Authors:
Gonring-Salarini, Karla L. 1 ; Conti, Raphael 2 ; de Andrade, Jean Paulo 1 ; Borges, Barbara Juliana P. 1 ; Aguiar, Anna Caroline C. 3 ; de Souza, Juliana O. 3 ; Zanini, Camila L. 3 ; Oliva, Glaucius 3 ; Tenorio, Juan Carlos 4 ; Ellena, Javier 4 ; Bastida, Jaume 5 ; Guido, Rafael V. C. 3 ; Borges, Warley de S. 1, 2
Abstract:
A combined phytochemical, crystallographic and biological study of Worsleya procera roots was performed. Fifteen alkaloids were identified by gas chromatography mass spectrometry (GC-MS) and seven of them were isolated. The structures of the alkaloids were elucidated by spectroscopic methods, and a detailed crystallographic study of tazettine was carried out. The isolated alkaloids and the obtained extracts were tested in vitro against Plasmodium falciparum (3D7 and K1 strains) and human hepatocarcinoma cells (HepG2) to assess their antiplasmodial and cytotoxic effects, respectively. One of the isolated alkaloid derivatives, lycorine, exhibited antiplasmodial activity against both sensitive (3D7) and resistant (K1) parasite strains in the low micromolar range (half-maximal sample inhibitory concentration (IC50) values of 2.5 and 3.1 µM, respectively) and displayed a low cytotoxicity profile, with a selectivity index greater than 100. Our findings indicate that lycorine is a hit for antimalarial drug discovery.
1 Departamento de Ciências Farmacêuticas, Universidade Federal do Espírito Santo (UFES), Av. Marechal Campos, 1468, 29043-900 Vitória-ES, Brazil
2 Departamento de Química, Universidade Federal do Espírito Santo (UFES), Av. Fernando Ferrari, 514, 29075-910 Vitória- ES, Brazil
3 Instituto de Física de São Carlos, Universidade de São Paulo (USP), Av. João Dagnone, 1100, 13563-120 São Carlos-SP, Brazil
4 Laboratório Multiusuário de Cristalografia Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo (USP), Av. Trabalhador São Carlense, 400, CP 369, 13560-570 São Carlos-SP, Brazil
5 Department de Biologia, Sanitat i Medi Ambient, Facultat de Farmàcia, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain
Link to article: http://jbcs.sbq.org.br/imagebank/pdf/2018-0657AR.pdf27
