In vitro metabolism of copalic and kaurenoic acids in rat and human liver microsomes

Author(s)

Mauro, Mariana ^[1] ; da Silva, Rodrigo Moreira ^[2] ; de Campos, Michel Leandro ^[3] ; Bauermeister, Anelize ^[2] ; Lopes, Norberto Peporine ^[2] ; de Moraes, Natalia Valadares ^[1]

Affiliation

^[1] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Farmacos & Medicamentos, BR-14800903 Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Mato Grosso, Inst Ciencias Saude, BR-78550000 Sinop, MT - Brazil

• Document type: Journal article
• Source: Química Nova; v. 44, n. 6, p. 700-708, 2021.
• Web of Science Citations: 0

Abstract

Copalic (CA) and kaurenoic (KA) acids are the main diterpenes found in the oleoresin extracted from the copaiba tree (Copaifera sp). This study aimed to characterize the metabolism of CA and KA in rat and human liver microsomes using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The in vitro assays showed deviations from the Michaelian kinetics in the metabolism of CA and KA. Putative metabolites of CA and KA were characterized by LC-MS/MS using electrospray ionization (ESI) with time of flight (LC-ESI-TOF) and ion-trap (LC-ESI-IT) systems and identified as a CA isomer and 16,17-dihydroxy-kaurenoic acid, respectively. CA and KA are subject to extensive metabolism with each passage through the liver with extraction ratios (E) estimated as 0.97 and 0.99, respectively. In conclusion, the kinetic parameters and metabolites described here might support drug development and the traditional use. (AU)

• FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants