title: In Vitro Metabolism of Artepillin C by Rat and Human Liver Microsomes.
abstract: Artepillin C, a natural product present in the Brazilian green propolis, has several biological properties. Among these properties, the antitumor action of this product is noteworthy and makes it a promising drug candidate for the treatment of several types of cancer. This paper describes thein vitrometabolism of Artepillin C in rat and human liver microsomes. The rat model suggested a sigmoidal profile for the metabolism, adapted to the Hill's kinetic model. The enzymatic kinetic parameters were as follows: maximal velocity = 0.757 ± 0.021 µmol/mg protein/min, Hill coefficient = 10.90 ± 2.80, and substrate concentration at which half-maximal velocity of a Hill enzyme is achieved = 33.35 ± 0.55 µM. Based on these results, the calculatedin vitrointrinsic clearance for Artepillin C was 16.63 ± 1.52 µL/min/mg protein. Thein vitrometabolism assay conducted on the human model did not fit any enzymatic kinetic model. Two novel metabolites were formed in both mammal microsomal models and their chemical structures were elucidated for the first time. The main human cytochrome P450 isoforms involved in Artepillin C metabolism had been identified, and the results suggest a majority contribution of CYP2E1 and CYP2C9 in the formation of the two metabolites.
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Daniel Blascke
authors.initials: DB
authors.lastname: Carrão
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Nayara Cristina Perez
authors.initials: NCP
authors.lastname: de Albuquerque
authors.affiliation: Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lucas Maciel Mauriz
authors.initials: LMM
authors.lastname: Marques
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Antônio Eduardo Miller
authors.initials: AEM
authors.lastname: Crotti
authors.affiliation: Nucleus of Bioassays, Biosynthesis and Ecophysiology of Natural Products - NuBBE, Sao Paulo State University - UNESP - Chemistry Institute, Department of Organic Chemistry, Araraquara, Sao Paulo, Brazil.
authors.forename: Alan Cesar
authors.initials: AC
authors.lastname: Pilon
authors.affiliation: Nucleus of Bioassays, Biosynthesis and Ecophysiology of Natural Products - NuBBE, Sao Paulo State University - UNESP - Chemistry Institute, Department of Organic Chemistry, Araraquara, Sao Paulo, Brazil.
authors.forename: Vanderlan Da Silva
authors.initials: VDS
authors.lastname: Bolzani
authors.affiliation: Apis Flora Industrial e Comercial Ltda, Ribeirão Preto, SP, Brazil.
authors.forename: Andresa Aparecida
authors.initials: AA
authors.lastname: Berretta
authors.affiliation: Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Anderson Rodrigo Moraes
authors.initials: ARM
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D010666:Phenylpropionates / Q000378:metabolism*; D011429:Propolis / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D010666:Phenylpropionates; C102259:artepillin C; D011429:Propolis; D065729:Cytochrome P-450 CYP2C9; D019392:Cytochrome P-450 CYP2E1