Antiproliferative activity and chemical composition of the venom from the Amazonian toad Rhinella marina (Anura: Bufonidae)

Schmeda-Hirschmann, Guillermo; Quispe, Cristina; Vargas-Arana, Gabriel; Theoduloz, Cristina; Urra, Félix A.; Cárdenas, César

doi:10.1016/j.toxicon.2016.09.004

Cited by 41 publications

(45 citation statements)

References 31 publications

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“…Table S1. Those data were in agreement with earlier published data for Telocinobufagin-3-suberoyl-l-arginine [24].…”

Section: Structural Identificationsupporting

confidence: 93%

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An efficient strategy based on liquid‐liquid extraction and pH‐zone‐refining counter‐current chromatography for selective enrichment, separation, and purification of alkaloids and organic Acids from natural products

et al. 2020

J of Separation Science

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This study presents an efficient strategy based on liquid‐liquid extraction and pH‐zone‐refining counter‐current chromatography for selective enrichment, separation, and purification of alkaloids and organic acids from natural products. First, an acid or base modified two‐phase solvent system with maximum or minimum partition coefficient was developed for the liquid‐liquid extraction of the crude extract. As a result, alkaloids or organic acids could be selectively enriched in the upper or lower phase. Then pH‐zone‐refining counter‐current chromatography was employed to separate and purify the selectively enriched alkaloids or organic acids efficiently. The selective enrichment and separation of five bufadienolide from toad venom of Bufo marinus was used as an example to show the advantage of this strategy. As a result, 759 mg of selectively enriched bufadienolide was obtained from 2 g of crude extract and the total content of five targets was increased from 14.64 to 83%. A total of 31 mg of marinobufagin‐3‐adipoyl‐l‐arginine, 42 mg of telocinobufagin‐3‐pimeloyl‐l‐arginine, 51 mg of telocinobufagin‐3‐suberoyl‐l‐arginine, 132 mg of marinobufagin‐3‐suberoyl‐l‐arginine, and 57 mg of bufalin‐3‐suberoyl‐l‐arginine were all simultaneously separated from 500 mg of selectively enriched sample, with the purity of 92.4, 97.5, 90.3, 92.1, and 92.8%, respectively.

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“…Table S1. Those data were in agreement with earlier published data for Telocinobufagin-3-suberoyl-l-arginine [24].…”

Section: Structural Identificationsupporting

confidence: 93%

“…Toad venom of Bufo marinus are bioactive substances to treat toothaches, heart failure, and also act as chemical defensive toxin for predators [24,25]. Chemical bioactive substances detected or isolated in toad venom include bufadienolides, indole alkaloids, peptides, etc.…”

Section: Introductionmentioning

confidence: 99%

An efficient strategy based on liquid‐liquid extraction and pH‐zone‐refining counter‐current chromatography for selective enrichment, separation, and purification of alkaloids and organic Acids from natural products

et al. 2020

J of Separation Science

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show abstract

“…The m/z ratio of parent ion, the relative abundance and the eluting order matched the already published research work mentioned above. Previous chromatographic analyses also showed improper chromatograms with overlapping peaks between bufotoxins and bufogenins, even with slow organic gradients [25,27,36,38]. Co-elution of bufogenins and bufotoxins is also observed on the chromatogram obtained after UHPLC-UV analysis of our crude toad venom extract.…”

Section: Hplc Fractionationmentioning

confidence: 55%

“…A last bufagenin coelutes at Rt = 3.5 min and corresponds to arenobufagin, but became visible only when bufotoxins were removed by SPE. Preliminary peaks identification was based on parent ion [M+H + ] mass to charge ratio compared to published detailed LC-QTOF and HPLC-ESI-MS/MS analyses of several Rhinella marina (L.) toad F I G U R E 2 TLC plates obtained after migration of Bufo marinus toad extracts in several conditions as presented in Section 3.1 and Table 1: [25][26][27][35][36][37][38]. The m/z ratio of parent ion, the relative abundance and the eluting order matched the already published research work mentioned above.…”

Section: Hplc Fractionationmentioning

confidence: 99%

Marinobufagenin extraction from Rhinella marina toad glands: Alternative approaches for a systematized strategy

