[en] Arrow and dart poisons, considered as conventional natural sources for future drug discovery, have already provided numerous biologically active molecules used as drugs in therapeutic applications or in pharmacological research. Plants containing alkaloids or cardiotonic glycosides have generally been the main ingredients responsible for the efficacy of these poisons, although some animals, such as frogs, have also been employed. This paper, without being exhaustive, reports the greater strides made during the past 15 years in the understanding of the chemical nature and biological properties of arrow and dart poison constituents. Examples both of promising biological properties shown by these molecules and of crucial discoveries achieved by their use as pharmacological tools are given. Further studies of these toxic principles are likely to enable scientists to find new valuable lead compounds, useful in many fields of research, like oncology, inflammation and infectious diseases. 2005 Elsevier Ireland Ltd. All rights reserved.
Akimova, O.A., Bagrov, A.Y., Lopina, O.D., Kamernitsky, A.V., Tremblay, J., Hamet, P., Orlov, S.N., Cardiotonic steroids differentially affect intracellular Na+ and [Na+](i)/[K+](i)-independent signaling in C7-MDCK cells (2005) Journal of Biological Chemistry, 280, pp. 832-839
Alencar, N.M.N., Figueiredo, I.S.T., Vale, M.R., Bitencurt, F.S., Oliveira, J.S., Ribiro, R.A., Ramos, M.V., Anti-inflammatory effect of the latex from Calotropis procera in three different experimental models: Peritonitis, paw edema and hemorrhagic cystitis (2004) Planta Medica, 70, pp. 1144-1149
Anand, C.H., Stimson, W.H., Gray, A.I., (2002), Pharmaceutical composition containing uscharidin or its analogues. US Patent 6342490
Baraznenok, I.L., Jonsson, E., Claesson, A., 3-(2,5-Dihydro-1H-pyrrol-2-ylmethoxy)pyridines: Synthesis and analgesic activity (2005) Bioorganic & Medicinal Chemistry Letters, 15, pp. 1637-1640
Bereta, J., Cohen, M.C., Bereta, M., Stimulatory effect of ouabain on VCAM-1 and iNOS expression in murine endothelial cells: Involvement of NF-kappa B (1995) FEBS Letters, 377, pp. 21-25
Bisset, N.G., Arrow and dart poisons (1989) Journal of Ethnopharmacology, 25, pp. 1-41
Bisset, N.G., Curare (1992) Alkaloids: Chemical and Biological Perspectives, 8. , W.S. Pelletier Springer Berlin
Bisset, N.G., War and hunting poisons of the New World. Part 1. Notes on the early history of curare (1992) Journal of Ethnopharmacology, 36, pp. 1-26
Brüschweiler, F., Stöcklin, W., Stöckel, K., Reichstein, T., Die glykoside von Calotropis procera R.Br (1969) Helvetica Chimica Acta, 52, pp. 2086-2106
Cai, B., Nagasawa, T., Kadota, S., Hattori, M., Namba, T., Kuraishi, Y., Processing of Nux Vomica. VII. Antinociceptive effects of crude alkaloids from the processed and unprocessed seeds of Strychnos nux vomica in mice (1996) Biological and Pharmaceutical Bulletin, 19, pp. 127-131
Carter, C.A., Forney, R.W., Gray, E.A., Gehring, A.M., Schneider, T.L., Young, D.B., Lovett Jr., C.M., Richardson, D.P., Toxicarioside A. a new cardenolide isolated from Antiaris toxicaria latex-derived dart poison. Assignment of the 1H- and 13C-NMR shifts for an antiarigenin aglycon (1997) Tetrahedron, 53, pp. 13557-13566
Carter, C.A., Gray, E.A., Schneider, T.L., Lovett Jr., C.M., Scott, L., Messer, A.C., Richardson, D.P., Toxicarioside B and toxicarioside C, new cardenolides isolated from Antiaris toxicaria latex-derived dart poison (1997) Tetrahedron, 53, pp. 16959-16968
Cheung, H.T.A., Chiu, F.C.K., Watson, T.R., Wells, R.S., Cardenolides glycosides of the Asclepiadaceae. New glycosides from Asclepias fructicosa and the stereochemistry of uscharin, voruscharin, and calotoxin (1983) Journal of the Chemical Society, Perkin Transactions, 1, pp. 2827-2835
Daly, J.W., Secunda, S.I., Garraffo, H.M., Spande, T.F., Wisnieski, A., Cover, J.F., An uptake system for dietary alkaloids in poison frogs (Dendrobatidae) (1994) Toxicon, 32, pp. 657-663
Daly, J.W., Thirty years of discovering arthropod alkaloids in amphibian skin (1998) Journal of Natural Products, 61, pp. 162-172
Dmitrieva, R.I., Doris, P.A., Cardiotonic steroids, potential endogenous sodium pump ligands with diverse function (2002) Experimental Biology and Medicine, 227, pp. 561-569
