RESUMEN

Structure-activity relationships of diazinoyl nicotinic insecticides (diazinoyl isomers and 5- or 6-substituted pyrazin-2-oyl analogues) are considered in terms of affinity to the insect nicotinic acetylcholine receptor (nAChR) and insecticidal activity against the imidacloprid-resistant brown planthopper. Among the test compounds, 3-(6-chloropyridin-3-ylmethyl)-2-(pyrazinoyl)iminothiazoline shows the highest potency in nAChR affinity and insecticidal activity. Aplysia californica acetylcholine binding protein (AChBP) mutants (Y55W + Q57R and Y55W + Q57T) are utilized to compare molecular recognition of nicotinic insecticides with diverse pharmacophores. N-nitro- or N-cyanoimine imidacloprid or acetamiprid, respectively, exhibits a high affinity to these AChBP mutants at a similar potency level. Intriguingly, the pyrazin-2-oyl analogue has a higher affinity to AChBP Y55W + Q57R than that to Y55W + Q57T, thereby indicating that pyrazine nitrogen atoms contact Arg57 guanidinium and Trp55 indole NH. Furthermore, nicotine prefers AChBP Y55W + Q57T over Y55W + Q57R, conceivably suggesting that the protonated nicotine is repulsed by Arg57 guanidinium, consistent with its inferior potency to insect nAChR.

Asunto(s)

Hemípteros , Proteínas de Insectos , Insecticidas , Neonicotinoides , Receptores Nicotínicos , Animales , Insecticidas/química , Insecticidas/farmacología , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/genética , Hemípteros/química , Hemípteros/genética , Hemípteros/efectos de los fármacos , Hemípteros/metabolismo , Relación Estructura-Actividad , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/química , Neonicotinoides/química , Neonicotinoides/farmacología , Neonicotinoides/metabolismo , Nitrocompuestos/química , Nitrocompuestos/farmacología , Nitrocompuestos/metabolismo , Aplysia/química , Aplysia/metabolismo , Aplysia/genética , Nicotina/química , Nicotina/metabolismo , Nicotina/análogos & derivados , Nicotina/farmacología