Lenaerts

Wells

Hambye

et al. 2019

J of Separation Science

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Marinobufagenin is a bufadienolide compound detected mainly in skin and parotoid gland secretions of Rhinella marina (L.) toad. Bufadienolides regulate the Na+/K+‐ATPase pump by inhibiting the cardiotonic steroid dependent‐site and act as cardiac inotropes with vasoconstrictive properties. Marinobufagenin and other bufadienolides, such as telocinobufagin and bufalin, are thought to be found endogenously in mammals in salt‐sensitive hypertensive states such as essential hypertension, congestive heart‐failure, and preeclampsia. The role of marinobufagenin as antimicrobial agent and its cytotoxic potential have also been recognized. The particular interest around marinobufagenin prompts us to consider the Rhinella marina toad venom as a possible source for molecules with pharmacological and/or diagnostic potential. In this article, two different approaches of extraction and purification of marinobufagenin from Rhinella marina (L.) venom are studied: (i) Preparative thin‐layer chromatography combined to mass spectrometry and/or ultraviolet detection and (ii) solid‐phase extraction coupled with fractionation on high‐performance liquid chromatography. Different chromatographic conditions are tested for each approach. The solid‐phase extraction combined with high‐performance liquid chromatography fractionation approach was preferred as it offered a greater yield, was less time‐consuming and allowed us to selectively isolate marinobufagenin. Both protocols aim to provide efficient and convenient methods for toad venom extraction, based on an easily automatable and systematized strategy.

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“…The parotoid poison is released as mechanism of defense against predators and microorganism infestation (Monti & Cardello, 1994). The parotoid gland of R. schneideri is a rich source of cardiotonic steroids known as bufadienolides, including "marinobufagin, bufalin, telocinobufagin, hellebrigenin, and the atypical 20S,21R-epoxymarinobufagin", and a great number of studies on the biological activities of skin secretions of R. schneideri (Cunha-Filho et al, 2010) and other species refer to their anti-proliferative and cytotoxic activities in different cancer cells lines (Ferreira et al, 2013;Schmeda-Hirschmann, Quispe, Theoduloz, de Sousa, & Parizotto 2014, Schmeda-Hirschmann et al, 2016.…”

mentioning

confidence: 99%

Methanolic extract of Rhinella schneideri (cururú toad) poison crude cause ultrastructural changes in nerve terminals of mouse phrenic nerve-diaphragm preparations

Rostelato‐Ferreira

Rocha²,

Belo³

et al. 2018

RBT

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Rhinella schneideri (or Bufo paracnemis), popularly known in Brazil as cururu toad, is also found in other countries in South America. The cardiovascular effects of this poison are largely known and recently was shown that it is capable to affect the neuromuscular junction on avian and mice isolated preparation. In this work, we used transmission electron microscopy to investigate the ultrastructure of the motor nerve terminal and postsynaptic junctional folds of phrenic nerve-hemidiaphragm preparations incubated for either 5 or 60 min with the methanolic extract of R. schneideri (50 µg/mL). In addition, the status of the acetylcholine receptors (AChR) was examined by TRITC-α-bungarotoxin immunofluorescence location at the endplate membrane. The results show that 5 min of incubation with the gland secretion extract significantly decreased (32 %) the number of synaptic vesicles into the motor nerve terminal, but did not decrease the electron density on the top of the junctional folds where nicotinic receptors are concentrated; however, 60 min of incubation led to significant nerve terminal reloading in synaptic vesicles whereas the AChR immunoreactivity was not as marked as in control and after 5 min incubation. Muscle fibers were well-preserved but intramuscular motor axons were not. The findings corroborated pharmacological data since the decrease in the number of synaptic vesicles (5 min) followed by recovery (60 min) is in accordance with the transient increase of MEPPs frequency meaning increased neurotransmitter release. These data support the predominant presynaptic mode of action of the R. schneideri, but do not exclude the possibility of a secondary postsynaptic action depending on the time the preparation is exposed to poison.

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Antiproliferative activity and chemical composition of the venom from the Amazonian toad Rhinella marina (Anura: Bufonidae)

Cited by 41 publications

References 31 publications

An efficient strategy based on liquid‐liquid extraction and pH‐zone‐refining counter‐current chromatography for selective enrichment, separation, and purification of alkaloids and organic Acids from natural products

An efficient strategy based on liquid‐liquid extraction and pH‐zone‐refining counter‐current chromatography for selective enrichment, separation, and purification of alkaloids and organic Acids from natural products

Marinobufagenin extraction from Rhinella marina toad glands: Alternative approaches for a systematized strategy

Methanolic extract of Rhinella schneideri (cururú toad) poison crude cause ultrastructural changes in nerve terminals of mouse phrenic nerve-diaphragm preparations

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