Quantitative structure-activity studies of octopaminergic ligands against Locusta migratoria and Periplaneta americana

The quantitative structure-activity relationship (QSAR) of octopaminergic agonists and antagonists against the thoracic nerve cord of the migratory locust, Locusta migratoria, was analysed using physicochemical parameters and regression analysis. Sixty-five molecules that employ a single [³H]octopamine (OA) binding criterion were selected. The hydrophobic and electronic nature of the ligands were the most important factors for binding activity: the positive log of octanol-water partition coefficient (Log P), dipole moment (D/M) and negative valence connectivity index (CVI1) terms mean that the more hydrophobic, the larger the DM value and the smaller the VCI1 value, the greater the binding activity. The quantitative structure-activity relationship of 2-(arylimino)oxazolidines (AIOs), 2-(aralkylamino)-2- oxazolines (AAOs), 2-(arylimino)thiazolidines (AITs), 2-(aralkylamino)-2- thiazolines (AATs), arylethanolamines (AEAs) and 1-(substituted- phenyl)imidazolidine-2-thiones (SPITs) in stimulating adenylate cyclase prepared from thoracic nerve cords of the American cockroach Periplaneta americana was examined using parameters calculated by molecular orbital. The hydrophobicity, spatial descriptor and conformational similarity index were the most important factors for adenylate-cyclase activation: the positive solvent-accessible surface (SAS) area log P and negative conformational energy by rigid fitting on OA (CERO) terms mean that the larger the SAS, the more hydrophobic and the smaller CERO, the greater the activity in terms of adenylate-cyclase activation.