Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella alata (Anura: Bufonidae): Antiprotozoal Activity against Trypanosoma cruzi

Rodríguez, Candelario; Ibáñez, Roberto; Mojica, Luis; Ng, Michelle; Spadafora, Carmenza; Durant-Archibold, Armando A.; Gutiérrez, Marcelino

doi:10.3390/molecules26144217

Cited by 12 publications

(10 citation statements)

References 39 publications

(55 reference statements)

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“…All four compounds were also shown to have minimum cytotoxicity in human intestinal cells (HCT-8). Earlier report mentioned that bufotalin has modest cytotoxicity in mammals and was active against trypanosomiasis [ 28 ]. Also, bufotalin effectively suppressed the growth of xenografted R-HepG2 cells in an in vivo investigation, with minimal body weight loss or spleen toxicity [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potent anti-Cryptosporidium new drug leads by screening traditional Chinese medicines

et al. 2022

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Cryptosporidium spp. are gastrointestinal opportunistic protozoan parasites that infect humans, domestic animals, and wild animals all over the world. Cryptosporidiosis is the second leading infectious diarrheal disease in infants less than 5 years old. Cryptosporidiosis is a common zoonotic disease associated with diarrhea in infants and immunocompromised individuals. Consequently, cryptosporidiosis is considered a serious economic, veterinary, and medical concern. The treatment options for cryptosporidiosis are limited. To address this problem, we screened a natural product library containing 87 compounds of Traditional Chinese Medicines for anti-Cryptosporidium compounds that could serve as novel drug leads and therapeutic targets against C. parvum. To examine the anti-Cryptosporidium activity and half-maximal inhibitory doses (EC50) of these compounds, we performed in vitro assays (Cryptosporidium growth inhibition assay and host cell viability assay) and in vivo experiments in mice. In these assays, the C. parvum HNJ-1 strain was used. Four of the 87 compounds (alisol-A, alisol-B, atropine sulfate, and bufotalin) showed strong anti-Cryptosporidium activity in vitro (EC50 values = 122.9±6.7, 79.58±13.8, 253.5±30.3, and 63.43±18.7 nM, respectively), and minimum host cell cytotoxicity (cell survival > 95%). Furthermore, atropine sulfate (200 mg/kg) and bufotalin (0.1 mg/kg) also showed in vivo inhibitory effects. Our findings demonstrate that atropine sulfate and bufotalin are effective against C. parvum infection both in vitro and in vivo. These compounds may, therefore, represent promising novel anti-Cryptosporidium drug leads for future medications against cryptosporidiosis.

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Section: Discussionmentioning

confidence: 99%

Identification of potent anti-Cryptosporidium new drug leads by screening traditional Chinese medicines

et al. 2022

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“…Bufotalin and cinobufagin (IC 50 8.713 and 12.833 μg/mL against T. cruzi ) presented low cytotoxicity (LD 50 20.446 and 23.897 μg/mL) in epithelial kidney monkey Vero cells (ATCC) [ 11 ].…”

Section: Antimicrobial Activities Of Compounds From Toads’ Cutaneous ...mentioning

confidence: 99%

“…The first type is associated with respiration and hydration, while the parotoid glands secrete components related to defense, providing protection against predators and microorganisms [ 3 , 4 , 5 , 6 ]. These secretions consist of a complex composition of biomolecules containing alkaloids (dehydrobufotenine, atelopidtoxin, bufothionine, pumiliotoxin), biogenic amines (adrenaline, dopamine, serotonin), steroids (arenobufagin, Gamma-bufotalin, resibufogenin, telocinobufagin), peptides (alyteserin 1C, Bv8, cathelicidin), proteins, and others [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. These components have various biological activities: antibacterial, anticancer, antifungal, anti-inflammatory, antiprotozoal, antitumoral, antiviral, insecticidal, and immunomodulatory [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial Compounds from Skin Secretions of Species That Belong to the Bufonidae Family

