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


ABSTRACT:

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 ?M to 19.11 ?M). 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.

SUBMITTER: Banfi FF 

PROVIDER: S-EPMC7812938 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Banfi Felipe Finger FF   Krombauer Gabriela Camila GC   da Fonseca Amanda Luisa AL   Nunes Renata Rachide RR   Andrade Silmara Nunes SN   de Rezende Millena Alves MA   Chaves Mariana Helena MH   Monção Evaldo Dos Santos EDS   Taranto Alex Guterres AG   Rodrigues Domingos de Jesus DJ   Vieira Gerardo Magela GM   de Castro Whocely Victor WV   Varotti Fernando de Pilla FP   Sanchez Bruno Antonio Marinho BAM  

The journal of venomous animals and toxins including tropical diseases 20210108


<h4>Background</h4>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  ...[more]

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