Green synthesis, inhibition studies of yeast α-glucosidase and molecular docking of pyrazolylpyridazine amines

Chaudhry, Faryal; Ather, Abdul Qayuum; Akhtar, M. Humayoun; Shaukat, Ayesha; Ashraf, Mohammad; al‐Rashida, Mariya; Munawar, Munawar Ali; Khan, Misbahul Ain

doi:10.1016/j.bioorg.2017.02.003

Cited by 17 publications

(7 citation statements)

References 30 publications

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“…The mol files of the ligands (urease inhibitors) were created using ACD ChemSketch. For docking studies, standard steps of ligand and receptor preparation were followed using BioSolve IT's LeadIT software …”

Section: Resultsmentioning

confidence: 99%

“…For docking studies, standard steps of ligand and receptor preparation were followed using BioSolve IT's LeadIT software. [27][28][29]34,35] The urease active site contains two Ni 2 + ions, 13 histidine residues, between residues 479 and 607, are present in the bimetallic active site. CYS595, which is crucial for enzymatic catalysis, is also located in this region.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

“…This highlights the perpetual need of new improved inhibitors which could deal effectively with bacterial infections. Our research group has continuously been exploring biological potentials of different azolic compounds . As a continuation, herein, we discover an efficient series of urease inhibitors which could address the current desire of better anti‐urease drugs.…”

Section: Introductionmentioning

confidence: 97%

“…Our research group has continuously been exploring biological potentials of different azolic compounds. [26][27][28][29][30] As a continuation, herein, we discover an efficient series of urease inhibitors which could address the current desire of better anti-urease drugs. To the best of our knowledge, such trisubstituted imidazoles have not been tested for antiurease activity so far.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

et al. 2020

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Towards discovery of effective urease inhibitors; we disclose here a hybrid series of imidazole and pyrazole motifs as potent antiurease agents. A para-toluenesulfonic acid (TsOH) catalyzed, facile synthetic approach was employed for the preparation of targeted molecular designs in good yields upto 94 %. The novel scaffolds were characterized by different spectroscopic means (FTIR, NMR, and Mass spectrometry) and elemental analysis helped to identify the purity of these compounds. Afterwards, the derivatives was tested against Jack bean's urease enzyme to explore their inhibiting potencies. All analogues (4 a-4 l) were found active against the studied enzyme in comparison with the standard drug thiourea (IC 50 = 21.26 � 0.12 μM). However, following dibromo substituted derivatives: 4 f, 4 g, 4 h, 4 i, 4 j, 4 k, and 4 l were surfaced out as potent urease inhibitors among the series. The identified lead candidates were meta-nitro substituted 4 k with IC 50 = 0.7 � 0.002 μM and a para-nitro containing compound 4 l with IC 50 = 1.0 � 0.003 μM. As observed in docking calculations, ionic and hydrogen bonding, π-stacking, interaction with nickel ions and other hydrophobic interactions probably stabilized the ligand bindings at the active site of urease.

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Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

et al. 2020

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“…The cut-off distance for Van der Waal's interactions (calculated using the particle mesh Ewald method [44]) was 10 Å. Hydrogen covalent bonds were constrained using SHAKE [45]. This length of simulation is consistent with recent studies on engineered proteins (for example, [46][47][48][49]).…”

Section: Molecular Dynamicsmentioning

confidence: 67%

Modulation of the mobility of a key region in human galactokinase: Impacts on catalysis and stability

McAuley

Huang

Timson

2018

Bioorganic Chemistry

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Galactokinase catalyses the phosphorylation of α-d-galactose and some structurally related monosaccharides. The enzyme is of interest due to its potential as a biocatalyst for the production of sugar 1-phosphates and due to its involvement in the inherited metabolic disease type II galactosemia. It has been previously shown that a region (residues 231-245) in human galactokinase often has altered mobility when active site residues are varied. We hypothesised that the reverse may be true and that designing changes to this region might affect the functioning of the active site of the enzyme. Focussing on four residues (Leu-231, Gln-242, Glu-244 and Glu-245) we conducted molecular dynamics simulations to explore the effects of changing these residues to glycine or serine. In most cases the variations resulted in local changes to the 231-245 region and global changes to the root mean squared fluctuation (RMSF) of the protein. The four serine variants were expressed as recombinant proteins. All had altered steady state enzyme kinetic parameters with α-d-galactose as a substrate. However, these changes were generally less than ten-fold in magnitude. Changes were also observed with 2-deoxy-α-d-galactose, α-d-galactosamine and α-d-talose as substrates, including (in some cases) loss of detectable activity, suggesting that these variations can tune the specificity of the enzyme. This study demonstrates that activity and specificity of human galactokinase can be modulated by variations designed to affect active site flexibility. It is likely that this principle can be generalised to other enzymes.

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Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Firdaus

Siddiqui

Alam

et al. 2023

Archiv der Pharmazie

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The α-glucosidase is a validated target to develop drugs for treating type 2 diabetes mellitus. The existing α-glucosidase inhibitors have certain shortcomings related to side effects and route of synthesis. Accordingly, it is inevitable to develop new chemical templates as α-glucosidase inhibitors. Pyrazole derivatives have a special place in medicinal chemistry because of various biological activities. Recently, pyrazole-based heterocyclic compounds have emerged as a promising scaffold to develop α-glucosidase inhibitors. This study focuses on the recently reported pyrazole-based α-glucosidase inhibitors, including their biological activity (in vivo, in vitro, and in silico), structure-activity relationship, and ways of synthesis. The literature revealed the development of several promising pyrazole-based α-glucosidase inhibitors and new synthetic routes for their preparation. The encouraging α-glucosidase inhibitory results of the pyrazole-based heterocyclic compounds make them an attractive target for further research. The authors also foresee the arrival of the pyrazole-based α-glucosidase inhibitors in clinical practice.

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Green synthesis, inhibition studies of yeast α-glucosidase and molecular docking of pyrazolylpyridazine amines

Cited by 17 publications

References 30 publications

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

Modulation of the mobility of a key region in human galactokinase: Impacts on catalysis and stability

Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

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