Fong K L, Hwang B Y
Drug Metab Dispos. 1984 Jan-Feb;12(1):14-9.
The in vitro aromatization of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (DCTQ) has been studied. Incubation of DCTQ with various rat liver subcellular fractions in the presence and absence of cofactors suggested that oxidative reactions catalyzed by microsomal enzymes were involved in this aromatization pathway. In addition to the aromatization product, 7,8-dichloroisoquinoline, three other metabolites were detected in the 9000g supernatant and microsomal incubations. By comparing the chromatographic and spectral data of the metabolites with those obtained for synthetic compounds, these three metabolites were identified as the hydroxylamine, nitrone, and the partially oxidized product (3,4-dihydro) of DCTQ. When added to microsomes, the hydroxylamine and the 3,4-dihydro derivatives were also metabolized to the 7,8-dichloroisoquinoline, and the conversions were NADPH and oxygen dependent. These findings, together with kinetic data, suggested that the aromatization of DCTQ catalyzed by rat liver microsomes was a stepwise oxidative reaction, with N-hydroxylation of DCTQ as the initial step.
对7,8-二氯-1,2,3,4-四氢异喹啉（DCTQ）的体外芳构化反应进行了研究。在有和没有辅因子的情况下，将DCTQ与各种大鼠肝脏亚细胞组分一起孵育，结果表明微粒体酶催化的氧化反应参与了该芳构化途径。除了芳构化产物7,8-二氯异喹啉外，在9000g上清液和微粒体孵育物中还检测到了其他三种代谢产物。通过将这些代谢产物的色谱和光谱数据与合成化合物的相关数据进行比较，确定这三种代谢产物分别为DCTQ的羟胺、硝酮和部分氧化产物（3,4-二氢）。当添加到微粒体中时，羟胺和3,4-二氢衍生物也会代谢为7,8-二氯异喹啉，且这些转化依赖于NADPH和氧气。这些发现与动力学数据一起表明，大鼠肝脏微粒体催化的DCTQ芳构化反应是一个逐步氧化反应，以DCTQ的N-羟基化为起始步骤。
