RESUMO
Bufonid toads of the genus Melanophryniscus represent one of several lineages of anurans with the ability to sequester alkaloids from dietary arthropods for chemical defense. The alkaloid profile for Melanophryniscus stelzneri from a location in the province of Córdoba, Argentina, changed significantly over a 10-year period, probably indicating changes in availability of alkaloid-containing arthropods. A total of 29 alkaloids were identified in two collections of this population. Eight alkaloids were identified in M. stelzneri from another location in the province of Córdoba. The alkaloid profiles of Melanophryniscus rubriventris collected from four locations in the provinces of Salta and Jujuy, Argentina, contained 44 compounds and differed considerably between locations. Furthermore, alkaloid profiles of M. stelzneri and M. rubriventris strongly differed, probably reflecting differences in the ecosystem and hence in availability of alkaloid-containing arthropods.
Assuntos
Alcaloides/análise , Animais , Argentina , Artrópodes , Bufonidae , Dieta , Especificidade da EspécieRESUMO
The structure of alkaloid 223A (1), the first member of a new class of amphibian alkaloids, purified by HPLC from a skin extract of a Panamanian population of the frog Dendrobates pumilio Schmidt (Dendrobatidae) has been established as (5R,6S,8R,9S)- or (5S,6R,8S,9R)-6,8-diethyl-5-propylindolizidine, based on GC-MS, GC-FTIR, and 1H-NMR spectral studies. Three higher homologs of 223A, namely alkaloids 237L (2), 251M (3), and 267J (4), have been detected in other extracts, and tentative structures are proposed.
Assuntos
Anuros/metabolismo , Indolizinas/química , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Indolizinas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Panamá , Pele/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Amphibian skin has provided a wide range of biologically active alkaloids, many of which have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified and structures of over a dozen different classes of alkaloids have been elucidated. These include the batrachotoxins, which were shown to be potent and selective activators and ligands for sodium channels, the histrionicotoxins, which were shown to be potent non-competitive blockers and ligands for nicotine receptor channel complexes, the pumiliotoxins and related allo- and homo-pumiliotoxins, which were shown to have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, which was shown to have potent antinociceptive activity due to selective agonist activity at nicotinic receptors. These alkaloids are known in nature only in amphibian skin, except for homobatrachotoxin, which was recently identified in feathers and skin of a bird. Further classes of alkaloids from amphibian skin include monocyclic pyrrolidines and piperidines, bicyclic decahydroquinolines, pyrrolizidines, indolizidines, and quinolizidines and tricyclic gephyrotoxins, pyrrolizidine oximes, pseudophrynamines, and coccinellines. These alkaloids also have activity in ion channels. It appears likely that all of the frog skin alkaloids are taken up and sequestered into the skin from the diet, which for such amphibians consists mainly of small arthropods. The pyrrolidines, piperidines, 3,5-disubstituted pyrrolizidines and 3,5-disubstituted indolizidines appear likely to be derived from ants, the coccinellines and related tricyclics from beetles and the pyrrolizidine oximes from millipedes. The origins of the batrachotoxins, histrionicotoxins, pumiliotoxins and epibatidine are of particular interest in view of their remarkable biological activities.
Assuntos
Alcaloides/metabolismo , Anuros/fisiologia , Batraquiotoxinas/fisiologia , Receptores Nicotínicos/fisiologia , Pele/metabolismo , Canais de Sódio/fisiologia , Animais , Cromatografia GasosaRESUMO
Amphibian skin has provided a wide range of biologically active alkaloids, many of wich have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified and structures of over a dozen different classes of alkaloids have been elucidated. These iclude the batrachotoxins, wich were shown to be potent and selective activators and ligands for sodium channels, the histrionicotoxins, wich were shoen to be potent non-competitive blockers and ligands for nicotine receptor channel complexes, the pumiliotoxins and related allo-and homo-pumiliotoxins, wich were shown to have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, wich was shown to have potent antinociceptive activity due to selective agonist activity at nicotinic receptors. These alkaloids are known in nature only in amphibian skin, except for homobatrachotoxin, wich was recently identified in feathers and skin of a bird. Further classes of alkaloids from amphibian skin include monocyclic pyrrolidines and piperidines, bicyclic decahydroquinolines, pyrrolizidines, and quinolozidines and tricyclic gephyrotoxins, pyrrolizidine oximes, etc..
Assuntos
Animais , Alcaloides/farmacologia , Batraquiotoxinas/química , Canais de Sódio , Receptores Nicotínicos/fisiologia , Pele/química , Anuros , Batraquiotoxinas/metabolismo , Cromatografia GasosaRESUMO
A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as Phyllomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to A1 adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans.
