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.

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.

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.

Contribution of Resveratrol in the Development of Novel Urease Inhibitors: Synthesis, Biological Evaluation and Molecular Docking Studies

2019 ◽  
Vol 22 (4) ◽  
pp. 245-255 ◽  
Author(s):  
Ritu Kataria ◽  
Anurag Khatkar
Keyword(s):  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Vilsmeier Reaction ◽  
Parent Molecule ◽  
Ic50 Value ◽  
Urease Enzyme ◽  
Protein Pocket

Aims and Objective: A new library of resveratrol derivatives was designed and synthesized in excellent yield via two-step reaction utilizing Vilsmeier reaction as the first step and subsequent addition of substituted aromatic amine in the second step. Methods: Synthesized compounds were investigated for their antioxidant as well as for in vitro inhibition activity against jack bean urease enzyme. Compounds R3b and R4 with IC50 value 18.85±0.15 and 21.60±0.19µM against urease enzyme and 6.01±0.07 and 7.52±0.14µM in vitro- DPPH free radical scavenging activity have emerged as most active molecules from the selected library. Molecular simulation studies were also carried out for determining the interaction detail of newly synthesized compounds within a protein pocket. Results and Conclusion: Newly synthesized compounds were found to possess better docking score (-5.941 to -6.894) and binding energy (-46.854 to -56.455) as compared to the parent resveratrol (-5.45 and -20.155) which revealed that the newly synthesized compounds bind in a better way as compared to the parent molecule

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.

scholarly journals Evaluation of binding and inhibition mechanism of dietary phytochemicals with sphingosine kinase 1: Towards targeted anticancer therapy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Preeti Gupta ◽  
Taj Mohammad ◽  
Rashmi Dahiya ◽  
Sonam Roy ◽  
Omar Mohammed Ali Noman ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Inflammatory Diseases ◽  
Sphingosine Kinase ◽  
Competitive Inhibitor ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Inhibition Mechanism ◽  
Stable Complex ◽  
Sphingosine Kinase 1 ◽  
Dietary Phytochemicals

AbstractSphingosine kinase 1 (SphK1) has recently gained attention as a potential drug target for its association with cancer and other inflammatory diseases. Here, we have investigated the binding affinity of dietary phytochemicals viz., ursolic acid, capsaicin, DL-α tocopherol acetate, quercetin, vanillin, citral, limonin and simvastatin with the SphK1. Docking studies revealed that all these compounds bind to the SphK1 with varying affinities. Fluorescence binding and isothermal titration calorimetric measurements suggested that quercetin and capsaicin bind to SphK1 with an excellent affinity, and significantly inhibits its activity with an admirable IC50 values. The binding mechanism of quercetin was assessed by docking and molecular dynamics simulation studies for 100 ns in detail. We found that quercetin acts as a lipid substrate competitive inhibitor, and it interacts with important residues of active-site pocket through hydrogen bonds and other non-covalent interactions. Quercetin forms a stable complex with SphK1 without inducing any significant conformational changes in the protein structure. In conclusion, we infer that quercetin and capsaicin provide a chemical scaffold to develop potent and selective inhibitors of SphK1 after required modifications for the clinical management of cancer.

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
Sign in / Sign up

Export Citation Format

Share Document