title: An extensive ecdysteroid CoMFA.
abstract: The ecdysteroid agonist activity of 71 HPLC-purified ecdysteroids was measured in the Drosophila melanogaster BII tumorous blood cell line assay. The resultant log(ED50) values, spanning almost 6 orders of magnitude, were used to construct a comparative molecular field analysis (CoMFA) model in which conformations were selected by homology to the crystal structure of ecdysone. Model A was constructed by utilization of the region-focused electrostatic indicator field (q2 = 0.631, r2 = 0.903, 5 components, 4 outliers). Model B made use of region-focused electrostatic and steric indicator fields along with MlogP (q2 = 0.694, r2 = 0.892, 5 components, 4 outliers). The model and its underlying bioassay data support a pharmacophore hypothesis in which ecdysteroid binding is understood to be due principally to the summation of localized interactions from approximately six specific loci. This is in contrast to previous structure-activity relationship hypotheses which are formulated in terms of the presence or absence of essential functional groups, without which ecdysteroid receptor affinity would be completely absent. The present CoMFA model is utilized to predict the activities of heretofore unknown ecdysteroids.
authors: Department of Biological Sciences, University of Exeter, U.K.
authors: L
authors: L
authors: Dinan
authors: R E
authors: RE
authors: Hormann
authors: T
authors: T
authors: Fujimoto
mesh_terms: D000818:Animals; D002460:Cell Line; D003198:Computer Simulation; D004331:Drosophila melanogaster; D026461:Ecdysteroids; D007301:Insect Hormones / Q000819:agonists* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D055672:Static Electricity; D013256:Steroids / Q000819:agonists* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D026461:Ecdysteroids; D007301:Insect Hormones; D013256:Steroids