Determination of accurate KI values for tight-binding enzyme inhibitors: an in silico study of experimental error and assay design

2004 ◽  
Vol 327 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Dennis J. Murphy
Keyword(s):  
In Silico ◽  
Experimental Error ◽  
Enzyme Inhibitors ◽  
Tight Binding ◽  
In Silico Study ◽  
Assay Design

Kinetic determination of tight-binding impurities in enzyme inhibitors

2003 ◽  
Vol 319 (2) ◽  
pp. 272-279 ◽  
Author(s):  
Petr Kuzmic ◽  
Craig Hill ◽  
Matthew P Kirtley ◽  
James W Janc
Keyword(s):  
Enzyme Inhibitors ◽  
Tight Binding ◽  
Kinetic Determination

High-Throughput Screening of Enzyme Inhibitors: Automatic Determination of Tight-Binding Inhibition Constants

2000 ◽  
Vol 281 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Petr Kuzmič ◽  
Steve Sideris ◽  
Lynne M. Cregar ◽  
Kyle C. Elrod ◽  
Kenneth D. Rice ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Enzyme Inhibitors ◽  
Tight Binding ◽  
Automatic Determination ◽  
Binding Inhibition ◽  
Inhibition Constants

scholarly journals A rapid RP-HPLC method for the simultaneous estimation of Ivacaftor and Tezacaftor and in silico study of their metabolitic products

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Madhuri Donakonda ◽  
Srija Indrakanti ◽  
Praveen Kumar Pasala ◽  
Malleswari Desari ◽  
Shireesha Kammari
Keyword(s):  
Human Plasma ◽  
In Silico ◽  
Dosage Form ◽  
Hplc Method ◽  
Simultaneous Estimation ◽  
Discovery Studio ◽  
Rp Hplc ◽  
Validation Parameters ◽  
In Silico Study

Abstract Background This study was designed to develop a reliable method for estimation of Ivacaftor and Tezacaftor in pure and its pharmaceutical dosage form by RP-HPLC in human plasma. Molecular docking studies were carried out and the results were visualized using PyMol and Discovery studio visualizer (Discovery studio visualizer ver. 2.5). The pharmacokinetic properties such as Swiss ADME and pKCSM of the Ivacaftor and its metabolites Ivacaftor M1, M6 and Tezacaftor and metabolites Tezacaftor M1, M2 were predicted. In admetSAR, web-based query tools incorporating a molecular built-in interface enable the database to be queried by SMILES. Results A simple, linear, precise, and accurate RP-HPLC method was developed and validated for the determination of Ivacaftor (IVA) and Tezacaftor (TEZ) in human plasma. Chromatographic separation was achieved isocratically on Inspire C18, (4.6 × 250 mm, 5 μm) column at 30 °C. Mobile phase consisting of methanol and 0.05% formic acid in ratio of 95:5 with flow rate of 1 mL/min with injection volume 20 μl detector used is PDA at 235 nm. The developed method was validated according to ICH guidelines and found to be linearity range was found to be for TEZ (10–50 μg/mL) and IVA (15–75 μg/mL). IVA and TEZ drugs and its metabolites were retrieved from the PubChem database and the 2D chemical structures were generated from SMILES notation by using the Chemsketch Software. The structure was viewed using Swiss-PDB Viewer to form a better understanding of the molecule for toxicity and biological activity prediction. Conclusion The results obtained by the proposed method from validation parameters and from assay confirmed that the determination of Tezacaftor (TEZ) and Ivacaftor (IVA) in their combined dosage form in human plasma was sensitive and selective method. In silico study has revealed that IVA and its metabolites IVA M1, IVA M6 are according to Lipinski rule. The oral bioactivity of IVA was found to be more when compared to its metabolites (Molinspiration) and TEZ and its metabolites TEZ M1, TEZ M2 even though they have the molecular weight > 500, but all other parameters from Molinspiration revealed better oral bioactivity of TEZ M2. Validation of the developed isocratic RP-HPLC procedure revealed that, regardless of how the sample was purified, the method was characterized by good linearity, sensitivity, reproducibility, specificity, and low values of LOD (0.090 μg/mL) and LOQ (0.275 μg/mL). From the in silico docking results, it is quite evident that metabolites of TEZ and IVA have the great potential against cystic fibrosis.

