Evaluation of the cytotoxicity of the alkaloid govaniadine in human cell lines

• Grant number: 15/02592-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 11, 2016
• End date: August 10, 2016
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Norberto Peporine Lopes
• Grantee: Lucas Maciel Mauriz Marques
• Supervisor: Hans-Ulrich Humpf
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Munster, Germany
• Associated to the scholarship: 13/16496-5 - In vitro, in vivo metabolism and pharmacokinetic profile evaluation of the alkaloid govaniadine, BP.DR

Abstract

The protoberberines are distributed in such plant families as Papaveraceae, Berberidaceae, Fumariaceae, Menispermaceae, Ranunculaceae, Rutaceae, Annonaceae and exhibit multiple pharmacological activities, such as antibacterial and antitumor. The ability of cytotoxic protoberberine alkaloids to act as topoisomerase I or II poisonings was reported to be related to the antitumor activity. Plant extracts, pure compounds and alkaloids from different species of the genus Corydalis (family Fumariaceae) showed an inhibitory effect against hepatitis virus, tumors, liver cancer, as well as acesodyne and sedative. Tetrahydroprotoberberine-type alkaloids, especially govaniadine isolated from Corydalis are identified as a new category of dopamine receptor ligands, anti-malarial and antileishmanicidal agents. The results from the grant# 2013/16496-5 have shown that govaniadine is metabolised by the CYP450 enzymatical system and in the next step we would like to measure the effects on cells, e.g. cytotoxicity including apoptosis, necrosis. There are several of well established in vitro models to perform cytotoxicity studies: human skin fibroblasts, Hep3B, Cell Counting Kit-8 (CCK-8) and Hek cells. The studies using cell culture models have several advantages such as the possibility of monitoring the process by the use of controlled conditions and the reduction of the use of animals. Although several tetrahydroprotoberberine-type alkaloids have been reported, but no bioactivity of pure compounds of it's has been reported yet and data concerning govaniadine is still lacking. Furthermore such knowledge will be essential to support our previous results. (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)

MARQUES, LUCAS M. M.; BEHRENS, MATTHIAS; KALININA, SVETLANA; ROTTKORD, ULRIKE; ADHIKARI, ACHYUT; SHRESTHA, RAM L. S.; HUMPF, HANS-ULRICH; LOPES, NORBERTO P.. Govaniadine Evaluation of Cytotoxicity and Permeability in Cell Culture. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 30, n. 3, MAY 2020. (15/02592-8, 13/16496-5)