Multidimensional Quantitative Structure-Activity Relationships of Diacylhydrazine Toxicity to Lepidopteran and Coleopteran Insect Pests

Abstract

Insecticidal activity indices, i.e., median lethal dose causing mortality in 50% of insects treated (pLD50) values, of 77 Diacylhydrazines (DAHs) were determined against larvae of the Beet Armyworm (Spodoptera exigua), the rice stem borer (Chilo suppressalis), and the Colorado Potato Beetle (Leptinotarsa decemlineata). A series of multidimensional Comparative Molecular Field Analysis (CoMFA) Quantitative Structure–Activity Relationship (QSAR) models was constructed for each type of insect toxicity, and these models were evaluated by q2 of 67-member training sets and r2 of ten-member test sets. Favored models yielded r2 values in the range of 0.77–0.88, q2 values in the range of 0.54–0.62 after consideration of outliers, test set r2 values in the range of 0.54–0.72, and external q2 values in the range of 0.31–0.58. The structure–activity relationships for each type of insect toxicity can be partially, but not entirely, rationalized in view of Ecdysone Receptor (EcR) LBD sequence alignments and putative contact residues relative to the known crystallized Heliothis virescens EcR LBD/BYI06830 holoreceptor. Alternate ligand poses or LBD remodeling may pertain across members of the DAH chemotype.