Xanthine oxidase (XO): relative configuration of complexes formed by the enzyme, 2- or 8-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines. XII.
Several 2- or 8-n-alkyl-hypoxanthines and a 2,8-di-n-pentyl-hypoxanthine were synthesized and tested as substrates or inhibitors of Xanthine Oxidase (XO). 8-Alkyl derivatives showed a substrate behaviour, whereas 2-alkyl substituted compounds were non-substrates and inhibitors. 2,8-di-n-pentyl-hypoxanthine was ineffective as inhibitor. The comparison between their activity allowed us to conclude that the complexes formed by the enzyme and the cited n-alkylhypoxanthines or 2-n-alkyl-8-azahypoxanthines involve their N(3) and N(9) positions in all the cases. The position of the n-alkyl chain determines the disposition of the molecule inside the complex: 2-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines gave complexes with the same orientation of heterocyclic moieties, opposite that given by 8-n-alkyl-hypoxanthines.
Biagi
G
G
Istituto di Chimica Farmaceutica e Tossicologica, Facoltà di Farmacia, Pisa.
Giorgi
I
I
Livi
O
O
Scartoni
V
V
Tonetti
I
I
Lucacchini
A
A
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007042:Hypoxanthines / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008892:Milk / Q000201:enzymology; D008968:Molecular Conformation; D010944:Plants / Q000201:enzymology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D007042:Hypoxanthines; D014969:Xanthine Oxidase