Planta Med 2012; 78 - PH11
DOI: 10.1055/s-0032-1320670

In vitro metabolism study of the bioactive lignan (-)-Grandisin

GB Messiano 1, RA da S Santos 2, LS Ferreira 1, RA Simões 1, MJ Kato 3, NP Lopes 1, MT Pupo 1, ARM Oliveira 2
  • 1Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040–903, Ribeirão Preto, SP, Brazil
  • 2Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040–901, Ribeirão Preto, SP, Brazil
  • 3Instituto de Química, Universidade de São Paulo, 05513–970, São Paulo, SP, Brazil

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 Vmax and Km were 1.46±0.034µmol/mg protein/h and 8.99±0.488µM, respectively. In addition, the formation of dihydro-grandisin, characterized by GC-MS, by mammalian systems indicated the involvement of a CYP450 enzyme type.