Furan-2,5-dimethylene-tethered bis-imidacloprid insecticide conferring high potency.
Bis-imidacloprid (bis-IMI) analogues with suitable alkylene spacers have plant-systemic insecticidal properties. The alkylene-tethered bis-IMI binds in a unique mode to the insect nicotinic acetylcholine receptor (nAChR) wherein the chloropyridine moieties are embraced by two distinct and distant domains. The heptamethylene spacer optimally bridges these two subsites, yet the linker itself binds in a relatively nonspecific manner. This investigation examines the hypothesis that a bis-IMI analogue with a heteroaromatic tether, which undergoes specific interaction(s) with the newly recognized receptor cavity, may enhance the potency relative to those of the alkylene-tethered derivatives. Remarkably, a novel bis-IMI with a furan-2,5-dimethylene fulcrum showed highest receptor potency and insecticidal activity among the analogues with various chemotype spacers. The nAChR structural model, simulating the binding site interactions of the furan-2,5-dimethylene-tethered bis-IMI, reveals that the furan ring is nestled in a hydrophobic pocket, consisting of three aromatic amino acids, and is stabilized via hydrogen bonding.
Kagabu
Shinzo
S
Faculty of Education, United Graduate School of Agricultural Science, Gifu University, Gifu, Japan. kagabus@gifu-u.ac.jp
Ohno
Ikuya
I
Tomizawa
Motohiro
M
Durkin
Kathleen A
KA
Matsuura
Ryota
R
Uchiyama
Daiki
D
Nagae
Nozomi
N
Kumazawa
Satoru
S
D000818:Animals; D001665:Binding Sites; D005260:Female; D006793:Houseflies / Q000737:chemistry / Q000187:drug effects; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D007306:Insecticides / Q000737:chemistry* / Q000494:pharmacology*; D008968:Molecular Conformation; D000073943:Neonicotinoids; D018733:Nicotinic Antagonists; D009574:Nitro Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry; D013329:Structure-Activity Relationship
D007093:Imidazoles; D019476:Insect Proteins; D007306:Insecticides; D000073943:Neonicotinoids; D018733:Nicotinic Antagonists; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; C082359:imidacloprid