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

Banfi, Felipe Finger; Krombauer, Gabriela Camila; Fonseca, Amanda Luisa da; Nunes, Renata Rachide; Andrade, Silmara Nunes; Rezende, Millena Alves de; Chaves, Mariana Helena; Filho, Evaldo dos Santos Monção; Taranto, Alex Guterres; Rodrigues, Domingos de Jesus; Júnior, Gerardo Magela Vieira; Castro, Whocely Victor de; Varotti, Fernando de Pilla; Sanchez, Bruno A. M.

doi:10.1590/1678-9199-jvatitd-2020-0073

Cited by 6 publications

(4 citation statements)

References 59 publications

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“…Three other bufadienolides, marinobufotoxin, marinobufagin, and bufalin, isolated from the secretion of R. marina were also documented of exhibiting anti-plasmodial activity against P. falciparum by interrupting the trophozoites development. The alkaloid dehydrobufotenine, isolated from the secretion of the same species also showed a strong inhibitory activity against the development of P. falciparum trophozoites (Ben et al 2021).…”

Section: Stage Speci City Assaymentioning

confidence: 98%

Antimalarial efficacy of Duttaphrynus melanostictus skin extract via inhibition of Plasmodium falciparum Na+/H+ ATPase

Bagwe,

D’Souza,

Sharma

2024

Preprint

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Malaria remains a major health issue worldwide that affects many people, particularly in developing nations. Since, the malarial parasite has developed resistance against nearly every antimalarial drug now in use, it is imperative to search for novel antimalarial medications. Toxins produced by skin glands of toads have been shown to possess antiparasitic properties against a variety of protozoan parasites because of the bufadienolides they contain. Even though several studies have been conducted to show that toad skin secretions have antimalarial properties, very little information is known about the precise mechanism by which they work against Plasmodium infection. Thus, the goal of this study was to evaluate the antiplasmodial activity of crude skin extracts from Common Asian Toads, Duttaphrynus melanostictus, of different sizes and illustrate how they work against Plasmodium falciparum 3D7 cells. The findings demonstrated a negative correlation between the toad size and percent yield of the extracts. HPTLC and UPLC-MS/MS analysis of the extracts exhibited varied composition of bufadienolides depending on the size of the animal. The extract obtained from small toads containing resibufagin and marinobufagin lactate demonstrated highest antiplasmodial activity and showed lowest cytotoxicity on peripheral blood mononuclear cells. It was discovered that the extract was effective against the trophozoite stage of the parasite. The extract was reported to inhibit Na+/H+ ATPase of Plasmodium by binding to sodium-enzyme complex at ATP binding site. The study offers baseline data that can be used to assess the antimalarial potential of individual components in the skin extract derived from small toads.

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Section: Stage Speci City Assaymentioning

confidence: 98%

Antimalarial efficacy of Duttaphrynus melanostictus skin extract via inhibition of Plasmodium falciparum Na+/H+ ATPase

Bagwe,

D’Souza,

Sharma

2024

Preprint

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“…The steroid telocinobufagin, isolated from the secretions of both toad species, showed antiplasmodial activity in vitro for P. falciparum by interfering with the development of trophozoites (IC 50 = 1280 µg/mL) [ 95 ]. Three other bufadienolides, marinobufotoxin, marinobufagin, and bufalin, were isolated from the secretion of R. marina and showed antiplasmodial activity in vitro for P. falciparum by interrupting the development of trophozoites (IC 50 = 5.31, 3.89 and 3.44 µg/mL, respectively) [ 122 ].…”

Section: Antiplasmodial Toxinsmentioning

confidence: 99%

“…Dendrobatidae presents the largest number of individuals known to have alkaloids in their toxins [ 86 , 118 ], the other families being Mantellidae, Eleutherodactylidae, Bufonidae, and Myobatrachidae. The alkaloid dehydrobufotenine, isolated from the secretion of the bufonid R. marina , was tested for antiplasmodial activity and showed great inhibitory activity against the development of P. falciparum trophozoites (IC 50 = 19.11 µg/mL) [ 122 ].…”

Section: Antiplasmodial Toxinsmentioning

confidence: 99%

Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review

Salimo

Barros

Adrião

et al. 2023

Toxins

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Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs.

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“…Thus, the virtual screening of potential antimalarial candidates was performed by using the BraMMT data bank [28]. Binding energy values, ∆ (binding energy of the crystallographic ligand-binding energy of the compound) values, were calculated [29], and these values were employed as a first step in the selection process applied to choose the most promising structures to be synthesized.…”

Section: Experimental Design 21 Virtual Screeningmentioning

confidence: 99%

Rational-Based Discovery of Novel β-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria

et al. 2022

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Malaria is an infectious disease widespread in underdeveloped tropical regions. The most severe form of infection is caused by Plasmodium falciparum, which can lead to development of cerebral malaria (CM) and is responsible for deaths and significant neurocognitive sequelae throughout life. In this context and considering the emergence and spread of drug-resistant P. falciparum isolates, the search for new antimalarial candidates becomes urgent. β-carbolines alkaloids are good candidates since a wide range of biological activity for these compounds has been reported. Herein, we designed 20 chemical entities and performed an in silico virtual screening against a pool of P. falciparum molecular targets, the Brazilian Malaria Molecular Targets (BRAMMT). Seven structures showed potential to interact with PfFNR, PfPK7, PfGrx1, and PfATP6, being synthesized and evaluated for in vitro antiplasmodial activity. Among them, compounds 3–6 and 10 inhibited the growth of the W2 strain at µM concentrations, with low cytotoxicity against the human cell line. In silico physicochemical and pharmacokinetic properties were found to be favorable for oral administration. The compound 10 provided the best results against CM, with important values of parasite growth inhibition on the 5th day post-infection for both curative (67.9%) and suppressive (82%) assays. Furthermore, this compound was able to elongate mice survival and protect them against the development of the experimental model of CM (>65%). Compound 10 also induced reduction of the NO level, possibly by interaction with iNOS. Therefore, this alkaloid showed promising activity for the treatment of malaria and was able to prevent the development of experimental cerebral malaria (ECM), probably by reducing NO synthesis.

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

Cited by 6 publications

References 59 publications

Antimalarial efficacy of Duttaphrynus melanostictus skin extract via inhibition of Plasmodium falciparum Na+/H+ ATPase

Antimalarial efficacy of Duttaphrynus melanostictus skin extract via inhibition of Plasmodium falciparum Na+/H+ ATPase

Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review

Rational-Based Discovery of Novel β-Carboline Derivatives as Potential Antimalarials: From In Silico Identification of Novel Targets to Inhibition of Experimental Cerebral Malaria

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