Natural products have provided a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over two hundred alkaloids have been identified In extracts from amphibian skins. These include batracbotoxins, which are potent activators of sodium channels, histrionicotoxins, Which are noncompetitive blockers of nicotinic receptor channel complexes and of potassium channels, and pumiliotoxins, which have myotonic and cardiotonic activity (iii(- to inhibitory effects on closing of sodium channels. A variety of further alkaloids have, been characterized from dendrobatid frogs. These include new 2,5-disubstituted decahydroquinolizies 5,8-disubstited indolizidines, 6,9-disubstituted quinolizidines, 3,5-disubstituted pyrrolizidines, pumiliotoxins, homopumiliotoxins and allopumilliotoxins. Many of these alkaloids have activity as noncompetitive blockers at muscle-type and ganglionic-type nicotinic receptor-channels. Structures for three tricyclic pyrrolizidinone oximes and O-mothyloximes from a dendrobatid frog have been determined based on analysis by mass spectrometry, infrared spectroscopy and nuclear magnetic resonance spectrometry. A structure for the parent member (C(11)H(13)N(2)Cl(2) ) a new class of analgetic alkaloids has been similarly derived by analysis of an N-acetyl derivative. Characterization of alkaloids in nondendrobatid amphibians indicates that the biosynthetic pathways to certain dendrobatid alkaloids have evolved separately in one lineage (genus) of amphibians from the families Bufonidae, Myobatracidae and Ranidae and in a lineage leading to four genera in the family Dendrobatider. The lack of alkaloid production in captive-raised dendrobatid frogs now appears due to lack of natural environment and/or diet. A peptide (thirty amino acid residues) isolated from mucous secretions of a hylid frog Phyllomedusa bicolor causes profound behavioral depression land stimulates binding of adenosine agonists to brain A(1)-adenosine receptors.
| Spande, TF; Jain, P; Garraffo, HM et al. (1999) Occurrence and significance of decahydroquinolines from dendrobatid poison frogs and a myrmicine ant: use of 1H and 13C NMR in their conformational analysis J Nat Prod 62:5-21 |
| Garraffo, H M; Spande, T F; Jones, T H et al. (1999) Ammonia chemical ionization tandem mass spectrometry in structure determination of alkaloids. I. Pyrrolidines, piperidines, decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines and an azabicyclo[5.3.0]decane. Rapid Commun Mass Spectrom 13:1553-63 |
