The Precocene Antijuvenile Hormones (Allatotoxins): A Case History in Insect Toxicology

  • G. T. Brooks
  • A. R. McCaffery
Part of the Chromatographic Society Symposium Series book series (CSSS)


The precocenes (ageratochromenes) have attracted attention as the first examples of simple molecules, superficially dissimilar in structure to the natural juvenile hormones (JHs) yet able to elicit remarkable JH-antagonistic effects in some species of insects. Precocenes appear to exert a cytotoxic action on the corpora allata (CA), mediated by an oxidative bioactivation in vivo. Reactive epoxide formation in the CA is the mechanism that currently best explains the results of several radiochromatographically based metabolism studies in precocene-sensitive insects. Other oxidatively derived reactive intermediates such as quinone-methides or oxyradicals have been suggested but these mechanisms await substantiation. The limited pharmacokinetic studies on precocenes conducted so far have not revealed differences that convincingly explain their species selectivity but methods must be found to maintain the bioavailability of parent precocenes to the CA for longer periods, especially in the seemingly insensitive larvae of lepidoptera.


Juvenile Hormone Corpus Allata Corpus Allata Piperonyl Butoxide Diethyl Maleate 


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  1. 1.
    W. S. Bowers, T. Ohta, J. S. Cleere and P. A. Marsella, Discovery of insect anti-juvenile hormones in plants, Science, 193:542–547 (1976).PubMedCrossRefGoogle Scholar
  2. 2.
    T. Ohta, R. J. Kuhr and W. S. Bowers, Radiosynthesis and metabolism of the insect anti-juvenile hormone, precocene-II, J. Agricul. Food Chem, 25:478–481 (1977).CrossRefGoogle Scholar
  3. 3.
    G. T. Brooks, Epoxide hydratase as a modifier of biotransformation and biological activity, Gen. Pharmacol, 8:221–226 (1977).PubMedCrossRefGoogle Scholar
  4. 4.
    G. E. Pratt and W. S. Bowers, Precocene-II inhibits juvenile hormone biosynthesis by cockroach corpora allata in vitro, Nature, 265:548–550 (1977).CrossRefGoogle Scholar
  5. 5.
    W. S. Bowers, Anti-juvenile hormones from plants: chemistry and biological activity, Ponttficiae Academiae Scientiarum Scripta Varia, 41:129–156 (1977).Google Scholar
  6. 6.
    G. T. Brooks, G. E. Pratt and R C. Jennings, The action of precocenes in milkweed bugs (Oncopeltusfasciatus) and locusts (Locustamigratoria), Nature, 281:570–572 (1979).CrossRefGoogle Scholar
  7. 7.
    G. T. Brooks, A F. Hamnett, R C. Jennings, A. P. Ottridge and G. E. Pratt, Aspects of the mode of action of precocenes on milkweed bugs (O.fasciatus) and locusts (L. migratoria), Proceedings of the 1979 British Crop Protection Conference — Pests and Diseases, 1:273–279(1979).Google Scholar
  8. 8.
    M. E. Burt, R. J. Kuhr and W. S. Bowers, Metabolism of precocene-II in the cabbage looper and European corn borer,Pest. Biochem. Physiol., 9:300–303 (1978).CrossRefGoogle Scholar
  9. 9.
    D. M. Soderlund, A. Messeguer and W. S. Bowers, Precocene-II metabolism in insects: synthesis of potential metabolites and identification of initial in vitro biotrans formation products, J. Agricul. Food Chem., 28:724–731 (1980).CrossRefGoogle Scholar
  10. 10.
    G. E. Pratt, R. C. Jennings and A. F. Hamnett, The mode of action of precocenes, Scientific Papers of the Institute of Organic and Physical Chemistry of Wroclaw Technical University, No. 22, Part 1:347–356 (1981).Google Scholar
  11. 11.
    G. E. Pratt, R. C. Jennings, A. F. Hamnett and G. T. Brooks, Lethal metabolism of precocene-I to a reactive epoxide by locust corpora allata, Nature, 284:320–323 (1980).CrossRefGoogle Scholar
  12. 12.
    B. J. Bergot, K. J. Judy, D. A. Schooley and L. W. Tsai, Precocene-II metabolism: comparative in vivo studies among several species of insects, and structure elucidation of two major metabolites,Pest. Biochem. Physiol., 13:95–104 (1980).CrossRefGoogle Scholar
  13. 13.
