GPCRs: An advanced technology for managing insect pests
Attempts to reduce the use of synthetic pesticides, especially broad-spectrum insecticides in plant protection and to use alternatives and novel methods for pest control or (“biorational control”) are the challenges of pest control for the twenty- first century. Continued pest management by using insecticide is threatened by the development of insecticide resistance to commercial insecticides (Casida and Durkin, 2013).New mode-of-action chemistries are urgently sought for the management of arthropod pests that reduce the crop yield and transmit disease causing agents. Not only in humans, but also in insects, development, reproduction, metabolism and various behaviours are under the control of neuropeptides and biogenic amines that signal through G-protein coupled receptors (GPCRs) (Caers et al. 2012). Novel insecticide targets potentially exist among the arthropod GPCRs. These proteins comprise a large family of membrane-bound molecules that mediate critical biological processes such as neurotransmission, vision and hormonal regulation. More than 100 different GPCRs have been identified in the genomes of multiple insect species. The dopamine GPCR, AaDOP2, antagonist screen hits amitriptyline and doxepin caused significant lethality in the mosquito bioassay (Meyer et al. 2012). Serotonin GPCRs are involved in many key processes of insect life. No insecticides that target this receptor group are available at this moment. Serotonin receptor agonists/antagonist may form potential lead compound. The (1-[(4-aminophenyl) ethyl]-4-[3-(trifluoromethyl) phenyl] piperazine) PAPP scaffold was used to design and synthesize a series of compounds that were evaluated for biological activity against the armyworm Pseudaletia separate (Vleugels et al., 2015). The pyrokinin (PK) family of neuropeptides plays a multifunctional role in the physiology of insects. Incorporation of the dihydroimidazole motif into active core regions of the PK superfamily of peptides provides a unique strategy for the development of mimetic analogs that can serve either as selective agonists or antagonists of the broad class of PK GPCRs (Nachman, 2014). Such analogs provide leads in the development of novel insect-specific, environmentally favourable pest management agents capable of disrupting PK-regulated physiological systems. These ‘‘proof-of-concept’’ studies sets the stage for target-specific approaches for pest management. GPCRs are potential candidate targets for next generation insecticides and provide opportunities to discover new mode-of-action chemistries for pest management.