Dmitrieva, R.I., Doris, P.A., Ouabain is a potent promoter of growth and activator of ERK1/2 in ouabain-resistant rat renal epithelial cells (2003) Journal of Biological Chemistry, 278, pp. 28160-28166
Dumbacher, J.P., Beehler, B.M., Spande, T.F., Garraffo, H.M., Daly, J.W., Homobatrachotoxin in the genus Pitohui: Chemical defense in birds? (1992) Science, 258, pp. 799-801
Dumbacher, J.P., Wako, A., Derrickson, S.R., Samuelson, A., Spande, T.F., Daly, J.W., Melyrid beetles (Choresine): A putative source for the batrachotoxin alkaloids found in poison-dart frogs and toxic passerine birds (2004) Proceedings of the National Academy of Sciences of the United States of America, 101, pp. 15857-15860
Frédérich, M., De Pauw, M.-C., Prosperi, C., Tits, M., Brandt, V., Penelle, J., Hayette, M.-P., Angenot, L., Strychnogucines a and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja (2001) Journal of Natural Products, 64, pp. 12-16
Frédérich, M., Jacquier, M.J., Thépenier, P., De Mol, P., Tits, M., Philippe, G., Delaude, C., Zèches-Hanrot, M., Antiplasmodial activity of alkaloids from various Strychnos species (2002) Journal of Natural Products, 65, pp. 1381-1386
Frédérich, M., Bentires-Alj, M., Tits, M., Angenot, L., Greimers, R., Gielen, J., Bours, V., Merville, M.P., Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, induces cell cycle arrest and apoptosis in human colon cancer cells (2003) Journal of Pharmacology and Experimental Therapeutics, 304, pp. 1103-1110
Frédérich, M., Tits, M., Goffin, E., Philippe, G., Grellier, P., De Mol, P., Hayette, M.-P., Angenot, L., In vitro and in vivo antimalarial properties of isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis (2004) Planta Medica, 70, pp. 520-525
Gerzanich, V., Peng, X., Wang, F., Wells, G., Anand, R., Fletcher, S., Lindstrom, J., Comparative pharmacology of epibatidine - A potent agonist for neuronal nicotinic acetylcholine-receptors (1995) Molecular Pharmacology, 48, pp. 774-782
Gotti, C., Clementi, F., Neuronal nicotinic receptors: From structure to pathology (2004) Progress in Neurobiology, 74, pp. 363-396
Haux, J., Digitoxin is a potential anticancer agent for several types of cancer (1999) Medical Hypotheses, 53, pp. 543-548
Haux, J., Klepp, O., Spigset, O., Tretli, S., Digitoxin medication and cancer
Case control and internal dose-response studies (2001) BMC Cancer, 1, p. 11
Haux, J., Digitalis
Impinges on more than just the (ion-) pump (2002) Medical Hypotheses, 59, pp. 781-782
Huang, Y.T., Chueh, S.C., Teng, C.M., Guh, J.H., Investigation of ouabain-induced anticancer effect in human androgen-independent prostate cancer PC-3 cells (2004) Biochemical Pharmacology, 67, pp. 727-733
Koehn, F.E., Carter, G.T., The evolving role of natural products in drug discovery (2005) Nature Reviews Drug Discovery, 4, pp. 206-220
Kometiani, P., Liu, L.J., Askari, A., Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells (2005) Molecular Pharmacology, 67, pp. 929-936
Kopp, B., Bauer, W.P., Bernkop-Schnürch, A., Analysis of some Malaysian dart poisons (1991) Journal of Ethnopharmacology, 36, pp. 57-62
Kumar, V.L., Basu, N., Anti-inflammatory activity of the latex of Calotropis procera (1994) Journal of Ethnopharmacology, 44, pp. 123-125
Li, S., Gosling, M., Poll, C.T., Westwick, J., Cox, B., Therapeutic scope of modulation of non-voltage-gated cation channels (2005) Drug Discovery Today, 10, pp. 129-137
Manna, S.K., Sah, N.K., Newman, R.A., Cisneros, A., Aggarwal, B.B., Oleandrin suppresses activation of nuclear transcription factor-κB, activator protein-1, and c-Jun NH2-terminal kinase (2000) Cancer Research, 60, pp. 3838-3847
Masocha, W., Horvath, G., Agil, A., Ocana, M., Del Pozo, E., Szikszay, M., Baeyens, J.M., Role of Na+, K+-ATPase in morphine-induced antinociception (2003) Journal of Pharmacology and Experimental Therapeutics, 306, pp. 1122-1128
Neuwinger, H.D., (1996) African Ethnobotany. Poisons and Drugs. Chemistry, Pharmacology, Toxicology, , Chapman & Hall London
Newman, D.J., Cragg, G.M., Snader, K.M., Natural products as sources of new drugs over the period 1981-2002 (2003) Journal of Natural Products, 66, pp. 1022-1037
Patocka, J., Ardilla, M.S., Vasquez, M.V., Dendrobatidae frog poisons-inspiration for bioorganic chemistry (2000) Chemicke Listy, 94, pp. 230-233
