Dados do Trabalho

Título

Natural products as sources of new antimalarial molecules against Plasmodium vivax ex vivo

Introdução

The most common approaches for treating and controlling malaria are drug therapy and vector control with insecticides, respectively. However, according to studies conducted in Indonesia, Papua New Guinea, Brazil, Madagascar, Thailand, and Myanmar, P. vivax has developed resistance to currently used antimalarials. Consequently, studies to discover new antimalarial compounds are required. Natural products have drawn attention in recent decades as a potential source of novel antimalarial compounds.

Objetivo (s)

This work aimed to evaluate the antimalarial activity of natural products (bergenin, duguetin N-oxide, polycarpol, kaurenoic acid, ent-3β-acetoxy-kaur-16-ene, 16β-hydro-ent-kauran-17-oic and acanthoic acid) against P. vivax ex vivo.

Material e Métodos

This study was carried out at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) between 2022 and 2023. Ten milliliters of blood were obtained from 8 participants with P. vivax monoinfection (50% ring stage) and leukocyte depleted before plating on 96-well culture plates with the natural products (50 to 100 μg/mL). As controls, chloroquine (500 to 1000 ng/mL), DMSO solvent, untreated parasitized blood, and healthy red blood cells were used. Microscopy and flow cytometry were used to calculate the percentage P. vivax inhibition. Subsequently, IC50 (50% parasite inhibition) were calculated using the IC Estimator software v1.2. The IC50 data were analyzed with SPSS v.22, which used multivariate analysis of variance to compare IC50 between experimental conditions and as a Tukey's Test post hoc test.

Resultados e Conclusão

Compared to Chloroquine (IC50 434.24-435ng/mL), natural products significantly inhibited P. vivax growth in ex vivo cultures (P<0.05): Bergenin (IC50 41.06-41.66µg/mL), duguetin N-oxide (IC50 47.12-47.42µg/mL), polycarpol (IC50 46.85-47.28µg/mL), kaurenoic acid (IC50 41.37-42.88µg/mL), ent-3β-acetoxy-kaur-16-ene (IC50 47.27-48.05 µg/mL), 16β-hydro-ent-kauran-17-oic acid (IC50 41.41-43.19µg/mL), and acanthoic acid (IC50 48.02-50.34µg/mL). Between the IC50s values obtained by flow cytometry and optical microscopy, were no significant differences (P>0.05). Our findings suggest that the tested natural products are promising and can significantly inhibit the growth of P. vivax in ex vivo cultures. However, further research should be done to understand their mechanism of P. vivax inhibition, as this represents a major milestone against the backdrop of resistance to current antimalarials.

Palavras-chave

Plasmodium vivax; Ex vivo; Bergenin; Duguetin N-oxide; Polycarpol; Kaurenoic acid; Ent-3β-acetoxy-kaur-16-ene; 16β-hydro-ent-kauran-17-oic; Acanthoic acid.

Agradecimentos

Fundação de Amparo à Pesquisa do Estado de Amazonas (FAPEAM).