Inhibitors of calling behavior of Plodia interpunctella

Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino)-2-oxazoline > 2-(2-ethyl,6-methylanilino)oxazolidine > 2-(2-methyl benzylamino)-2-thiazoline > 2-(2,6-diethylanilino)thiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor. Abbreviation: / AII: 2-(arylimino)imidazolidine AIO: 2-(arylimino)oxazolidine AIT: 2-(arylimino)thiazolidine CBO: 2-(4-chlorobenzylamino)-2-(4-phenyl)oxazoline CDM: chlordimeform Confs: number of conformers DIP: 2-(2,6-diethylphenylimino)piperidine Features/Confs: total number of features divided by the number of conformers (summed over the entire family of conformers) HBA: hydrogen-bond acceptor HBAl: hydrogen-bond acceptor lipid HBD: hydrogen-bond donor Hp: hydrophobic HpAl: hydrophobic aliphatic HpAr: hydrophobic aromatic mp: melting point MTO: 2-(3-methyl benzylthio)-2-oxazoline NI: negative ionizable NIO: 2-(1-naphthylimino)oxazolidine OA: octopamine ODA: 2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazine ODO: 2-phenyl-5,6-dihydro-4H-1,3,4-oxadiazine-5(6H)-one PBAN: pheromone biosynthesis activating neuropeptide PEO: 2-(1-phenylethylamino)-2-oxazoline PI: positive ionizable PIT: 1-(2,6-dimethylphenyl)imidazolidine-2-thione RA: ring aromatic SBO: 2-(substituted benzylamino)-2-oxazoline SBT: 2-(substituted benzylamino)-2-thiazoline STO: 2-(substituted benzylthio)-2-oxazoline ZETA: (Z,E)-9,12-tetradecadienyl acetate