Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903, Ribeirão Preto, São Paulo, Brazil.
J Pharm Biomed Anal. 2013 Jan;72:240-4. doi: 10.1016/j.jpba.2012.08.028. Epub 2012 Aug 31.
The lignan (-)-grandisin has shown important pharmacological activities, such as citotoxicity and antiangiogenic, antibacterial and trypanocidal activities. So, it has been considered as a potential drug candidate. In the early drug development process, drug metabolism is one of the main parameters that should be evaluated; therefore, the biotransformation of this lignan by rat liver microsomes was investigated for the first time. In order to perform the biotransformation study and to determine the kinetic parameters, a simple, sensitive and selective HPLC method was developed and fully validated. After method validation, the biotransformation study was accomplished and the kinetic parameters were determined. The biotransformation study obeyed the Michaelis-Menten kinetics. The V(max) and K(m) were 1.46 ± 0.034 μmol/mg protein/h and 8.99 ± 0.488 μM, respectively. In addition, the formation of dihydro-grandisin, characterized by GC-MS, by mammalian systems indicated the involvement of a CYP450 enzyme type.
（-）-松脂素具有细胞毒性、抗血管生成、抗菌和杀锥虫等重要的药理活性，因此被认为是一种有潜力的候选药物。在早期药物开发过程中，药物代谢是需要评估的主要参数之一；因此，首次研究了大鼠肝微粒体对这种木脂素的生物转化。为了进行生物转化研究并确定动力学参数，开发了一种简单、灵敏和选择性的 HPLC 方法，并对其进行了充分验证。方法验证后，完成了生物转化研究并确定了动力学参数。生物转化研究符合米氏动力学。Vmax 和 Km 分别为 1.46±0.034 μmol/mg 蛋白/h 和 8.99±0.488 μM。此外，通过 GC-MS 分析哺乳动物系统中形成的二氢松脂素表明涉及 CYP450 酶型。
