Faculty of Education, United Graduate School of Agricultural Science, Gifu University, Gifu, Japan.
J Agric Food Chem. 2010 Nov 24;58(22):11832-6. doi: 10.1021/jf102819n. Epub 2010 Oct 25.
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.
具有合适亚烷基间隔基的双-吡虫啉类似物具有植物系统性杀虫性质。亚烷基键合的双-吡虫啉以独特的方式与昆虫烟碱型乙酰胆碱受体（nAChR）结合，其中氯吡啶部分被两个不同且遥远的结构域所包围。庚撑间隔基最佳地桥接这两个亚位点，但连接体本身以相对非特异性的方式结合。本研究检验了以下假设：具有杂芳基桥接的双-吡虫啉类似物可能会与新识别的受体腔发生特定相互作用，从而相对于亚烷基键合衍生物提高效力。值得注意的是，具有呋喃-2,5-二甲撑枢轴的新型双-吡虫啉在具有各种化学型间隔基的类似物中显示出最高的受体效力和杀虫活性。nAChR 结构模型模拟了呋喃-2,5-二甲撑键合的双-吡虫啉的结合位点相互作用，表明呋喃环位于由三个芳香族氨基酸组成的疏水性口袋中，并通过氢键稳定。
