Avaliação de compostos isolados do fruto de Dipteryx lacunifera Ducke (Fabaceae) em ensaios in silico e in vitro como potenciais novos antimaláricos

Abstract

Resistance to the main drugs used nowadays in the treatment of malaria in humans is one of the main challenges for controlling the disease worldwide. Therefore, the discovery of alternative drugs that can effectively treat the disease is extremely urgent and important. Thus, the objective of this study was to evaluate the antimalarial and cytotoxic potential of 3 flavonoids isolated from the fruit of the species Dipteryx lacunifera, DFE 68-72 (3´, 4´. 7- trihydroxy flavone), DFE 68-14-19 (3´, 4´. 7- trihydroxiflavanone) and eriodicthiol using chemotherapy tests with Plasmodium falciparum strain W2, cytotoxicity tests (in vitro) and virtual molecular modeling platforms(in silico). The in vitro tests demonstrated that the DFE 68-14-19 compound showed the best results of 50% inhibitory concentration against P. falciparum W2 strain (IC50 = 7.35 μM), with low cytotoxicity against the human fibroblast strain (WI-26-VA4) 50% lethal concentration (LC50> 100 μM) and selectivity index (IS = 13.61). In the docking test, the three compounds promoted interaction indexes with 17 target proteins, related to P. falciparum (1LYX, 1NHW, 1O5X, TV5, 2OK8, 2PML, 2VFA, 2YOG, 3BPF, 3K7Y, 3PHC, 4C81, 4N0Z, 4P7S, 4QOX, PfATP6, PfHT). The in silico assay of physical-chemical evaluation predicted that the three compounds presented potential conditions for prototypes for oral drugs, with good prediction of absorption, permeability and absence of toxicity, according to the Lipinski, Gleeson, Hughes, Ghose, Veber, Egan e Muegge’s rules. With this study, a new molecule (DFE-68-14-19) was founded with antimalarial activity and absence of cytotoxicity in computational and biological tests, needing further studies.