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Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs

Felipe Finger Banfi1, Gabriela Camila Krombauer1, Amanda Luisa da Fonseca2, Renata Rachide Nunes2, Silmara Nunes Andrade2, Millena Alves de Rezende2, Mariana Helena Chaves3, Evaldo dos Santos Monção Filho3, Alex Guterres Taranto2, Domingos de Jesus Rodrigues4, Gerardo Magela Vieira Júnior3, Whocely Victor de Castro5, Fernando de Pilla Varotti2, Bruno Antonio Marinho Sanchez1 [ + show more ]

J Venom Anim Toxins incl Trop Dis, 2021, 27:e20200073
Received: 07 May 2020 | Accepted: 28 October 2020 | Published online: 08 January 2021


Background: The resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity in silico and in vitro of four compounds isolated from Rhinella marina venom as potential oral drug prototypes. Methods: Four compounds were challenged against 35 target proteins from P. falciparum and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and in silico assay in OCTOPUS® software. The in vitro antimalarial activity of the compounds against the 3D7 Plasmodium falciparum clones were assessed using the SYBR Green I based assay (IC50). For the cytotoxic tests, the LD50 was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Results: All compounds presented a ligand-receptor interaction with ten Plasmodium falciparum-related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC50 = 3.44 μM to 19.11 μM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite. Conclusions: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.


Keywords: Bufadienolides; Antimalarial drug; Docking; Natural compounds.

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