Furan-2,5-dimethylene-Tethered Bis-imidacloprid Insecticide Conferring High Potency

Abstract

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.

Azobenzene Modified Imidacloprid Derivatives as Photoswitchable Insecticides: Steering Molecular Activity in a Controllable Manner

“…A 4-fold difference was achieved on AMI-4 and 10 upon photoirradiation. Compounds AMI-9 or AMI-10 have some similarities with the bis-IMI derivatives disclosed by Kagabu et al 49 50 51 . Such bis-IMI’s activity was significantly influenced by the spacer types and distance.…”

“…Such bis-IMI’s activity was significantly influenced by the spacer types and distance. Among various spacers investigated, the heptamethylene or furan-2,5-dimethylene was the optimal bridge 49 50 51 . The N-PhN=NPh-N lengths for trans and cis isomers of AMI-9 or AMI-10 are about 12.29 Ǻ and 6.82 Ǻ or 12.59 Ǻ and 8.14 Ǻ, respectively.…”

“…The shorter or longer distance of the linker may decrease the activity. Furthermore, the lack of heteroatom in the AB linker which is important for stabilizing the interaction with the receptor further attenuated the activity 50 .…”

“…In an effort to understand the structure-activity difference in the receptor level, computational modelling of the most active compounds AMI-10 in its trans and cis form ( Fig. 4A ) was carried out using the insect nAChR surrogate Aplysia AChBP (protein data bank code 2WNJ) 50 52 . The reason we chose 2WNJ here is its ability for adopting the large ligand, which has been verified by Kagabu et al for docking the larger divalent IMI analogues 50 .…”

Cytotoxicity evaluation and apoptosis-inducing effects of furanone analogues in insect cell line SL2

“…To our knowledge, most of the studies about furanone analogues were focused on their antimicrobial activity. However, compounds containing furan ring also attracted much attention owing to their unique mechanisms of action against insects (Paula et al, 2008 andKagabu et al, 2010). Our group had optimized the diphenyl ketones' structures and obtained some furanone analogues.…”