Journal of Chemical Ecology

, Volume 26, Issue 6, pp 1477–1496 | Cite as

Structure–Activity Relationship of Inhibition of Fish Feeding by Sponge-derived and Synthetic Pyrrole–Imidazole Alkaloids

  • Thomas Lindel
  • Holger Hoffmann
  • Matthias Hochgürtel
  • Joseph R. Pawlik


We investigated the relationship between the structures of pyrrole-containing alkaloids from marine sponges of the genus Agelas and their capacity to deter feeding by the omnivorous Caribbean reef fish, Thalassoma bifasciatum. Seven natural products were assayed at volumetric concentrations of 1, 5, and 10 mg/ml: dispacamide A, keramadine, oroidin, midpacamide, 4,5-dibromopyrrole-2-carboxylic acid, 4,5-dibromopyrrole-2carboxamide, and racemic longamide A. We also assayed 14 structural analogs obtained mostly by chemical synthesis. Of the seven natural products, only rac-longamide A was not significantly deterrent at any of the assay concentrations. The pyrrole moiety was required for feeding inhibition activity, while the addition of the imidazole group enhanced this activity. Variously functionalized imidazoles lacking the pyrrole moiety were not deterrent. Combinations of the natural products appeared to have an additive effect on feeding inhibition; there was no evidence of synergy. Given their high concentrations in sponge tissue, dispacamide A and oroidin most probably serve as the primary chemical defenses of many Agelas sp., while minor compounds such as keramadine are not present in high enough concentrations to contribute much to chemical defense.

Chemical defense sponges predation Agelas pyrrole–imidazole alkaloids structure–activity relationship synthesis 


