CAJ | 학술논문

目的：应用肝微粒体模型研究以灯盏乙素及其苷元为先导的系列化合物代谢特征,筛选代谢性质优于灯盏乙素的化合物。方法采用UPLC-MS/MS法测定大鼠肝微粒体温孵体系中不同时间点各候选化合物的含量,筛选T1/2和CLint较优的候选化合物,比较候选化合物与灯盏乙素的酶促动力学特征及其转化情况。结果与灯盏乙素及其苷元相比,候选化合物W11的半衰期较长、清除率较低；W11酶促动力学参数Vmax为(10.25依0.93)μmol·min-1·g-1,Km 为(4.48依0.10)μmol·L-1,CLint为(2.29依0.23) L·min-1·g-1；灯盏乙素酶促动力学参数 Vmax为(45.95依9.50)μmol · min-1·g-1,Km 为(10.19依1.66)μmol·L-1,CLint为(4.48依0.20) L·min-1·g-1；W11可能代谢为M1(W11脱掉甲基后分子质量为577的化合物),并释放出灯盏乙素。结论候选化合物W11可能具有优于灯盏乙素的代谢性质并能释放活性代谢产物灯盏乙素。
목적：응용간미립체모형연구이등잔을소급기감원위선도적계렬화합물대사특정,사선대사성질우우등잔을소적화합물。방법채용UPLC-MS/MS법측정대서간미립체온부체계중불동시간점각후선화합물적함량,사선T1/2화CLint교우적후선화합물,비교후선화합물여등잔을소적매촉동역학특정급기전화정황。결과여등잔을소급기감원상비,후선화합물W11적반쇠기교장、청제솔교저；W11매촉동역학삼수Vmax위(10.25의0.93)μmol·min-1·g-1,Km 위(4.48의0.10)μmol·L-1,CLint위(2.29의0.23) L·min-1·g-1；등잔을소매촉동역학삼수 Vmax위(45.95의9.50)μmol · min-1·g-1,Km 위(10.19의1.66)μmol·L-1,CLint위(4.48의0.20) L·min-1·g-1；W11가능대사위M1(W11탈도갑기후분자질량위577적화합물),병석방출등잔을소。결론후선화합물W11가능구유우우등잔을소적대사성질병능석방활성대사산물등잔을소。
Aim To study the pharmacokinetic char-acteristics of serial compounds that took the scutellarin and scutellarein as lead compounds by using the model of in vitro liver microsomes, and to screen compounds whose medicinal properties were superior to scutellarin and scutellarein. Methods The content of candidate compounds at different times by incubation system of rat liver microsome was determined using UPLC-MS/MS method. Candidate compounds that contained opti-mum T1/2 and CLint were screened. Enzyme kinetics and conversions of candidate compounds were com-pared with those of scutellarin and scutellarein. Re-sults The T1/2 and CLint were optimum of W11 com-pared with those of scutellarin and scutellarein; the Vmax, Km and CLint of compound W11 were (10.25 ±2.59 ) μmol · min-1 · g-1 , ( 4.64 ±0.24 ) μmol · L-1 and ( 2.29 ±0.23 ) L · min-1 · g-1; the Vmax , Km and CLint of scutellarin were (45.95±9.50) μmol · min-1 · g-1 , ( 10.19 ± 1.66 ) μmol · L-1 and (4.48±0.20) L·min-1 ·g-1; W11 might be me-tabolized into scutellarin and M1 ( a compound with mo-lecular weight of 577 after demethylating ) . Conclu-sion The pharmacokinetic properties of candidate compound W11 are better than those of scutellarin, and it could release scutellarin.