Pumiliotoxin 251D

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ImageFile=Pumiliotoxin251D.pngImageSize=240
IUPACName=(8R,8aS)-8-methyl-6- [(2R)-2-methylhexylidene] -1,2,3,5,7,8a-hexahydroindolizine-8-ol
OtherNames=Pumiliotoxin 251D
Section1=Chembox Identifiers
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SMILES= C2C(O)(C)C1CCCN1CC2=CC(C)CCCC
Section2=Chembox Properties
C=16 | H=29 | N=1 | O=1
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Section3=Chembox Hazards
MainHazards=Toxic
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Pumiliotoxin 251D is one of the toxins found in the skin of poison frogs from the "Dendrobates", "Epipedobates", "Minyobates" and "Phyllobates" [Edwards MW, Daly JW, Myers CW. Alkaloids from a panamanian poison frog, Dendrobates speciosus: identification of pumiliotoxin-A and allopumiliotoxin class alkaloids, 3,5-disubstituted indolizidines, 5-substituted 8-methylindolizidines, and a 2-methyl-6-nonyl-4-hydroxypiperidine. "Journal of Natural Products". 1988 Nov-Dec;51(6):1188-97. PMID 3236011] [Mortari MR, Schwartz EN, Schwartz CA, Pires OR Jr, Santos MM, Bloch C Jr, Sebben A. Main alkaloids from the Brazilian dendrobatidae frog Epipedobates flavopictus: pumiliotoxin 251D, histrionicotoxin and decahydroquinolines. "Toxicon". 2004 Mar 1;43(3):303-10. PMID 15033329] and toads from the "Melanophryniscus" families. [Mebs D, Pogoda W, Maneyro R, Kwet A. Studies on the poisonous skin secretion of individual red bellied toads, Melanophryniscus montevidensis (Anura, Bufonidae), from Uruguay. "Toxicon". 2005 Nov;46(6):641-50. PMID 16157358] [Mebs D, Maneyro R, Pogoda W. Further studies on pumiliotoxin 251D and hydroquinone content of the skin secretion of Melanophryniscus species (Anura, Bufonidae) from Uruguay. "Toxicon". 2007 Jul;50(1):166-9. PMID 17433395] It is not manufactured by the amphibians, but absorbed through their insect-rich diet. [Saporito RA, Garraffo HM, Donnelly MA, Edwards AL, Longino JT, Daly JW. Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs. "Proceedings of the National Academy of Sciences USA". 2004 May 25;101(21):8045-50. PMID 15128938] [Takada W, Sakata T, Shimano S, Enami Y, Mori N, Nishida R, Kuwahara Y. Scheloribatid mites as the source of pumiliotoxins in dendrobatid frogs. "Journal of Chemical Ecology". 2005 Oct;31(10):2403-15. PMID 16195851] It is extremely toxic to mosquitoes. [Weldon PJ, Kramer M, Gordon S, Spande TF, Daly JW. A common pumiliotoxin from poison frogs exhibits enantioselective toxicity against mosquitoes. "Proceedings of the National Academy of Sciences USA". 2006 Nov 21;103(47):17818-21. PMID 17095598]

Pumiliotoxin 251D is a powerful toxin with several mechanisms of action, both blocking sodium and potassium channels in cells, [Vandendriessche T, Abdel-Mottaleb Y, Maertens C, Cuypers E, Sudau A, Nubbemeyer U, Mebs D, Tytgat J. Modulation of voltage-gated Na+ and K+ channels by pumiliotoxin 251D: a "joint venture" alkaloid from arthropods and amphibians. "Toxicon". 2008 Mar 1;51(3):334-44. PMID 18061227] and inhibiting calcium-dependent ATPase. [Tamburini R, Albuquerque EX, Daly JW, Kauffman FC. Inhibition of calcium-dependent ATPase from sarcoplasmic reticulum by a new class of indolizidine alkaloids, pumiliotoxins A, B, and 251D. "Journal of Neurochemistry". 1981 Sep;37(3):775-80. PMID 6456330] [Daly JW, McNeal ET, Overman LE, Ellison DH. A new class of cardiotonic agents: structure-activity correlations for natural and synthetic analogues of the alkaloid A new class of A new class of cardiotonic agents: structure-activity correlations for natural and synthetic analogues of the alkaloid pumiliotoxin B (8-hydroxy-8-methyl-6-alkylidene-1-azabicyclo [4.3.0] nonanes). "Journal of Medicinal Chemistry". 1985 Apr;28(4):482-6. PMID 3981541]

Some poison frogs have the ability to convert pumiliotoxin 251D into allopumiliotoxin 267A, a more potent variant of the toxin. [Daly JW, Garraffo HM, Spande TF, Clark VC, Ma J, Ziffer H, Cover JF Jr. Evidence for an enantioselective pumiliotoxin 7-hydroxylase in dendrobatid poison frogs of the genus Dendrobates. "Proceedings of the National Academy of Sciences USA". 2003 Sep 16;100(19):11092-7. PMID 12960405]

References