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  1. Assmann, M., Lichte, E., Pawlik, J. R., and KÖck, M. 2000. Chemical defenses of the Caribbean sponges Agelas wiednemayeri and Agelas conifera. Submitted to Mar. Ecol. Prog. Ser. Google Scholar
  2. Bailey, D. M., and Johnson, R. E. 1973. Pyrrole antibacterial agents. 2. 4,5-Dihalopyrrole-2-carboxylic acid derivatives. J. Med. Chem. 16:1300–1302.Google Scholar
  3. Braekman, J. C., Daloze, D., Moussiaux, B., Stoller, C., and Deneubourg, F. 1989. Sponge secondary metabolites: new results. Pure Appl. Chem. 61:509–512.Google Scholar
  4. Cafieri, F., Fattorusso, E., Mangoni, A., and Taglialatela-Scafati, O. 1995. Longamide and 3,7-dimethylisoguanine, two novel alkaloids from the marine sponge Agelas longissima. Tetrahedron Lett. 36:7893–7896.Google Scholar
  5. Cafieri, F., Fattorusso, E., Mangoni, A., and Taglialatela-Scafati, O. 1996. Dispacamides, anti-histamine alkaloids from Caribbean Agelas sponges. Tetrahedron Lett. 37:3587–3590.Google Scholar
  6. Cafieri, F., Carnuccio, R., Fattorusso, E., Taglialatela-Scafati, O., and Vallefuoco, T. 1997. Anti-histaminic activity of bromopyrrole alkaloids isolated from Caribbean Agelas spones. Bioorg. Med. Chem. Lett. 7:2283–2288.Google Scholar
  7. Cafieri, F., Fattorusso, E., and Taglialatela-Scafati, O. 1998. Novel bromopyrrole alkaloids from the sponge Agelas dispar. J. Nat. Prod. 61:122–125.Google Scholar
  8. Chanas, B., and Pawlik, J. R. 1995. Defenses of Caribbean sponges against predatory reef fish. II. Spicules, tissue toughness, and nutritional quality. Mar. Ecol. Prog. Ser. 127:195–211.Google Scholar
  9. Chanas, B., Pawlik, J. R., Lindel, T., and Fenical, W. 1996. Chemical defense of the Caribbean sponge Agelas clathrodes. J. Exp. Mar. Biol. Ecol. 208:185–196.Google Scholar
  10. Chevolot, L., Padua, S., Ravi, B. N., Blyth, P. C., and Scheuer, P. J. 1977. Isolation of 1-methyl-4,5-dibromopyrrole-2-carboxylic acid and its 3′-(hydantoyl)propylamide (midpacamide) from a marine sponge. Heterocycles 7:891–894.Google Scholar
  11. De Nanteuil, G., Ahond, A., Guilhem, J., Poupat, C., Trans Huu Dau, E., Potier, P., Pusset, M., Pusset, J., and Laboute, P. 1985. Isolement et identification des metabolites d'une nouvelle espece de spongaire, Pseudaxinyssa cantharella. Tetrahedron 41:6019–6033.Google Scholar
  12. Duffy, J. E., and Paul, V. J. 1992. Prey nutritional quality and the effectiveness of chemical defenses against tropical reef fishes. Oecologia 90:333–339.Google Scholar
  13. Enriz, R. D., Baldoni, H. A., Jauregui, E. A., Sosa, M. E., Tonn, C. E., and Giordano, O. S. 1994. Structure-activity relationship of clerodane diterpenoids acting as antifeeding agents. J. Agric. Food Chem. 42:2958–2963.Google Scholar
  14. Fathi-Afshar, R., and Allen, T. M. 1988. Biologically active metabolites from Agelas mauritiana. Can. J. Chem. 66:45–50.Google Scholar
  15. Faulkner, D. J. 1998. Marine natural products. Nat. Prod. Rep. 15:113–158.Google Scholar
  16. Forenza, S., Minale, L., and Riccio, R. 1971. New bromopyrrole derivatives from the sponge Agelas oroides. J. Chem. Soc. Chem. Commun. 1971:1129–1130.Google Scholar
  17. Gonzalez-Coloma, A., Guadano, A., Gutierrez, C., Cabrera, R., De La PeÑa, E., De La Fuente, G., and Reina, M. 1998. Antifeedant delphinium diterpenoid alkaloids. Structure-activity relationships. J. Agric. Food Chem. 46:286–290.Google Scholar
  18. Gunasekera, S. P., Cranick, S., and Longley, R. E. 1989. Immunosuppressive compounds from a deep water marine sponge, Agelas flabelliformis. J. Nat. Prod. 52:757–761.Google Scholar
  19. Hay, M. E., Piel, J., Boland, W., and Schnitzler, I. 1998. Seaweed sex pheromones and their degradation products frequently suppress amphipod feeding but rarely suppress sea urchin feeding. Chemoecology 8:91–98.Google Scholar
  20. Hixon, M. A. 1983. Fish grazing and community structure of coral reefs and algae: A synthesis of recent studies, pp. 79–87, in M. S. Reaka (ed.). The Ecology of Deep and Shallow Coral Reefs. Symposia series for undersea research, NOAA /NURP, Washington, DC.Google Scholar
  21. JimÉnez, C., and Crews, P. 1994. Mauritamide A and accompanying oroidin alkaloids from the sponge Agelas mauritiana. Tetrahedron Lett. 35:1375–1378.Google Scholar
  22. KÖnig, G. M., Wright, A. D., and Linden, A. 1998. Antiplasmodial and cytotoxic metabolites from the maltese sponge Agelas oroides. Planta Med. 64:443–447.Google Scholar
  23. Lindel, T., and HochgÜrtel, M. 1998. The alkyne pathway to keramadine from the marine sponge Agelas sp. Tetrahedron Lett. 39:2541–2544.Google Scholar
  24. Lindel, T., and Hoffmann, H. 1997a. Synthesis of dispacamide from the maine sponge Agelas dispar. Tetrahedron Lett. 38:8935–8938.Google Scholar
  25. Lindel, T., and Hoffmann, H. 1997b. Synthesis of rac-midpacamide and the spiro-cyclization of its precursor. Liebigs Ann. Recueil 1997:1525–1528.Google Scholar
