Ecdysone Agonists: Mechanism and Biological Activity

Abstract

Substituted dibenzoyl hydrazines were described as the first non-steroidal ecdysone agonists in 1988 at Rohm and Haas Research Laboratories (Spring House, Pennsylvania, USA) and are characterized by the prototype compound RH-5849 (1,2-dibenzoyl,1-tert-butyl hydrazine) (Fig. 1; Wing 1988; Wing et al. 1988). The discovery that these synthetic compounds mimic the natural insect moulting hormones or ecdysteroids as 20E (Fig. 1) in both fruitfly Drosophila melanogaster (Meigem) Kc cells and tobacco hornworm Manduca sexta (L.) larvae generated great interest from several perspectives. Such compounds open up new avenues for endocrinological research and crop protection, since they mimic the ecdysteroid mode of action by true competitive binding on the ecdysteroid receptors (EcRs). As such, they introduce a new class of insect growth regulators (IGRs) exhibiting a novel mode of action, based on more insect-specific biochemical sites of action, which makes them interesting due to an enhanced safety to non-target organisms, the likelihood for more favourable public perception and the potential for combating resistance. So, they prove to have a potential use in crop pest control, distinct from juvenile hormone analogues (JHAs) and benzoylphenylurea IGRs. The first compound in this series to be commercialized is tebufenozide [RH-5992, 3,5-dimethylbenzoic acid 1-1(1,1-dimethylethyl)-2(4-ethylbenzoyl) hydrazine] (Fig. 1).