Penelle, J., Christen, P., Molgo, J., Tits, M., Brandt, V., Frederich, M., Angenot, L., 5′,6′-Dehydroguiachrysine and 5′,6′- dehydroguiaflavine, two curarizing quaternary indole alkaloids from the stem bark of Strychnos guianensis (2001) Phytochemistry, 58, pp. 619-626
Philippe, G., Prost, E., Nuzillard, J.-M., Zèches-Hanrot, M., Tits, M., Angenot, L., Frédérich, M., Strychnohexamine from Strychnos icaja, a naturally occuring trimeric indolomonoterpenic alkaloid (2002) Tetrahedron Letters, 43, pp. 3387-3390
Philippe, G., Angenot, L., Tits, M., Frédérich, M., About the toxicity of some Strychnos species and their alkaloids (2004) Toxicon, 44, pp. 405-416
Phillipson, J.D., A matter of some sensitivity (1995) Phytochemistry, 38, pp. 1319-1343
Qian, C.G., Li, T.C., Shen, T.Y., Libertine-Garahan, L., Eckman, J., Biftu, T., Ip, S., Epibatidine is a nicotinic analgesic (1993) European Journal of Pharmacology, 250, pp. 13-R14
Rajendra, S., Lynch, J.W., Schofield, P.R., The glycine receptor (1997) Pharmacology and Therapeutics, 73, pp. 121-146
Sagen, A.-L., Gertsch, J., Becker, R., Heilmann, J., Sticher, O., Quinolizidine alkaloids from the curare adjuvant Clathrotropis glaucophylla (2002) Phytochemistry, 61, pp. 975-978
Schneider, G., Wolfling, J., Synthetic cardenolides and related compounds (2004) Current Organic Chemistry, 8, pp. 1381-1403
Schwinger, R.H.G., Bundgaard, H., Müller-Ehmsen, J., Kjeldsen, K., The Na, K-ATPase in the failing human heart (2003) Cardiovascular Research, 57, pp. 913-920
Senanayake, N., Roman, G.C., Disorders of neuromuscular transmission due to natural environmental toxins (1992) Journal of Neurological Sciences, 107, pp. 1-13
Shrestha, T., Kopp, B., Bisset, N.G., The Moraceae-based dart poisons of South America. Cardiac glycosides of Maquira and Naucleopsis species (1992) Journal of Ethnopharmacology, 37, pp. 129-143
Smit, H.F., Woerdenbag, H.J., Singh, R.H., Meulenbeld, G.J., Labadie, R.P., Zwaving, J.H., Ayurvedic herbal drugs with possible cytostatic activity (1995) Journal of Ethnopharmacology, 47, pp. 75-84
Smith, S.Q., Jones, T.H., Tracking the cryptic pumiliotoxins (2004) Proceedings of the National Academy of Sciences of the United States of America, 101, pp. 7841-7842
Soares, P.M., Lima, S.R., Matos, S.G., Andrade, M.M., Patrocinio, M.C.A., De Freitas, C.D.T., Ramos, M.V., Vasconcelos, S.M.M., Antinociceptive activity of Calotropis procera latex in mice (2005) Journal of Ethnopharmacology, 99, pp. 125-129
Spande, T.F., Garraffo, H.M., Edwards, M.W., Yeh, H.J.C., Pannell, L., Daly, J.W., Epibatidine - A novel (chloropyridyl)azabicycloheptane with potent analgesic activity from an Ecuadorian poison frog (1992) Journal of the American Chemical Society, 114, pp. 3475-3478
Srivastava, M., Eidelman, O., Zhang, J., Paweletz, C., Caohuy, H., Yang, Q.F., Jacobson, K.A., Pollard, H.B., Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells (2004) Proceedings of the National Academy of Sciences of the United States of America, 101, pp. 7693-7698
Tulp, M., Bohlin, L., Unconventional natural sources for future drug discovery (2004) Drug Discovery Today, 9, pp. 450-458
Van Quaquebeke, E., Darro, F., Kiss, R., Dewelle, J., Simon, G., Braekman, J.-C., Nacoulma, O.G., Guissou, P., (2004), EP Patent 1408043. 2″-Oxovoruscharin and analogues thereof
Van Quaquebeke, E., Simon, G., André, A., Dewelle, J., El Yazidi, M., Bruyneel, F., Tuti, J., Darro, F., Identification of a novel cardenolide (2″-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: Structure-activity relationship analyses (2005) Journal of Medicinal Chemistry, 48, pp. 849-856
Wei, Z.L., Xiao, Y., Kellar, K.J., Kozikowski, A.P., Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors (2004) Bioorganic & Medicinal Chemistry Letters, 14, pp. 1855-1858
Wins, P., Margineanu, I., Penelle, J., Angenot, L., Grisar, T., Bettendorff, L., Bisindole alkaloids from Strychnos guianensis are effective antagonists of nicotinic acetylcholine receptors in cultured human TE671 cells (2003) Naunyn-Schmiedeberg's Archives of Pharmacology, 367, pp. 253-259
Xie, Z.J., Ouabain interaction with cardiac Na/K-ATPase reveals that the enzyme can act as a pump and as a signal transducer (2001) Cellular and Molecular Biology, 47, pp. 383-390
