Protein structure based rational design of ecdysone agonists.

We review the impact of protein X-ray crystallography on the rational design of insecticides that act as agonists of the ligand-binding domain of the Ecdysone receptor (EcR). As the EcR is a target specific to insects, these compounds potentially constitute new chemical classes of safe insecticides. The increased insight relative to that from ligand-only based (Quantitative) Structure-Activity Relations (QSARs), classical 2D-Hansch type or 3D-CoMFA/CoMSIA (Comparative Molecular Field/Similarity Analysis), is discussed.

Sterol biosynthesis inhibitors. Secondary effects and enhanced in vivo efficacy.

Sterol biosynthesis inhibitors such as the imidazoles and 1,2,4-triazoles are generally regarded as inhibitors of sterol C-14 demethylation. Neither the MIC values nor the data for direct interaction with the cytochrome P-450 responsible for oxidative C-14 methyl removal, however, fully explain the observed in vivo efficacy. The first generation of azoles, which includes clotrimazole and miconazole, has been supplemented by a second generation, and azoles of the new generation are capable of additional effects on sterol biosynthesis.