US EPA

6929024 

Journal Article 

SAR and QSAR Analyses of Substituted Dibenzoylhydrazines for Their Mode of Action as Ecdysone Agonists 

Fujita, T; Nakagawa, Y; , 

2009 

CRC PRESS-TAYLOR & FRANCIS GROUP 

BOCA RATON 

ENDOCRINE DISRUPTION MODELING 

357-377 

WOS:000267704800013 

A series of our Structure-Activity Relationship (SAR) and Quantitative Structure-Activity Relationship (QSAR) studies of synthetic molting hormone agonists, N,N'-dibenzoyl-N-t-butylhydrazines (DBHs) exhibiting insecticidal/larvicidal 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 affinity 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 field 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 findings clearly indicate the physicochemical meaning of parameters significant in the correlation equations to help understand the molecular mechanism of the molting hormonal action especially for lepidopteran insect larvae. 

Devillers, J; 

978-1-4200-7635-6