New Analogues of (E)-β-Farnesene with Insecticidal Activity and Binding Affinity to Aphid Odorant-Binding Proteins

Abstract

(E)-β-farnesene is a strong and efficient alarm pheromone in most aphid species. However, applications in agriculture are prevented by its relatively high volatility, its susceptibility to oxidation and its complex and expensive synthesis. To develop novel compounds for aphid control, we have designed and synthesized analogues of (E)-β-farnesene, containing a pyrazole moiety present in several insecticides. Their structures have been confirmed by 1H NMR, elemental analysis, high-resolution mass spectroscopy and IR. Binding activities to three odorant-binding proteins (OBPs) of the pea aphid Acythosiphon pisum have been evaluated and correlated with their structures with reference to (E)-β-farnesene. Several derivatives were shown both to bind to A. pisum OBPs with a specificity similar to that of (E)-β-farnesene and to have aphicidal activity comparable to that of thiacloprid, a commercial insecticide. The compounds synthesized in this work represent new potential agents for aphid population control and provide guidelines to design analogues of (E)-β-farnesene endowed with both insecticidal and repellent activity for aphids.

Computer-aided rational design of novel EBF analogues with an aromatic ring

“…Therefore, the II-4 docking score was lower than the other Scheme 1 Synthesis route for the newly designed EBF analogues D1-D4 docking scores. However, in a previous study, the binding affinities of III-1 and III-2, which have an N-methyl formamide group, were found to be higher than those of II-3 and II-4, respectively, which have an amide group, based on the binding assay results [15]. The results of this study can be explained by the hydrophobicity of III-1 and III-2, which enabled them to penetrate into the cell membrane more easily.…”

“…In our previous work, twelve EBF analogues with a pyrazole or benzene ring were synthesized [8,15], and their binding affinities to ApisOBP7 were measured by recording the fluorescence peak values of different EBF analogues and N-phenyl-1-naphthylamine (1-NPN) during their competitive binding to the protein [13,22]. However, the interaction mode between these EBF analogues and ApisOBP7 was not clear.…”

“…Recently, the crystal structures of insect OBP1, OBP7, OBP4, and OBP14 were successfully solved, and they could stimulate new research on novel insect behavioral controls based on OBPs [16][17][18][19][20][21]. Surprisingly, in our previous work, some EBF analogues with a pyrazole or benzene ring were found to exhibit not only good binding affinity to ApisOBP7 but also good repellent responses to aphids [15]. However, the interaction mechanism between these EBF analogues and OBP7 is unknown, and it is unclear if new analogues can be designed based on the OBP7 binding cavity.…”

“…SaveOBP7 in Hemiptera species was also found to play an important role in EBF recognition [14]. Recently, ApisOBP7 was proposed by Yang et al to bind specifically not only to EBF but also to its analogues with a pyrazole ring [15]. More importantly, some EBF analogues with high binding affinities surprisingly exhibited good repellent responses to aphids [15].…”

“…Recently, ApisOBP7 was proposed by Yang et al to bind specifically not only to EBF but also to its analogues with a pyrazole ring [15]. More importantly, some EBF analogues with high binding affinities surprisingly exhibited good repellent responses to aphids [15]. Moreover, OBP, which is an important protein in insect olfactory recognition, could transfer the bound ligand to downstream olfactory receptors (ORs) to further stimulate insect behavioral responses.…”