Quantitative correlation between molecular similarity and receptor-binding activity of neonicotinoid insecticides

Quantitative correlation between molecular similarity and receptor-binding activity of neonicotinoid insecticides such as imidacloprid and acetamiprid was studied by using a method of similarity index and semi-empirical molecular orbital calculations. A series of compounds having an aromatic ring and a cyclic or acyclic amine moiety with an electron-withdrawing group were subjected to the similarity-activity analysis. Energy-minimum structures and electrostatic properties of the molecules were obtained by MNDO-PM3. The electrostatic similarity of each molecule compared with the most active compounds was found to correlate significantly with the binding activity to nicotinic acetylcholine receptor (nAChR) in honey bee when the two molecules were superimposed to maximize the molecular shape similarity by simplex procedure. This indicates that molecular similarity in terms of electrostatic properties is important for activity, as well as superimposability in terms of molecular shape. A schematic model of interaction between neonicotinoids and nAChR is proposed according to the results of similarity-activity analyses. © 1998 SCI.