Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs
Main Author: | |
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Publication Date: | 2021 |
Other Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | The Journal of venomous animals and toxins including tropical diseases (Online) |
Download full: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100301 |
Summary: | 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. |
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The Journal of venomous animals and toxins including tropical diseases (Online) |
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Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugsBufadienolidesAntimalarial drugDockingNatural compoundsAbstract 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.Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP)2021-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100301Journal of Venomous Animals and Toxins including Tropical Diseases v.27 2021reponame:The Journal of venomous animals and toxins including tropical diseases (Online)instname:Universidade Estadual Paulista (UNESP)instacron:UNESP10.1590/1678-9199-jvatitd-2020-0073info:eu-repo/semantics/openAccessBanfi,Felipe FingerKrombauer,Gabriela CamilaFonseca,Amanda Luisa daNunes,Renata RachideAndrade,Silmara NunesRezende,Millena Alves deChaves,Mariana HelenaMonção Filho,Evaldo dos SantosTaranto,Alex GuterresRodrigues,Domingos de JesusVieira Júnior,Gerardo MagelaCastro,Whocely Victor deVarotti,Fernando de PillaSanchez,Bruno Antonio Marinhoeng2021-01-22T00:00:00Zoai:scielo:S1678-91992021000100301Revistahttp://www.scielo.br/jvatitdPUBhttps://old.scielo.br/oai/scielo-oai.php||editorial@jvat.org.br1678-91991678-9180opendoar:2021-01-22T00:00The Journal of venomous animals and toxins including tropical diseases (Online) - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
title |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
spellingShingle |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs Banfi,Felipe Finger Bufadienolides Antimalarial drug Docking Natural compounds |
title_short |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
title_full |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
title_fullStr |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
title_full_unstemmed |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
title_sort |
Dehydrobufotenin extracted from the Amazonian toad Rhinella marina (Anura: Bufonidae) as a prototype molecule for the development of antiplasmodial drugs |
author |
Banfi,Felipe Finger |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
Bufadienolides Antimalarial drug Docking Natural compounds |
topic |
Bufadienolides Antimalarial drug Docking Natural compounds |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100301 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100301 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1678-9199-jvatitd-2020-0073 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP) |
publisher.none.fl_str_mv |
Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP) |
dc.source.none.fl_str_mv |
Journal of Venomous Animals and Toxins including Tropical Diseases v.27 2021 reponame:The Journal of venomous animals and toxins including tropical diseases (Online) instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
The Journal of venomous animals and toxins including tropical diseases (Online) |
collection |
The Journal of venomous animals and toxins including tropical diseases (Online) |
repository.name.fl_str_mv |
The Journal of venomous animals and toxins including tropical diseases (Online) - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
||editorial@jvat.org.br |
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1748958541028261888 |