    R. C. Jennings, Synthesis, resolution and absolute configuration of the diol metabolites of precocene-I, Tetrahedron Letters, 23:2693–2696 (1982).CrossRefGoogle Scholar
  14. 14.
    A. F. Hamnett and G. E. Pratt, The absolute configuration of precocene-I dihydrodiols produced by metabolism of precocene-I by corpora allata of Locusta migratoria in vitro. Life Sciences, 32:2747–2753 (1983).PubMedCrossRefGoogle Scholar
  15. 15.
    A. R. McCaffery and P. G. McDowell, Titres of precocene-I and its metabolites in the haemolymph of larvae of the African armyworm Spodoptera exempta following topical treatment with the compound,Pest. Sci. 19:185–196 (1987).CrossRefGoogle Scholar
  16. 16.
    H. Aizawa, W. S. Bowers and D. M. Soderlund, Reactions of precocene-II epoxide with model nucelophiles, J. Agricul. Food Chem., 33:406–411 (1985).CrossRefGoogle Scholar
  17. 17.
    F. Camps, A. Conchillo and A. Messeguer, 3,4-Epoxyprecocene as a model of cytotoxic epoxides: synthesis of trans adducts occuring in the glutathione metabolic pathway, Tetrahedron, 43:3067–3074 (1987).CrossRefGoogle Scholar
  18. 18.
    D. M. Soderlund, M. F. Feldlaufer, S. Y. Takahashi and W. S. Bowers, Mechanisms of selectivity in the action of precocenes, in: “Juvenile Hormone Biochemistry”, G. E. Pratt and G. T. Brooks, eds., Elsevier/North Holland, Amsterdam, pp 353–362 (1981).Google Scholar
  19. 19.
    R. C. Jennings and A. P. Ottridge, The synthesis of precocene-I epoxide, J. Chem. Soc. Chem Comm., 920–921 (1979).Google Scholar
  20. 20.
    A. F. Hamnett, A. P. Ottridge, G. E. Pratt, R. C. Jennings and K. M. Stott, Kinetics and products of the hydrolysis of 3,4-dihydroprecocene-I-epoxide in aqueous organic solvents,Pest. Sci. 12:245–254 (1981).CrossRefGoogle Scholar
  21. 21.
    N. H. Haunerland and W. S. Bowers, Comparative studies on pharmacokinetics and metabolism of the anti-juvenile hormone precocene-II, Archives Insect Biochem. Physiol., 2:55–63 (1985).CrossRefGoogle Scholar
  22. 22.
    G. T. Brooks, A. P. Ottridge, R. C. Jennings, D. W. Mace and B. A. J. Alexander, The effect of 2,2-dimethylchromene derivatives and some other compounds on the development of O. fasciatus (Dallas) and Locusta migratoria (R&F),Pest. Sci. 16:571–588 (1985).CrossRefGoogle Scholar
  23. 23.
    X. Belles, M. Baldellou and A. Messeguer, Synergistic action of diethyl maleate on the morphogenetic and antigonadotropic activity of precocenes on the seed bug Oxycarenus lavaterae (F.), Archives Insect Biochem. Physiol., 4:107–112 (1987).CrossRefGoogle Scholar
  24. 24.
    X. Belles, F. Camps, J. Casas, A. Messeguer and M. D. Piulachs, In vitro inhibition of juvenile hormone III biosynthesis by precocene-II and 3,4-dihydroprecocene-II on Blattella germanica, J. Insect Physiol., 34:457–461 (1988).CrossRefGoogle Scholar
  25. 25.
    S. Orrenius, H. Thor, D. Dimonte, G. Bellomo, P. Nicotera, D. Ross and M. T. Smith, Mechanisms of oxidative cell injury studied in intact cells, in: “Microsomes and Drug Oxidations”, A. R. Boobis, J. Caldwell, F. De Matteis and C. R. Elcombe, eds., Taylor & Francis, London, pp 238–247 (1985).Google Scholar
  26. 26.
    W. S. Bowers, P. H. Evans, P. A. Marsella, D. M. Soderlund and F. Bettarini, Natural and synthetic allatotoxins: suicide substrates for juvenile hormone biosynthesis, Science, 217:647–648 (1982).PubMedCrossRefGoogle Scholar
  27. 27.
    R. C. Miall and W. Mordue, Precocene-II has juvenile hormone effects in 5th instar Locusta migratoria, J. Insect Physiol., 26:361–364 (1980).CrossRefGoogle Scholar
  28. 28.
    G. T. Brooks, A. P. Ottridge and D. W. Mace, The effect of some furochromene and benzochromene analogues of precocene-I and benzofuran precursors on Oncopeltus fasciatus (Dallas) and Locusta migratoria migratorioides (R&F), Pest. Sci. 22:41–50 (1988).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • G. T. Brooks
    • 1
  • A. R. McCaffery
    • 1
  1. 1.School of Animal and Microbial SciencesUniversity of ReadingReadingUK

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