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NCSR Demokritos

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Development of environmentally friendly methods for control of insect pests

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Molting accelerating compounds (MACs) or ecdysone agonists

MACs act as insecticides by inducing a premature, lethal moult in the target insects. Because MACs can induce the moult at much lower concentrations than the natural hormone, 20-hydroxy-ecdysone (20E), and are not cleared efficiently from the insect body, the insect remains trapped in the moulting process and dies from desiccation and starvation.

A cell-based screening system for MACs was developed based on the activation of an ecdysone-responsive reporter gene (1) and was used to test a collection of > 200 dibenzoyl hydrazine compounds (2). The activity of the most active compounds in the screen was validated in toxicity tests on larvae of the cotton leafworm, Spodoptera littoralis (3).

Cell-based detection systems for ecdysone agonists or MACs were developed for lepidopteran (3), dipteran (4), coleopteran (5,6) and crustacean species (7,8). Recently, potent activity of dibenzoyl hydrazine compounds was observed in toxicity assays against malaria mosquito (Anopheles gambiae) larvae (9).

 

1. Swevers, L., Kravariti, L., Ciolfi, S., Xenou-Kokoletsi, M., Ragoussis, N., Smagghe, G., Nakagawa, Y., Mazomenos, B., and Iatrou., K. (2004). A cell-based high-throughput screening system for detecting ecdysteroid agonists and antagonists in plant extracts and libraries of synthetic compounds. FASEB J. 18, 134-136. FASEB J. 10.1096/fj.03-0627fje.

2. Wheelock, C.E., Nakagawa, Y., Harada, T., Oikawa, N., Akamatsu, M., Smagghe, G., Stefanou, D., Iatrou, K., and Swevers, L. (2006). High-throughput screening of ecdysone agonists using a reporter gene assay followed by 3-D QSAR analysis of the molting hormonal activity. Bioorganic & Medicinal Chemistry 14, 1143-1159.

3. Soin, T., De Geyter, E., Mosallanejad, H., Iga, M., Martín, D., Ozaki, S., Kitsuda, S., Harada, T., Miyagawa, H., Stefanou, D., Kotzia, G., Efrose, R., Labropoulou, V., Geelen, D., Iatrou, K., Nakagawa, Y., Janssen, C.R., Smagghe, G., and Swevers, L. (2010a). Assessment of species specificity of molting accelerating compounds in Lepidoptera: comparison of activity between Bombyx mori and Spodoptera littoralis by in vitro reporter and in vivo toxicity assays. Pest Management Science 66, 526–535.

4. Soin, T., Swevers, L., Kotzia, G., Iatrou, K., Janssen, C.R., Rougé, P., Harada, T., Nakagawa, Y., and Smagghe G (2010b). Comparison of the activity of non-steroidal ecdysone agonists between dipteran and lepidopteran insects, using cell-based EcR reporter assays. Pest Manag. Sci. 66, 1215-1229.

5. Soin, T., Masatoshi, I., Swevers, L., Rougé, P., Janssen, C.R., and Smagghe, G. (2009). Towards Coleoptera-specific high-throughput screening systems for compounds with ecdysone activity: development of EcR reporter assays using weevil (Anthonomus grandis)-derived cell lines and in silico analysis of ligand binding to A. grandis ligand-binding pocket. Insect Biochem. Mol. Biol. 39, 523-534.

6. Ogura, T., Nakagawa, Y., Swevers, L., Smagghe, G., and Miyagawa, H. (2012). Quantitative evaluation of the molting hormone activity in coleopteran cells established from the Colorado potato beetle, Leptinotarsa decemlineata. Pesticide Biochemistry and Physiology 104, 1–8.

7. Verhaegen, Y., Parmentier, K., Swevers, L., Rougé, P., Soin, T., De Coen, W., Cooreman, K., and Smagghe, G. (2010). The brown shrimp (Crangon crangon L.) ecdysteroid receptor complex: Cloning, structural modeling of the ligand-binding domain and functional expression in an EcR-deficient Drosophila cell line. Gen. Comp. Endocr. 168, 415-423.

8. De Wilde, R., Swevers, L., Soin, T., Christiaens, O., Rougé, P., Cooreman, K., Janssen, C.R., and Smagghe, G. (2013). Cloning and functional analysis of the ecdysteroid receptor complex in the opossum shrimp Neomysis integer (Leach, 1814). Aquat. Toxicol. 130-131, 31-40.

9. Morou, E., Lirakis, M., Pavlidi, N., Zotti, M., Nakagawa, Y., Smagghe, G., Vontas, J., and Swevers, L. (2013). A new dibenzoylhydrazine with insecticidal activity against Anopheles mosquito larvae. Pest Manag. Sci. 69, 827–833.