QSAR and mode of action studies of insecticidal ecdysone agonists†

†Presented at the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.

Abstract

A series of our SAR and QSAR studies of synthetic moulting hormone agonists, dibenzoylhydrazines (DBH), exhibiting insecticidal/larvicidal activity are reviewed in this article. We prepared a number of analogues where various substituents are introduced into the two benzene rings of DBH and measured their biological activity using various biological systems. Larvicidal activity was against larvae of the rice stem borer Chilo suppressalis and the moulting 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 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. Comparisons among correlations and with recently revealed X-ray crystallographic findings clearly indicate the physicochemical meaning of parameters significant in the correlation equations to help understanding molecular mechanism of the moulting hormonal action.

†Presented at the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.

Keywords:

• QSAR
• Insecticides
• Larvicides
• N,N′-Dibenzoyl-N-t-butylhydrazines
• Ecdysone analogues
• Ecdysone agonists
• Ecdysone receptor
• Receptor binding

Acknowledgements

The authors express their sincere thanks to Dr. Nobuhiro Oikawa, Mr. Kazunari Hattori, Dr. Chieka Minakuchi, Mr. Takehiko Ogura, and Mr. Toshiyuki Harada for their devoted collaboration. We are also grateful to Professor Guy Smagghe and Dr. Craig Wheelock for their helpful comments and discussions.

Notes

†Presented at the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.