title: In Vitro Inhibition Of Three Different Drugs Used In Rheumatoid Arthritis Treatment On Human Serum Paraoxanase 1 Enzyme Activity.
abstract: We studied in vitro effects of three different drugs (ibuprofen, meloxicam and methotrexate) which are often used in rheumatoid arthritis (RA) treatment on human serum paraoxanase1 (PON1) enzyme activity. The drugs used in RA treatment decreased the in vitro PON1 activity. The inhibition mechanism of ibuprofen and methotrexate were noncompetitive whereas meloxicam was a competitive inhibitor. The IC50 values for ibuprofen, meloxicam and methotrexate were calculated to be 0.35 mM, 0.10 mM, and 0.18 mM, respectively, and the Ki constants were calculated to be 0.890 mM, 0.125 mM, and 0.260 mM, respectively. The IC50 and Ki values showed the maximum inhibition of meloxicam drugs. We propose a prediction scheme for the interaction of meloxicam with the PON1 active site because we thought that meloxicam interacts with the amino acids which are in the PON1 enzyme active site. The results we found showed that these drugs which are often used in RA treatment in vitro inhibit the activity of the enzyme with different inhibition mechanisms at low doses.
authors.affiliation: Department of Biochemistry, Division of Pharmaceutical Basic Sciences, Faculty of Pharmacy, Erzincan University, 24030, Erzincan-Turkey. edilek@erzincan.edu.tr.
authors.forename: Esra
authors.initials: E
authors.lastname: Dilek
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Polat
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification*; D020134:Catalytic Domain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D000077239:Meloxicam; D008727:Methotrexate / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D018501:Antirheumatic Agents; D013843:Thiazines; D013844:Thiazoles; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D000077239:Meloxicam; D007052:Ibuprofen; D008727:Methotrexate