Wsól V, Szotáková B, Kvasnicková E, Fell A F
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
J Chromatogr A. 1998 Feb 27;797(1-2):197-201. doi: 10.1016/s0021-9673(97)01166-7.
One of the main metabolites of oracin (I) ¿6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno[1,2- c] isoquinoline¿, a potential cytostatic drug, is 11-dihydrooracin (II) ¿(+),(-)-6-[2-(2-hydroxyethyl)aminoethyl]-5-oxo-11-hydroxy-5,6-dihydro-1 1H- indeno[1,2-c]isoquinoline¿, a metabolite formed by the reduction of oracin's pro-chiral centre on C 11. This metabolite has been found in all laboratory species in vitro and in vivo and it constitutes the main metabolite in man. The stereospecificity of reducing enzymes participating in the oracin biotransformation pathway was investigated using microsomal preparations from standard laboratory animals. Enzyme stereospecificity has been defined as preferential formation by the enzyme of the (+) or (-) stereoisomer of II. Significant interspecies differences were observed in the stereospecificity of the respective biotransformation enzymes. HPLC quantitative determinations of both enantiomers were performed using a Chiralcel OD-R column as chiral stationary phase with excellent resolution and stability.
奥拉辛（I）[6-[2-(2-羟乙基)氨基乙基]-5,11-二氧代-5,6-二氢-11H-茚并[1,2-c]异喹啉]是一种潜在的细胞生长抑制剂，其主要代谢产物之一是11-二氢奥拉辛（II）[(+),(-)-6-[2-(2-羟乙基)氨基乙基]-5-氧代-11-羟基-5,6-二氢-11H-茚并[1,2-c]异喹啉]，它是由奥拉辛C11上的前手性中心还原形成的代谢产物。这种代谢产物在所有实验室物种的体外和体内均有发现，并且是人体中的主要代谢产物。使用标准实验动物的微粒体制剂研究了参与奥拉辛生物转化途径的还原酶的立体特异性。酶的立体特异性定义为酶优先形成II的(+)或(-)立体异构体。在各自生物转化酶的立体特异性方面观察到了显著的种间差异。使用Chiralcel OD-R柱作为手性固定相，对两种对映体进行了HPLC定量测定，具有出色的分离度和稳定性。
