QSAR modeling of neonicotinoid insecticides for their selective affinity towards Drosophila nicotinic receptors over mammalian α4β2 receptors

Neonicotinoids are emerging as a major class of insecticides with promising insecticidal activity having a specific affinity towards the nicotinic acetylcholine receptors (nAChR). A quantitative structure-activity relationship (QSAR) study was performed on some azidopyridinyl neonicotinoids for their selective insecticidal activity over mammalian toxicity. The result showed that increased surface area of the molecules may help to increase the binding affinity of the compounds towards the Drosophila receptor and the presence of the azido group on the other hand may be detrimental towards the affinity. Compounds having low polarity, increased probability of nucleophilic attack at the particular position (N-1), and a higher positive charge at the C-12 position can reduce the binding affinity of these compounds towards the mammalian receptor.