Effects of anti-ecdysteroid azole analogues of metyrapone on the larval development of the fleshfly, Neobellieria bullata

Based on our previous finding that PIM (phenyl-imidazolyl-metyrapon; 2-(1-imidazolyl)-2-methyl-1-phenylpropan-1-one, 1) is a strong inhibitor of ecdysone 20-monooxygenase (IC50 = 7.89 X 10(-7) M) from the fleshfly, Neobellieria bullata (Parker) and has also a good toxic action in vivo against this insect, 17 imidazole and 1,2,4-triazole analogues of metyrapone were synthesized and evaluated for their action against N. bullata larvae in terms of toxicity, length of larval development, weight of the puparium as well as special symptoms, i.e. malformations of the anterior and posterior spiracles, and of the mandibles. The introduction of p-methoxy (LC50 = 49 mg kg-1 in diet) or p-chloro (LC50 = 97 mg kg-1) substituents on the benzene ring of PIM resulted in a significant increase in toxicity compared to that of metyrapone (LC50 = 561 mg kg-1) and PIM (LC50 = 148 mg kg-1). The hybridization state of the carbon atom adjacent to the benzene ring was not an important factor for toxicity because the acetoxy derivative (13) was almost as toxic as PIM. At least one methyl group was required on the carbon atom adjacent to the azole ring to maintain activity, while an ethyl group (4) enhanced the toxic effect. At the applied doses some compounds including metyrapone itself, extended the duration of the larval development. Only metyrapone and PIM decreased the puparium weight. Several derivatives induced lethal malformations of mandibles as well as the anterior and posterior spiracles.