Kinetic,thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac |
| |
Authors: | Davood Ajloo Ali A Saboury Niloofar Haghi-Asli Ghasem Ataei-Jafarai Ali A Moosavi-Movahedi Mosayeb Ahmadi |
| |
Institution: | 1. Faculty of Chemistry, Damghan University of Basic Science, Damghan, Iran;2. Institute of Biochemistry and Biophysics, The University of Tehran, Tehran, Iran;3. Faculty of Paramedical Science, Shahid Beheshti University of Medical Science, Tehran, Iran;4. Faculty of Mathematical Science, Damghan University of Basic Science, Damghan, Iran |
| |
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 = 7.5 at 27 and 37°C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 37°C and the inhibition constants are 42.8 and 96.8 μM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 27°C and uncompetitive at 37°C with inhibition constants of 56.4 and 30.0 μM, at respectively. The binding constant and enthalpy of binding, at 27°C are 45 μM, ? 64.5 kJ/mol and 61 μM, ? 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. |
| |
Keywords: | Adenosine deaminase inhibitors quantitative structure-activity relationship QSAR aspirin diclofenac principal component analysis |
|
|