Abstract:
: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.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Messiano GB,Santos RA,Ferreira Lde S,Simões RA,Jabor VA,Kato MJ,Lopes NP,Pupo MT,de Oliveira ARdoi
10.1016/j.jpba.2012.08.028subject
Has Abstractpub_date
2013-01-01 00:00:00pages
240-4eissn
0731-7085issn
1873-264Xpii
S0731-7085(12)00487-6journal_volume
72pub_type
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