QSAR Studies of Picrodendrins and Related Terpenoids — Structural Differences Between Antagonist Binding Sites on GABA Receptors of Insects and Mammals

Abstract

γ -Aminobutyric acid (GABA), an inhibitory neurotransmitter, binds to the GABA_A (ionotropic) receptor, to regulate the central nervous system of vertebrates. Insects have similar ionotropic receptors with different pharmacological properties, and, as a result, their GABA receptors represent promising targets for insecticides. Recently, 3D-QSAR analyses for insecticidal activity (against houseflies) and competitive activity against the specific [³⁵S]tert-butylbicyclophosphorothionate (TBPS) binding (to rat brain membranes) of some picrotoxinin-type GABA antagonists, including γ -BHC, endosulfan, bicyclophophates, dioxatricyclododecenes (DTD) and related compounds, were carried out¹ using comparative molecular field analysis (CoMFA). The CoMFA results showed that similarities and dissimilarities in sterically and electrostatically favourable and forbidden regions on the molecule were reflected in the insecticidal and rat-receptor binding activities.