Alkaloids in Madagascan Frogs (Mantella): Pumiliotoxins, Indolizidines, Quinolizidines, and Pyrrolizidines

Abstract

Brightly colored ranid frogs of the genus Mantella are found only in rain forests of Madagascar. Gc-ms and gc-Ft-ir analyses of skin alkaloids of seven different species, including four populations of Mantella madagascariensis, are reported. All contain one or more representatives of the pumiliotoxin A (PTX-A) class with the 13,14-dihydro derivatives 309A and 325A found in major amounts in the four populations of M. madagascariensis, while 307A (PTX-A) is found in two populations of M. madagascariensis and in three additional species, Mantella aurantiaca, Mantella viridis, and Mantella crocea. The latter three species also contain appreciable quantities of 323A (PTX-B). The four populations of M. madagascariensis show major amounts of two 1,4-disubstituted quinolizidines, 217A and 231A, and a 5,8-disubstituted indolizidine, 217B, in addition to many minor or trace quinolizidines and indolizidines. Such disubstituted quinolizidines and indolizidines are present as trace alkaloids in the six other species of Mantella, along with 3,5-disubstituted indolizidines, 3,5-disubstituted pyrrolizidines, the decahydroquinoline cis-195A, tricyclic alkaloids, and homopumiliotoxins. A new alkaloid class, which appears to contain a quinolizidine moiety, is seen in M. aurantiaca and M. crocea and is represented by 235C and several congeners.

Convergent evolution of chemical defense in poison frogs and arthropod prey between Madagascar and the Neotropics

“…Poison frogs have been recognized in four families: South American Melanophyrniscus (Bufonidae); Australian Pseudophryne (Myobatrachidae); Central and South American Dendrobates, Epipedobates, and Phyllobates (Dendrobatidae); and Malagasy (Madagascan) Mantella (Mantellidae) (1,(4)(5)(6)(7)(8). Additionally, trace amounts of such alkaloids have been detected in a Thai ranid frog, Limnonectes kuhli (9).…”

“…More than 100 alkaloids of 12 classes have been detected in skin of Mantella (1,4,6,(39)(40), and many also occur in Neotropical poison frogs. In addition to their ability to sequester and accumulate alkaloids from diet, Mantella and some dendrobatid frogs also share the following features: terrestrial eggs, small body size (Ͻ50-mm snout-vent length), toothless jaws, a specialist diet composed largely of ants, active diurnal foraging behaviors, and aposematic coloration; all features are considered to have been produced by convergent evolution (4,(41)(42)(43)(44)(45).…”

Evidence for an enantioselective pumiliotoxin 7-hydroxylase in dendrobatid poison frogs of the genus Dendrobates

“…Many of the alkaloids, for example the batrachotoxins, the pumiliotoxins (PTXs) and allopumiliotoxins (aPTXs), and epibatidine, were highly toxic, whereas others, such as the decahydroquinolines (DHQs), the histrionicotoxins and the izidines, were of low toxicity, but would still serve as deterrents to predators because of bitter, unpleasant effects on buccal tissue (8,9). ''Dendrobatid alkaloids'' are now known to occur in one genus from each of three other anuran families, namely Mantella from the Madagascan family Mantellidae (10,11), the South American Melanophryniscus from the family Bufonidae (12) and the Australian Pseudophryne from the family Myobatrachidae (13). The Mantella frogs, like the dendrobatid frogs, seemed dependent on a dietary source (14).…”

Bioactive alkaloids of frog skin: Combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source

“…It now seems that all dendrobatid alkaloids are of dietary origin (8,9), which for such frogs consists of small, even tiny arthropods. Indeed, the common evolutionary event leading to skin alkaloids in dendrobatid frogs, Madagascan mantellid frogs (10), and South American bufonid toads (11) is probably the overexpression of an uptake system for sequestration of dietary alkaloids into skin glands. Australian myobatrachid frogs of the genus Pseudophryne synthesize their own unique indolic pseudophrynamines while sequestering pumiliotoxins (PTXs) from a dietary source (12).…”