Biagi G, Giorgi I, Livi O, Scartoni V, Tonetti I, Lucacchini A
Istituto di Chimica Farmaceutica e Tossicologica, Facoltà di Farmacia, Pisa.
Farmaco. 1993 Mar;48(3):357-74.
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.
合成了几种2-或8-正烷基次黄嘌呤以及一种2,8-二正戊基次黄嘌呤，并将其作为黄嘌呤氧化酶（XO）的底物或抑制剂进行测试。8-烷基衍生物表现出底物行为，而2-烷基取代的化合物则不是底物且是抑制剂。2,8-二正戊基次黄嘌呤作为抑制剂无效。对它们活性的比较使我们得出结论，在所有情况下，酶与所述正烷基次黄嘌呤或2-正烷基-8-氮杂次黄嘌呤形成的复合物涉及其N(3)和N(9)位置。正烷基链的位置决定了分子在复合物中的排列方式：2-正烷基次黄嘌呤和2-正烷基-8-氮杂次黄嘌呤形成的复合物中杂环部分的取向相同，与8-正烷基次黄嘌呤形成的复合物相反。
