active site of AchE in comparison to donepezil.

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