The nicotinic acetylcholine receptor (nAChR) has been an insecticide molecular target site of growing importance for many years. It plays a central role in the mediation of fast excitatory synaptic transmission in the central nervous system of insects. Inspired by the stemofoline lactone 'head group' as a topological pharmacophore pattern and structural features of other relevant nAChR agonists, a new bioactive scaffold was found, which resulted in the identification of the butenolide insecticide SivantoTM(common name: flupyradifurone). Flupyradifurone is very versatile in terms of application methods to a variety of crops, exhibits excellent and fast action against a broad spectrum of sucking pest insects and demonstrates resistance breaking properties. It was recently reported that insecticide resistance in the cotton whitefly, Bemisia tabaci is associated with the overexpression of CYP6CM1, a cytochrome P450 monooxygenase which confers metabolic resistance to neonicotinoids and pymetrozine, often resulting in field failures at recommended rates. This enzyme is overexpressed in whitefly populations in many regions in the world as shown by an ELISA-based diagnostics developed for field use. However, flupyradifurone applied at recommended rates was shown to control whiteflies overexpressing CYP6CM1. The absence of flupyradifurone metabolism by CYP6CM1 recombinantly expressed in insect cell lines is supported by molecular docking studies of the substrates imidacloprid and flupyradifurone into the recently published binding site model of the biotype Q variant of CYP6CM1. A cluster analysis of the observed docking poses together with the key residues involved in substrate binding and the influence of the overall substrate shape will be presented.

Flupyradifurone (Sivanto<sup>TM</sup>) and its novel butenolide pharmacophore: Molecular insights and whitefly control

248th National Meeting (2014)

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Flupyradifurone (SivantoTM) and its novel butenolide pharmacophore: Molecular insights and whitefly control

Flupyradifurone (Sivanto^TM) and its novel butenolide pharmacophore: Molecular insights and whitefly control