In vitro metabolism studies of the antitumor Clerodane diterpene casearin X

• Grant number: 12/03446-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2012
• Effective date (End): January 31, 2016
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Cristiane Masetto de Gaitani
• Grantee: Rodrigo Moreira da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 09/51812-0 - Development of a platform for the study of in vitro and in vivo metabolism of natural products, a need for pre-clinical testing system, AP.BTA.TEM

Abstract

The main pharmacological properties of Casearia sylvestris, a species of tree which leaves are used in folk medicine were previously established. The potent cytotoxic activity of casearin X, major clerodane diterpene isolated from the leaves of C. sylvestris, was recently demonstred agains human tumor cells. In Brazil, which holds the largest biodiversity on the planet, the development of new drugs from natural sources has been recognized as an important strategy for health policies. Taking into account that the advance in research of new drug candidates requires an in vitro and in vivo pre-clinical evaluation of safety and efficacy, the aim of this work is to study the in vitro metabolism of the casearin X, using hepatic microsomal fractions from rats and humans. To ensure the reliability of the results, an analytical method for the quantification of the casearin X and subsequent estimation of Michaelis-Mentem (Km) constant, maximum velocity (Vmax) and intrinsic clearance (CL) will be developed and validated. If it is observed the presence of metabolites, they will be identified using mass spectrometry and/or nuclear magnetic resonance. The results of this project will provide essential information for development of a possible new drug, and contributes to the thematic project which is linked. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, RODRIGO MOREIRA; DE GAITANI, CRISTIANE MASETTO; MAURIZ MARQUES, LUCAS MACIEL; BARACO, KARINA FRAIGE; CAVALHEIRO, ALBERTO JOSE; BERALDO DE MORAES, LUIZ ALBERTO; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Characterization of Casearin X Metabolism by Rat and Human Liver Microsomes. Planta Medica, v. 85, n. 4, p. 282-291, MAR 2019. (16/06366-5, 16/07597-0, 12/03446-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Rodrigo Moreira da. In vitro characterization of metabolism and intestinal absorption of casearin X. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.