Natural and Semisynthetic Triterpenes from Combretum leprosum Mart. with Antiplasmodial Activity
AUTOR(ES)
Passarini, Guilherme M.; Ferreira, Amália S.; Moreira-Dill, Leandro S.; Zanchi, Fernando B.; Jesus, Aurileya G. de; Facundo, Valdir A.; Teles, Carolina B. G.
FONTE
Journal of the Brazilian Chemical Society
DATA DE PUBLICAÇÃO
2022
RESUMO
Malaria is responsible for thousands of deaths each year. Currently, artemisinin combination therapy (ACT) is used as first-choice medication against the disease. However, the emergence of resistant strains prompts the search for alternative compounds. The present study aimed to investigate the antiplasmodial activities of natural triterpenes (compounds 1 and 2), and semisynthetic derivatives 1a, 1b, 1c, and 1d. Antiplasmodial assays were carried out using the SYBR Green technique, whereas cytotoxicity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Hemolytic assays were performed on human erythrocytes. An in silico analysis of the compounds against PfENR (Plasmodium falciparum 2-trans-enoyl-reductase) was carried out by molecular docking. Experiments with 1, and its derivatives against P. falciparum showed that 1a was very similar in terms of biological activity to compound 1 (half maximal inhibitory concentration (IC50) ca. 4 µM), whereas 1b, 1c, and 1d had reduced antiplasmodial activities (IC50 between 8-103 µM). The selectivity indexes of 1 and 1d for HepG2, and Vero cells were > 10. Docking results partially agreed with the in vitro experiments, with 1 and 1c having the best and worst affinities with PfENR, respectively. In conclusion, the results showed that 1 and 1d may serve as biotechnological tools in the development of antimalarial drugs.
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