Inhibition of xanthine oxidase by benzothiazinone analogues.
Fourteen synthetic benzothiazinone analogues were tested for their inhibitory effects on xanthine oxidase. The enzyme, xanthine oxidase (XO) catalyses the oxidation of hypoxanthine to xanthine and of xanthine to uric acid, which has a lambda max of 295 nm, forming the basis for a spectrophotometric assay for the activity of xanthine oxidase. The results showed that 2-amino-4H-1,3-benzothiazine-4-one (1), 2-guanidino-4H-1,3-benzothiazin-4-one (2) and rhodanine (3) display inhibitory effects on xanthine oxidase with an order of activity of IC50 = 5.54, 5.60 and 121.40 microM respectively. The apparent inhibition constants (Ki) were 5.12, 19.47 and 206.23 microM, and induced non-competitive, mixed type (non-competitive-uncompetitive) and mixed type (non-competitive-uncompetitive) inhibitions respectively with respect to the substrate xanthine.
Sheu
S Y
SY
School of Pharmacy, Taipei Medical College, Taiwan, ROC.
Lin
C Y
CY
Wu
J D
JD
Chiang
H C
HC
D004791:Enzyme Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D013844:Thiazoles; D014969:Xanthine Oxidase