In vitro Antiplasmodial Activity and Cytotoxicity of Vincadifformine and Its Semisynthetic Derivatives

Abstract

An indole alkaloid with aspidospemane structure possessing a potential antiplasmodial activity,vincadifformine, has been isolated from Aspidosperma pyrifolium Mart. Moreover, 10 derivatives were preparedfrom the vincadifformine. The study was conducted to evaluate the in vitro antiplasmodial and cytotoxic activity ofthe vincadifformine and their semisynthetic derivatives. The in vitro antiplasmodial activity was evaluated onPlasmodium falciparum chloroquine-resistant (FcM ) and –sensitive (Nigerian) strains after 24-h and 72-h incubation, 29while cytotoxic activity was estimated on Hela cells and Cytotoxicity Index (CI = IC on HeLa cells/IC on FcM strain) 50 50 29was calculated to evaluate the safety of tested compounds. Experiment results showed that two compounds (4 and 8)exhibited good antiplasmodial activities in comparison with parent compound, vincadifformine and other testedcompounds with IC ranging from 5.3 to 12.8 μM on FcM strain and 11.4 to 24.0 μM on Nigerian strain. In addition, 50 29the CI of two compounds were also lower after 24-h incubation (CI, 2.0 and 4.8) than that of after 72-h incubation (CI,9.5 and 11.5). Further study will be conducted to evaluate quantitative structure-activity relationship (QSAR) in orderto design new antimalarial drugs.Keywords : vincadifformine - antiplasmodial – Plasmodium falciparum – cytotoxic - HeLa