In vitro metabolism study and enzymatic inhibition of natural product piplartine employing human liver microsomes and supersomes.

• Grant number: 13/04188-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2013
• Effective date (End): February 23, 2017
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Fernanda de Lima Moreira
• Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). 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

Historically, a portion of marketed drugs originated from natural products and/or their derivatives. Due to the pharmacological potential of these molecules, an important step in the initial development of a new drug is the assessment of their behavior in the cytochrome P450 (CYP 450), including studies of drug interactions. In this context, the natural product piplartine has been highlighted. This is an alkaloid found in plants of the genus Piper and several studies have shown promising pharmacological properties, among which stands out the antitumor activity. However, for this substance with proven biological activity, it is necessary to perform pre-clinical studies on their metabolic profile in the face of cytochrome P450 enzymes and drug interaction studies. Therefore, this project aims to conduct a study of in vitro metabolism with this molecule by determining the enzymatic kinetic parameters and to characterize the possible metabolites that may be formed. In addition, studies will be undertaken through the drug interaction studies of enzymatic inhibition by using human hepatic microsomes. In addition the CYP isoform responsible for its metabolism will be determinate by using human supersomes.

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)

MOREIRA, FERNANDA DE LIMA; MOREIRA, MARCELA DE LIMA; PILON, ALAN CESAR; LOPES, NORBERTO PEPORINE. Leishmanicidal Effects of Piperlongumine (Piplartine) and Its Putative Metabolites. Planta Medica, v. 84, n. 15, p. 1141-1148, OCT 2018. Web of Science Citations: 2.

MOREIRA, FERNANDA L.; MARQUES, LUCAS M. M.; LOPES, NORBERTO P.; DE OLIVEIRA, ANDERSON R. M. In vitro metabolism studies of natural products are crucial in the early development of medicines. PHYTOCHEMISTRY REVIEWS, v. 16, n. 2, p. 355-373, APR 2017. Web of Science Citations: 2.