Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over five hundred alkaloids have been identified in extracts from amphibian skins. These include batrachotoxins, which are potent activators of sodium channels, histrionicotoxins, which are noncompetitive blockers of nicotinic receptor-channels and potassium channels, pumiliotoxins/allopumiliotoxins and related homopumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, an extremely potent and selective nicotinic agonist with potent antinociceptive activity. Further alkaloids include decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines, an unprecedented class of disubstituted azabicylo[5.3.0]decanes (lehmizidines), and a variety of tricylic alkaloids, including pyrrolizidine oximes, gephyrotoxins, pseudophrynamines, cyclopentaquinolizidines, coccinellines and coccinelline analogs. Lipophilic alkaloids occur in skins from four genera of neotropical dendrobatid frogs, in skins from one genus of Australian myobatrachid frogs, one genus of South American bufonid toads and one genus of Madagascan mantellid frogs. Virtually all frog skin alkaloids appear to have a dietary origin (ants, beetles, millipedes and other arthropods), being taken up and sequestered unchanged into skin glands. A remarkable exception appears to be the presence of a specific pumiliotoxin-7-hydroxylase activity in frogs of the genus Dendrobates. In addition, the pseudophrynamines, a class of indolic alkaloids found only in myobatrachid frogs of Australia, are produced by the frogs themselves, while their uptake system appears to be selective for certain pumiliotoxins/allopumiliotoxins, the only other class of alkaloids found in skin of these frogs. """"""""Combinatorial bioprospecting"""""""" has revealed that 5,8-disubstituted indolizidines, pumiliotoxins and allopumiliotoxins have a dietary arthropod source. Structures are under investigation for further novel alkaloids. Batrachotoxins also occur in skin and feathers of certain birds. Extracts and natural and synthetic alkaloids are being prepared from investigation in a variety of biological systems.
| Smith, B P; Tyler, M J; Kaneko, T et al. (2002) Evidence for biosynthesis of pseudophrynamine alkaloids by an Australian myobatrachid frog (pseudophryne) and for sequestration of dietary pumiliotoxins. J Nat Prod 65:439-47 |
| Dumbacher, J P; Spande, T F; Daly, J W (2000) Batrachotoxin alkaloids from passerine birds: a second toxic bird genus (Ifrita kowaldi) from New Guinea. Proc Natl Acad Sci U S A 97:12970-5 |
