Natural and Semisynthetic Triterpenes from Combretum leprosum Mart. with Antiplasmodial Activity

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.

Bibliographic Details

Main Authors:	Passarini,Guilherme M., Ferreira,Amália S., Moreira-Dill,Leandro S., Zanchi,Fernando B., Jesus,Aurileya G. de, Facundo,Valdir A., Teles,Carolina B. G.
Format:	Digital revista
Language:	English
Published:	Sociedade Brasileira de Química 2022
Online Access:	http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532022000500483
Tags:	Add Tag No Tags, Be the first to tag this record!