Ibarra-Vega

Salazar-Monge

Zatarain-Palacios

et al. 2023

Toxins

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Skin secretions of toads are a complex mixture of molecules. The substances secreted comprise more than 80 different compounds that show diverse pharmacological activities. The compounds secreted through skin pores and parotid glands are of particular interest because they help toads to endure in habitats full of pathogenic microbes, i.e., bacteria, fungi, viruses, and protozoa, due to their content of components such as bufadienolides, alkaloids, and antimicrobial peptides. We carried out an extensive literature review of relevant articles published until November 2022 in ACS Publications, Google Scholar, PubMed, and ScienceDirect. It was centered on research addressing the biological characterization of the compounds identified in the species of genera Atelopus, Bufo, Duttaphrynus, Melanophryniscus, Peltopryne, Phrynoidis, Rhaebo, and Rhinella, with antibacterial, antifungal, antiviral, and antiparasitic activities; as well as studies performed with analogous compounds and skin secretions of toads that also showed these activities. This review shows that the compounds in the secretions of toads could be candidates for new drugs to treat infectious diseases or be used to develop new molecules with better properties from existing ones. Some compounds in this review showed activity against microorganisms of medical interest such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Coronavirus varieties, HIV, Trypanosoma cruzi, Leishmania chagasi, Plasmodium falciparum, and against different kinds of fungi that affect plants of economic interest.

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“…Bufonid toads produce steroid toxins called bufadienolides in granular glands of their skin from early larval development (Clarke, 1997; Hayes et al., 2009; Toledo & Jared, 1995; Ujszegi et al., 2017; Üveges et al., 2017). Bufadienolides do not only deter various predators (Hayes et al., 2009; Toledo & Jared, 1995) but may also show antimicrobial, antiprotozoal, and antifungal activity, providing some level of protection against pathogens and parasites, including Bd (Barnhart et al., 2017; Cunha Filho et al., 2005; Rodriguez et al., 2020, 2021; Tempone et al., 2008). Bufadienolide synthesis is a flexible trait, which is influenced by anthropogenic habitat change and pollution (Bókony et al., 2017, 2019), the presence of predators or competitors (Benard & Fordyce, 2003; Bókony et al., 2016, 2018; Hagman et al., 2009; Üveges et al., 2017, 2021), food availability (Üveges et al., 2017), and the age of individuals (Ujszegi et al., 2017, 2021; Üveges et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Metamorphic common toads keep chytrid infection under control, but at a cost

et al. 2022

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Batrachochytrium dendrobatidis (Bd) causes chytridiomycosis, an infectious disease of amphibians, which has contributed to population declines in hundreds of species worldwide. Common toads (Bufo bufo) exhibit low resistance and relatively high tolerance to Bd infection, which may partly be attributable to bufadienolide toxins secreted in their granular skin glands. Bufadienolides are known to provide an effective defense against several pathogens, parasites, and predators. The toxin production of bufonids is a plastic trait, inducible by several environmental factors. Here, we experimentally infected juvenile common toads with Bd and investigated if the toadlets could clear the infection over time, whether the infection induced bufadienolide production, and whether the infection caused decreased body mass. We found that prevalence remained 100% throughout the entire experimental period, but infection intensity did not increase and it was significantly lower on day 30 than on day 20. At the same time, compared to controls, infected toadlets produced lesser amounts of bufadienolides and their body mass was also lower. These results suggest that although young toadlets may not be able to clear Bd infection on their own, they may be able to keep infection intensities under control. Nonetheless, even if toadlets do not succumb to the disease, the costs of chronic infection may still compromise their fitness.We used the H-2014 BdGPL isolate obtained from a living specimen of Bombina variegata co-occurring with B. bufo in the Pannonian Basin (Bakony Mountains

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Bufadienolides from the Skin Secretions of the Neotropical Toad Rhinella alata (Anura: Bufonidae): Antiprotozoal Activity against Trypanosoma cruzi

Cited by 12 publications

References 39 publications

Identification of potent anti-Cryptosporidium new drug leads by screening traditional Chinese medicines

Identification of potent anti-Cryptosporidium new drug leads by screening traditional Chinese medicines

Antimicrobial Compounds from Skin Secretions of Species That Belong to the Bufonidae Family

Metamorphic common toads keep chytrid infection under control, but at a cost

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