Assuntos
Proteínas de Anfíbios , Peptídeos Catiônicos Antimicrobianos , Anuros/fisiologia , Indígenas Sul-Americanos , Magia , Peptídeos/farmacologia , Receptores Purinérgicos/efeitos dos fármacos , Pele/metabolismo , Sequência de Aminoácidos , Animais , Ligação Competitiva , Encéfalo/metabolismo , Brasil , Membrana Celular/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/isolamento & purificação , Peptídeos/metabolismo , Peru , Fenilisopropiladenosina/metabolismo , Ratos , Receptores Purinérgicos/metabolismoRESUMO
Dendrobatid frogs produce a diverse set of alkaloids, whose profiles appear characteristic of frogs of each species or, in the case of variable species, of each population. In the case of one widespread species, Dendrobates auratus, alkaloid profiles in extracts of skin are markedly different in three populations, one from a Pacific island, Isla Taboga, Panama, one from central mountains in Panama, and the third from the Caribbean coast in Costa Rica. The first contains three major classes of dendrobatid alkaloids, the histrionicotoxins, the pumiliotoxin-A class and the decahydroquinolines. The second contains mainly histrionicotoxins, pumiliotoxin-A class alkaloids and one indolizidine. The third contains histrionicotoxins, a homopumiliotoxin, one decahydroquinoline, and a variety of indolizidines, quinolizidines and pyrrolizidines. Frogs from Isla Taboga or a nearby island were introduced into the Manoa Valley, Oahu, Hawaii, in 1932. Remarkably, although alkaloids of the pumiliotoxin-A class and one decahydroquinoline are still major constituents in skin extracts of Hawaiian frogs descended from the 1932 founding population, histrionicotoxins are absent and a novel tricyclic alkaloid is present. Offspring of wild-caught parents from Hawaii, Panama or Costa Rica raised in indoor terrariums on a diet of crickets and fruit flies do not contain detectable amounts of skin alkaloids. Offspring raised in large outside terrariums in Hawaii and fed mainly wild-caught termites and fruit flies do contain the same profile of alkaloids as their wild-caught parents in Hawaii, but at reduced levels. The genetic, environmental and dietary determinants of alkaloid profiles in dendrobatid frogs remain obscure, in particular the underlying cause for total absence in terrarium-reared frogs.
Assuntos
Alcaloides/química , Genética Populacional , Venenos/química , Ranidae/metabolismo , Alcaloides/isolamento & purificação , Animais , Costa Rica , Dieta , Ecologia , Havaí , Panamá , Venenos/isolamento & purificação , Pele/químicaRESUMO
Alkaloids of a new class are present in skin extracts of the dendrobatid poison frog, Minyobates bombetes, of Colombia. The structure of the major alkaloid of this class, 251F, has been determined as a trimethylcyclopenta[b]quinolizidinemethanol 1 by nmr, gc-Ft-ir, and ms studies including ms-ms. At least nine congeners of 251F were detected in these extracts.
Assuntos
Alcaloides/análise , Anuros/metabolismo , Alcaloides/química , Animais , Colômbia , Espectrometria de Massas , Pele/químicaRESUMO
Several taxa of small frogs from the southern hemisphere contain alkaloids similar or identical to compounds previously known only from neotropical poison frogs of the family Dendrobatidae. Skin of the Brazilian toad Melanophryniscus moreirae (family Bufonidae) contains a new alkaloid 8-hydroxy-8-methyl-6-(5'-hydroxy-2'-methyl-hexylidene)-1-azabicycl o-[4.3.0] nonane (C16H29NO2), which is designated pumiliotoxin 267C. Such a structure is typical of the pumiliotoxin-A class of dendrobatid alkaloids. Melanophyryniscus moreirae contains smaller quantities of an alkaloid (C19H33NO3) identical in chromatographic and mass spectral properties to the dendrobatid alkaloid allopumiliotoxin 323B. Allopumiliotoxin 323B and an isomer of 267C occur with unidentified alkaloids in skin of the Australian frog Pseudophryne semimarmorata (family Myobatrachidae) and also in the skin of the Madagascan frog Mantella aurantiaca (family Ranidae, subfamily Mantellinae). In addition to new compounds, Mantella aurantiaca and M. madagascariensis also contain other alkaloids (e.g. histrionicotoxin and pumiliotoxin B) that were known previously only in dendrobatid frogs. Such alkaloids have not been detected in a phylogenetically wide array of other anuran amphibians, and the dendrobatid alkaloids thus become an evolutionary enigma. Certain of these compounds may have arisen convergently from new biosynthetic pathways in several families of frogs, or these alkaloids may represent parallel expression of shared-primitive pathways that are unexpressed or lost in related frogs.
Assuntos
Alcaloides/análise , Anuros/metabolismo , Pele/análise , Animais , Austrália , Brasil , Bufonidae/metabolismo , Fenômenos Químicos , Química , Cromatografia Gasosa/métodos , Cromatografia em Camada Fina/métodos , Madagáscar , Espectroscopia de Ressonância Magnética , Ranidae/metabolismo , Especificidade da EspécieRESUMO
The structures and absolute configuration of two unique alkaloids isolated from the Colombian frog, Dendrobates histrionicus, have been elucidated by Roentgen-ray (x-ray) crystallography. Histrionicotoxin is (2pR, 6S, 7pS, 8aS)-7-(cis-1-buten-3-ynyl)-8-hydroxy-2-(cis-2-penten-4- ynyl)-1-azaspiro[5.5] undecane, while in dihydro-isohistrionicotoxin the acetylenic 2-pentenynyl side chain is replaced by an allenic 2-(3,4 pentadienyl) substituent. Dendrobates histrionicus exhibits remarkable interpopulational variations in amounts and composition of skin toxins, in behavior, and in phenotypic characters, aspects of which are illustrated in a color plate. The histrionico-toxins are the third class of alkaloids isolated from the defensive skin secretions of Neotropical (Dendrobatidae) frogs.
Assuntos
Alcaloides/isolamento & purificação , Anuros/análise , Pele/análise , Toxinas Biológicas/isolamento & purificação , Animais , Cromatografia , Cor , Modelos Estruturais , Peso Molecular , Fenótipo , Difração de Raios XRESUMO
A small Neotropical frog, Dendrobates pumilio, undergoes interpopulational variation in color, degree of toxicity, size, and habits. Differences in body coloration encompass the visible spectrum from red to blue, as well as achromatic black and white. There are wide variations in the degree of toxicity, but these variations are not correlated with supposed warning colors. Extracts of skin yield two toxic compounds characterized as steroidal alkaloids with molecular formulae C(19)H(33)NO(2) and C(l9)H(33)NO(3). The rapid rate of divergent evolution among populations of this frog may result from isolation and chance restriction of original heterozygosity, with subsequent selection acting on different and greatly limited mixtures of alleles.