Three-dimensional common-feature hypotheses of inhibitors of calling behaviour and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella.
Some octopamine (OA) agonists were found to suppress the calling behaviour and pheromone biosynthesis in vitro of the Indian meal moth, Plodia interpunctella (Hübner), a stored-product pest. Compounds were screened using a calling behaviour bioassay of female P interpunctella. Three active derivatives, with activity at the nanomolar level, were identified. In order of decreasing pheromonostatic activity these were: 2-(2-ethyl-6-methylanilino)oxazolidine > 2-(2,6-diethylanilino)thiazolidine > 2-(2,6-diethylanilino)oxazolidine. These compounds showed also in vitro inhibitory activities in de novo pheromone biosynthesis. Three-dimensional pharmacophore hypotheses were built from a set of 19 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a ring aromatic group (RA), a positive ionizable group (PI) and two hydrophobic aliphatic (HpA1) features was considered to be essential for inhibitory activity in the calling behaviour and pheromone biosynthesis in vitro. Active compounds mapped well onto all the RA, PI and HpA1 features of the hypothesis. Less-active compounds were shown not to achieve the energetically favourable conformation which was found in the active molecules in order to fit the 3-D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behaviour and PBAN-stimulated incorporation of radioactivity is by OA-agonistic activity.
Hirashima
Akinori
A
Department of Applied Genetics and Pest Management, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. ahirasim@agr.kyushu-u.ac.jp
Eiraku
Tomohiko
T
Shigeta
Yoko
Y
Kuwano
Eiichi
E
Taniguchi
Eiji
E
Eto
Morifusa
M
D000085:Acetates / Q000378:metabolism*; D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002250:Carbon Radioisotopes; D005260:Female; D007814:Larva / Q000187:drug effects / Q000502:physiology; D007915:Lepidoptera / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009655:Octopamine / Q000819:agonists; D010080:Oxazoles / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D010675:Pheromones / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011679:Pupa / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D053778:Thiazolidines
C471116:2-(2,6-diethylanilino)oxazolidine; C471115:2-(2,6-diethylanilino)thiazolidine; C471117:2-(2-ethyl-6-methylanilino)oxazolidine; D000085:Acetates; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D010080:Oxazoles; D010675:Pheromones; D013844:Thiazoles; D053778:Thiazolidines; C064210:oxazolidine; D009655:Octopamine