QSAR Analysis for ADA upon Interaction with a Series of Adenine Derivatives as Inhibitors

Moosavi‐Movahedi, A. A.; Safarian, Shahrokh; Hakimelahi, G. H.; Ataei, G.H.; Ajloo, Davood; Panjehpour, S.; Riahi, Siavash; Mousavi, Mir F.; Mardanyan, Sona; Soltani, Naghmeh; Khalafi-Nezhad, Ali; Sharghi, Hashem; Moghadamnia, H.; Saboury, Ali Akbar

doi:10.1081/ncn-120030719

Cited by 29 publications

(20 citation statements)

References 20 publications

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“…The majority of them describe the size, thus we refer to them as the size factor. In previous work [34] we also showed that volume decreases the logK I while here we obtained several descriptors which show a size property. Factor 2 includes L/BW, RGYR, SPH, ASP and FDI which belong to geometrical and HOMA and AROM which belong to aromaticity indices [39].…”

Section: Isothermal Titration Calorimetry (Itc)supporting

confidence: 71%

“…Fortunately, in the literature, [24 -33] there are several inhibitors, where their kinetic parameters were reported during their interaction with ADA under environmental conditions that are similar those of our studies. In the previous work we reported only the QSAR of nucleoside inhibitors [34]. However, in the present study, we considered QSAR and factor analysis on nucleoside (Scheme 1a, compounds 1 -11) and non-nucleoside inhibitors (Scheme 1b compounds 12 -20).…”

Section: Isothermal Titration Calorimetry (Itc)mentioning

confidence: 99%

“…The kinetic parameters of adenosine deaminase such as K m and K I were determined in the absence and presence of adenine derivatives as well as the QSAR of these derivatives was studied. QSAR analysis revealed that the binding affinity of the adenine nucleoside upon interaction with ADA depends on the molecular volume, dipole moment of the molecule, electric charge, and the highest positive charge for the related molecules [34].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac

Ajloo

Saboury

Haghi-Asli

et al. 2007

Journal of Enzyme Inhibition and Medicinal Chemistry

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The kinetic and thermodynamic effects of aspirin and diclofenac on the activity of adenosine deaminase (ADA) were studied in 50 mM phosphate buffer pH ¼ 7.5 at 27 and 378C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 378C and the inhibition constants are 42.8 and 96.8 mM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 278C and uncompetitive at 378C with inhibition constants of 56.4 and 30.0 mM, at respectively. The binding constant and enthalpy of binding, at 278C are 45 mM, 2 64.5 kJ/mol and 61 mM, 2 34.5 kJ/mol for aspirin and diclofenac. Thermodynamic data revealed that the binding process for these ADA inhibitors is enthalpy driven. QSAR studies by principal component analysis implemented in SPSS show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constants.

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Section: Isothermal Titration Calorimetry (Itc)supporting

confidence: 71%

Section: Isothermal Titration Calorimetry (Itc)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac

Ajloo

Saboury

Haghi-Asli

et al. 2007

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Kinetic parameters were used for the QSAR analysis and as such, we found some theoretical descriptors which correlated the binding affinity of ADA towards several adenine nucleosides as inhibitors. 19 The kinetic parameters for adenosine deaminase were determined as well as the QSAR of these derivatives was studied. QSAR analysis revealed that the binding affinity depends on the molecular volume, dipole moment, electric charge, and the highest positive charge.…”

Section: Introductionmentioning

confidence: 99%

“…QSAR analysis revealed that the binding affinity depends on the molecular volume, dipole moment, electric charge, and the highest positive charge. 19 We previously investigated the effect of aspirin and diclofenac as non-steroid anti-inflammatory drugs (NSAIDs) 20 on ADA using spectrophotometry and isothermal titration calorimetry. QSAR studies show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constant.…”

Section: Introductionmentioning

confidence: 99%

Effects of Dimaine, Diacid and Dintitro Derivatives on the Inhibition of Adenosine Deaminase; Experimental, Molecular Docking and QSAR Studies

2009

Bulletin of the Korean Chemical Society

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Effects of some diacid, diamine and dinitro aromatic compounds on the structure and activity of adenosine deaminase (ADA) were investigated by UV-Vis spectrophotometry in 50 mM phosphate buffer at pH = 7.5 and 27 o C and molecular docking studies. The results showed that all tested ligands are showing inhibition; five ligands are uncompetitive and other two ligands are mixed of competitive and noncompetetive inhibitors with majority of competitive behavior. For the later case analysis was done based on competitive inhibition. Diacids have larger size and higher inhibition constant (KI) relative to others. A logical correlation between calculated free energy of binding and experimental values was obtained for un-competitive. Experimental and calculated data showed that competitive inhibitors are distributed near the active site of enzyme and form several cluster of ranks, whereas uncompetitive inhibitors bind to the enzyme-substrate complex and distributed far from the active site. Results of structure-activity relationship showed that, larger, more hydrophobe, less spherical and more aromatic ligands have higher inhibition constants.

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A novel QSPR study of normalized migration time for drugs in capillary electrophoresis by new descriptors: Quantum chemical investigation

2008

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Some drugs' migration time (MT) has been studied employing quantitative structure-property relationship using new descriptors that are able to predict MT value with high accuracy. MT property modeling of the drugs was established as a function of the new theoretically derived descriptors applying multiple linear regressions and partial least-squares regression. The genetic algorithm was used to select those variables that resulted in the best-fitted models. To select a set of descriptors that are most relevant to MT, illustrating the affecting degree for the affinity of different descriptors, the linear models with 1-14 variables were constructed and were then investigated based on F-value, squared regression coefficients of cross-validated (Q2), adjusted R2 (R2adj) and standard error of estimate (S) statistical parameters. Finally, the best model with ten variables was selected. Statistical parameters of the test set, such as standard deviation error in test, were 0.559 and 0.616, while relative error of test was equal to 7.648 and 8.497% for multiple linear regressions and partial least-squares models, respectively, confirming the good predictive ability of the model. Since the capillary lengths were not the same for the drugs in the data set, MT values were normalized based on a specific capillary before modeling, which is also one of the advantages of this method, enabling us to use the model for different capillary lengths.

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QSAR Analysis for ADA upon Interaction with a Series of Adenine Derivatives as Inhibitors

Cited by 29 publications

References 20 publications

Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac

Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac

Effects of Dimaine, Diacid and Dintitro Derivatives on the Inhibition of Adenosine Deaminase; Experimental, Molecular Docking and QSAR Studies

A novel QSPR study of normalized migration time for drugs in capillary electrophoresis by new descriptors: Quantum chemical investigation

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