  26. Lindel, T., Junker, J., and KÖck, M. 1999. 2D-NMR-guided constitutional analysis of organic compounds employing the computer program COCON. Eur. J. Org. Chem. 1999:573–577.Google Scholar
  27. Mancini, I., Guella, G., Amade, P., Roussakis, C., and Pietra, F. 1997. Hanishin, a semiracemic, bioactive C9 alkaloid of the axinellid sponge Acanthella carteri from the Hanish Islands. A shunt metabolite? Tetrahedron Lett. 38:6271–6274.Google Scholar
  28. Meanwell, N. A., Roth, H. R., Smith, E. C. R., Wedding, D. L., and Wright, J. J. K. 1991. Diethyl 2,4-dioxoimidazoline-5-phosphonates: Horner-Wadsworth-Emmons reagents for the mild and efficient preparation of C-5 unsaturated hydantoin derivatives. J. Org. Chem. 56:6897–6904.Google Scholar
  29. Messchendorp, L., Gols, G. J. Z., and Van Loon, J. J. A. 1998. Behavioral effects and sensory detection of drimane deterrents in Myzus persicae and aphis gossypii nymphs. J. Chem. Ecol. 24:1433–1446.Google Scholar
  30. Moe, O. A., and Warner, D. T. 1949. 1,4 Addition reactions. III. The addition of cyclic imides to α,β-unsaturated aldehydes. A synthesis of β-alanine hydrochloride. J. Am. Chem. Soc. 71:1251–1253.Google Scholar
  31. Mullin, C. A., Gonzalez-Coloma, A., Gutierrez, C., Reina, M., Eichenseer, H., Hollister, B., and Chyb, S. 1997. Antifeedant effects of some novel terpenoids on chrysomelidae beetles: Comparisons with alkaloids on an alkaloid-adapted an nonadapted species. J. Chem. Ecol. 23:1851–1866.Google Scholar
  32. Nakamura, H., Ohizumi, Y., Kobayashi, J., and Hirata, Y. 1984. Keramadine, a novel antagonist of serotonergic receptors isolated from the Okinawan sea sponge Agelas sp. Tetrahedron Lett. 25:2475–2478.Google Scholar
  33. Pawlik, J. R. 1993. Marine invertebrate chemical defenses. Chem. Rev. 93:1911–1922.Google Scholar
  34. Pawlik, J. R., and Fenical, W. 1992. Chemical defense of Pterogorgia anceps, a Caribbean gorgonian coral. Mar. Ecol. Prog. Ser. 87:183–188.Google Scholar
  35. Pawlik, J. R., Burch, M. T., and Fenical, W. 1987. Patterns of chemical defense among Caribbean gorgonian corals: A preliminary survey. J. Exp. Mar. Biol. Ecol. 108:55–66.Google Scholar
  36. Pawlik, J. R., Chanas, B., Toonen, R. J., and Fenical, W. 1995. Defenses of Caribbean sponges against predatory reef fish. I. Chemical deterrency. Mar. Ecol. Prog. Ser. 127:183–194.Google Scholar
  37. Pennings, S. C., Pablo, S. R., Paul, V. J., and Duffy, E. 1994. Effects of sponge secondary metabolites in different diets on feeding by three groups of consumers. J. Exp. Mar. Biol. Ecol. 180:137–149.Google Scholar
  38. Randall, J. R., and Hartman, W. D. 1968. Sponge-feeding fishes of the West Indies. Mar. Biol. 1:216–225.Google Scholar
  39. Rogers, S. D., and Paul, V. J. 1991. Chemical defenses of three Glossodoris nudibranchs and their dietary Hyrtios sponges. Mar. Ecol. Prog. Ser. 77:221–232.Google Scholar
  40. Rowan, D. D., Hunt, M. B., and Gaynor, D. L. 1986. Peramine, a novel insect feeding deterrent from ryegrass infected with the endophyte Acromonium lolii. J. Chem. Soc. Chem. Commun. 1986:935–936.Google Scholar
  41. Tsukamoto, S., Kato, H., Hirota, H., and Fusetani, N. 1996. Ceratinamides A and B: New antifouling dibromotyrosine derivatives from the marine sponge Pseudoceratina purpurea. Tetrahedron 52:8181–8186.Google Scholar
  42. Umeyana, A., Ito, S., Yuasa, E., Arihara, S., and Yamada, T. 1998. A new bromopyrrole alkaloid and the optical resolution of the racemate from the marine sponge Homaxinella sp. J. Nat. Prod. 61:1433–1434.Google Scholar
  43. Vervoort, H. C., Pawlik, J. R., and Fenical, W. 1998. Chemical defense of the Caribbean ascidian Didemnum conchyliatum. Mar. Ecol. Prog. Ser. 164:221–228.Google Scholar
  44. Walker, R. P., Faulkner, D. J., Van Engen, D., and Clardy, J. 1981. Sceptrin, an antimicrobial agent from the sponge Agelas sceptrum. J. Am. Chem. Soc. 103:6772–6773.Google Scholar
  45. Wilson, D. M., Puyana, M., Fenical, W., and Pawlik, J. R. 1999. Chemical defense of the Caribbean reef sponge Axinella corrugata against predatory fishes. J. Chem. Ecol. 25:2811–2823.Google Scholar
  46. Yamazaki, T., Benedetti, E., Kent, D., and Goodman, M. 1994. Konformationsvoraussetzungen für den süssen Geschmack von Dipeptiden und Dipeptidmimetica. Angew. Chem. 106:1502–1517.Google Scholar
  47. Zar, J. H. 1984. Biostatistical Analysis, 2nd ed. Prentice-Hall, Englewood Cliffs, New Jersey.Google Scholar

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Thomas Lindel
    • 1
  • Holger Hoffmann
    • 1
  • Matthias Hochgürtel
    • 1
  • Joseph R. Pawlik
    • 2
  1. 1.Pharmazeutisch-chemisches InstitutUniversität HeidelbergHeidelbergGermany
  2. 2.Biological Sciences and Center for Marine ScienceUniversity of North Carolina at WilmingtonWilmington

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