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

Abstract

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.

Combretum leprosum Mart.: Botany, Ethnomedicinal Uses, Biological Activities, Phytochemistry and Conservation Needs

“…The results showed that natural triterpenes isolated from C. leprosum have antimalarial and antiplasmodial activity, which may represent an important tool in the development of drugs associated with the treatment of malaria (Passarini et al, 2022). In addition to the antimalarial application, Araújo et al (2021) associate the use of 3β, 6β, 16β-trihydroxylup-20(29)ene in the treatment against T. cruzi, being observed that the compound is well absorbed in the test organism and presents low toxicity, being able to be a candidate in the developed of new options for the treatment of Chagas disease.…”