title: 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 = 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.
authors.affiliation: Faculty of Chemistry, Damghan University of Basic Science, Damghan, Iran. ajloo@dubs.ac.ir
authors.forename: Davood
authors.initials: D
authors.lastname: Ajloo
authors.forename: Ali A
authors.initials: AA
authors.lastname: Saboury
authors.forename: Niloofar
authors.initials: N
authors.lastname: Haghi-Asli
authors.forename: Ghasem
authors.initials: G
authors.lastname: Ataei-Jafarai
authors.forename: Ali A
authors.initials: AA
authors.lastname: Moosavi-Movahedi
authors.forename: Mosayeb
authors.initials: M
authors.lastname: Ahmadi
authors.forename: Karim
authors.initials: K
authors.lastname: Mahnam
authors.forename: Saeed
authors.initials: S
authors.lastname: Namaki
mesh_terms: 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
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D009711:Nucleotides; D004008:Diclofenac; D000243:Adenosine Deaminase; D001241:Aspirin