Stoichiometric Determination of Graphite Intercalation Compounds Using Rutherford Backscatiering Spectrometry

1983 ◽  
Vol 27 ◽  
Author(s):  
L. Salamanca-Riba ◽  
B.S. Elman ◽  
M.S. Dresselhaus ◽  
T. Venkatesan
Keyword(s):  
Experimental Error ◽  
Rutherford Backscattering Spectrometry ◽  
Rutherford Backscattering ◽  
Intercalation Compounds ◽  
Graphite Intercalation Compounds ◽  
X Ray ◽  
Donor And Acceptor ◽  
Graphite Intercalation ◽  
Non Destructive

ABSTRACTRutherford backscattering spectrometry (RBS) is used to characterize the stoichiometry of graphite intercalation compounds (GIC). Specific application is made to several stages of different donor and acceptor compounds and to commensurate and incommensurate intercalants. A deviation from the theoretical stoichiometry is measured for most of the compounds using this non-destructive method. Within experimental error, the RBS results agree with those obtained from analysis of the (00ℓ) x-ray diffractograms and weight uptake measurements on the same samples.

In Silico Study of Structural and Geometrical Requirements of Natural Sesquiterpene Lactones with Trypanocidal Activity

2013 ◽  
Vol 13 (10) ◽  
pp. 1407-1414 ◽  
Author(s):  
L. Fabian ◽  
V. Sulsen ◽  
F. Frank ◽  
S. Cazorla ◽  
E. Malchiodi ◽  
...  
Keyword(s):  
In Silico ◽  
Sesquiterpene Lactones ◽  
Trypanocidal Activity ◽  
In Silico Study

In Silico Study of 1, 4 Alpha Glucan Branching Enzyme and Substrate Docking Studies

2020 ◽  
Vol 17 (1) ◽  
pp. 40-50
Author(s):  
Farzane Kargar ◽  
Amir Savardashtaki ◽  
Mojtaba Mortazavi ◽  
Masoud Torkzadeh Mahani ◽  
Ali Mohammad Amani ◽  
...  
Keyword(s):  
Phylogenetic Tree ◽  
In Silico ◽  
Alpha Helix ◽  
In Silico Analysis ◽  
Glycogen Storage ◽  
Docking Studies ◽  
Random Coil ◽  
Special Topic ◽  
Industrial Biotechnology ◽  
In Silico Study

Background: The 1,4-alpha-glucan branching protein (GlgB) plays an important role in the glycogen biosynthesis and the deficiency in this enzyme has resulted in Glycogen storage disease and accumulation of an amylopectin-like polysaccharide. Consequently, this enzyme was considered a special topic in clinical and biotechnological research. One of the newly introduced GlgB belongs to the Neisseria sp. HMSC071A01 (Ref.Seq. WP_049335546). For in silico analysis, the 3D molecular modeling of this enzyme was conducted in the I-TASSER web server. Methods: For a better evaluation, the important characteristics of this enzyme such as functional properties, metabolic pathway and activity were investigated in the TargetP software. Additionally, the phylogenetic tree and secondary structure of this enzyme were studied by Mafft and Prabi software, respectively. Finally, the binding site properties (the maltoheptaose as substrate) were studied using the AutoDock Vina. Results: By drawing the phylogenetic tree, the closest species were the taxonomic group of Betaproteobacteria. The results showed that the structure of this enzyme had 34.45% of the alpha helix and 45.45% of the random coil. Our analysis predicted that this enzyme has a potential signal peptide in the protein sequence. Conclusion: By these analyses, a new understanding was developed related to the sequence and structure of this enzyme. Our findings can further be used in some fields of clinical and industrial biotechnology.

Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Mahboob Ali ◽  
Momin Khan ◽  
Khair Zaman ◽  
Abdul Wadood ◽  
Maryam Iqbal ◽  
...  
Keyword(s):  
In Silico ◽  
Enzyme Inhibitors ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Type Ii Diabetes Mellitus ◽  
Spectroscopic Techniques ◽  
Chalcone Derivatives ◽  
In Silico Studies ◽  
Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

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