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

Abstract

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.

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

“…We also reported previously that KI for non-nucleosides inhibitors increases by size and shape. 20 Fig. 4a shows the correlation between predicted by equation (3) and experimental values of log KI.…”

“…QSAR studies show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constant. 20 We have investigated effect of salts; solvents; and ionic surfactants on the structure and activity of adenosine deaminase (ADA) by UV-Vis spectrophotometery, circular dichroism and molecular dynamics (MD). 21 Relative activity, experimental and computational helix content, total accessible surface area (ASA) and exposed charged surface area were obtained.…”

“…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.…”

Effects of surfactant, salt and solvent on the structure and activity of adenosine deaminase: Molecular dynamic and spectrophotometric studies

“…Kinetic, thermodynamic, molecular dynamic and QSAR studies on the interaction of inhibitors with ADA were investigated [16][17][18][19][20][21]. Understanding the interaction of ADA with solvent, salt and surfactant is then critical for the development of the next generation of pharmaceutical agents and structural studies.…”

Effect of Cationic and Anionic Porphyrins on the Structure and Activity of Adenosine Deaminase

“…Enzyme inhibition has been studied by different methods and techniques. 30,31 The effect of some denaturants on the ADA structure and activity has also been studied. 32 The interaction of pigment with human serum albumin has been investigated by fluorescence, UV-vis spectrophotometry and calorimetery.…”