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 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.
Main Authors: | Banfi,Felipe Finger, Krombauer,Gabriela Camila, Fonseca,Amanda Luisa da, Nunes,Renata Rachide, Andrade,Silmara Nunes, Rezende,Millena Alves de, Chaves,Mariana Helena, Monção Filho,Evaldo dos Santos, Taranto,Alex Guterres, Rodrigues,Domingos de Jesus, Vieira Júnior,Gerardo Magela, Castro,Whocely Victor de, Varotti,Fernando de Pilla, Sanchez,Bruno Antonio Marinho |
---|---|
Format: | Digital revista |
Language: | English |
Published: |
Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP)
2021
|
Online Access: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100301 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Similar Items
-
Interspecific amplexi between two sympatric species of toads, Rhinella major and Rhinella marina (Anura: Bufonidae)
by: Costa-Campos,Carlos Eduardo, et al.
Published: (2016) -
Population traits of the burrowing toad Rhinella fernandezae (Gallardo, 1957) (Anura, Bufonidae)
by: Sanchez,LC., et al.
Published: (2008) -
Community of helminth parasites of thorny toad Rhinella Spinulosa (Anura: Bufonidae) of Peru
by: Chero, Jhon, et al.
Published: (2016) -
Action of heparin and acetylcholine modulators on the neurotoxicity of the toad Rhinella schneideri (Anura: Bufonidae) in Brazil
by: Rostelato-Ferreira,Sandro, et al.
Published: (2021) -
New species of beaked toad, Rhinella (Anura: Bufonidae), from the State of Bahia, Brazil
by: Caramaschi,Ulisses
Published: (2012)