ABSTRACT
A series of our Structure-Activity Relationship (SAR) and Quantitative StructureActivity Relationship (QSAR) studies of synthetic molting hormone agonists, N,N′-dibenzoyl-N-t-butylhydrazines (DBHs) exhibiting insecticidal/larvicidal
13.1 Introduction ................................................................................................. 358 13.2 Biological Activities of DBHs to Rice Stem Borers, Chilo suppressalis .... 359
13.2.1 Classical QSAR Analysis of Insecticidal Activity ......................... 359 13.2.2 Classical QSAR Analysis of the N-Acetylglucosamine
Incorporation into the Integument ................................................. 361 13.2.3 The AAR and Classical QSAR of the Cellular-Level Activity ...... 362 13.2.4 Receptor Binding and Its Relationship with Tissue-Level
Activity ...........................................................................................366 13.2.5 Validation of the (Q)SAR Signicance with X-ray
Crystallography of the Ligand-EcR Complexes of the Tobacco Budworm ............................................................... 367
13.3 QSAR Examinations for the Activation of Silkworm EcR and Homology Modeling of Its 3D Architecture ........................................ 368 13.3.1 Classical QSAR Analysis of the EcR Activation ........................... 368 13.3.2 3D-QSAR (CoMFA) Analysis of the Receptor Activation ............ 370 13.3.3 Homology Modeling of the Silkworm EcR ................................... 373
13.4 Conclusions .................................................................................................. 374 Acknowledgments .................................................................................................. 375 References .............................................................................................................. 375
activity are reviewed in this chapter. We prepared a number of analogs where various substituents are introduced into the two benzene rings of DBH and measured their activity using various biological systems. Larvicidal activity was against larvae of the rice stem borer Chilo suppressalis and the molting hormone activity was in terms of the stimulation of N-acetylglucosamine incorporation in a cultured integument system of the same insect species. Binding afnity to the ecdysone receptor was assayed with intact Sf-9 cell lines in which the absorption, distribution, metabolism, and excretion (ADME) processes are negligible as well as using receptor proteins obtained by in vitro translation of the responsible cDNA cloned from cell-free preparation of integumentary tissue of C. suppressalis. Variations in the biological activity indices were either correlated between two types of activity or correlated using physicochemical molecular and substituent parameters in terms of the classical QSAR. Three-dimensional QSAR (comparative molecular eld analysis [CoMFA]) for the activity of the receptor response using cultured cells of Bombyx mori has also been explored. Comparisons among correlations and with recently revealed X-ray cocrystallographic ndings clearly indicate the physicochemical meaning of parameters signicant in the correlation equations to help understand the molecular mechanism of the molting hormonal action especially for lepidopteran insect larvae.
