Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac.
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 degrees C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 37 degrees C and the inhibition constants are 42.8 and 96.8 microM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 27 degrees C and uncompetitive at 37 degrees C with inhibition constants of 56.4 and 30.0 microM, at respectively. The binding constant and enthalpy of binding, at 27 degrees C are 45 microM, - 64.5 kJ/mol and 61 microM, - 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.
Ajloo
Davood
D
Faculty of Chemistry, Damghan University of Basic Science, Damghan, Iran. ajloo@dubs.ac.ir
Saboury
Ali A
AA
Haghi-Asli
Niloofar
N
Ataei-Jafarai
Ghasem
G
Moosavi-Movahedi
Ali A
AA
Ahmadi
Mosayeb
M
Mahnam
Karim
K
Namaki
Saeed
S
D000243:Adenosine Deaminase / Q000737:chemistry*; D058892:Adenosine Deaminase Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D004008:Diclofenac / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D015233:Models, Statistical; D009711:Nucleotides / Q000737:chemistry; D025341:Principal Component Analysis; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013696:Temperature; D013816:Thermodynamics
D058892:Adenosine Deaminase Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D009711:Nucleotides; D004008:Diclofenac; D000243:Adenosine Deaminase; D001241:Aspirin