Skálová L, Nobilis M, Szotáková B, Wsól V, Kvasnicková E
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
Drug Metabol Drug Interact. 1998;14(4):221-33. doi: 10.1515/dmdi.1998.14.4.221.
Benfluron N-oxide [5-(2-N-oxo-2-N,N'-dimethylaminoethoxy)-7-oxo-7-H-benzo[c]fluorene] is a biologically active substance which displays a cytostatic effect on several experimental tumour cells. The main metabolic pathway of benfluron N-oxide in vitro and in vitro--its reduction to the parent tertiary amine benfluron--and the role of cytochrome P450 in this reduction were studied. The value of the benfluron N-oxide/benfluron redox potential as a criterion of suitability of the substrate for cytochrome P450 reductase activity was determined. Results of induction and inhibition studies on rats suggest that cytochromes P4502B and P4502E1 participate in microsomal reduction of benfluron N-oxide. Unlike most cytochrome P450 catalysed reactions, the reduction of benfluron N-oxide also occurs under aerobic conditions. Microsomes induced by phenobarbital, ethanol or beta-naphthoflavone showed no significantly greater inhibitory effect of oxygen on benfluron N-oxide reduction.
苯氟隆氮氧化物[5-(2-N-氧代-2-N,N'-二甲基氨基乙氧基)-7-氧代-7-H-苯并[c]芴]是一种对多种实验肿瘤细胞具有细胞抑制作用的生物活性物质。研究了苯氟隆氮氧化物在体内外的主要代谢途径——其还原为母体叔胺苯氟隆，以及细胞色素P450在该还原过程中的作用。测定了苯氟隆氮氧化物/苯氟隆氧化还原电位的值，作为底物对细胞色素P450还原酶活性适用性的标准。对大鼠的诱导和抑制研究结果表明，细胞色素P4502B和P4502E1参与了苯氟隆氮氧化物的微粒体还原。与大多数细胞色素P450催化的反应不同，苯氟隆氮氧化物的还原在有氧条件下也会发生。由苯巴比妥、乙醇或β-萘黄酮诱导的微粒体对氧对苯氟隆氮氧化物还原的抑制作用没有显著增强。
