EFFECTS OF ANTI-ECDYSTEROID AZOLE ANALOGS OF METYRAPONE ON THE LARVALDEVELOPMENT 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 inhibito r of ecdysone 20-monooxygenase (IC50 = 7.89 x 10(-7) M) from the flesh fly, Neobellieria bullata (Parker) and has also a good toxic action in vivo against this insect, 17 imidazole and 1,2,4-triazole analogues o f metyrapone were synthesized and evaluated for their action against N . bullata larvae in terms of toxicity, length of larval development, w eight of the puparium as well as special symptoms, i.e. malformations of the anterior and posterior spiracles, and of the mandibles. The int roduction of p-methoxy (LC(50) = 49 mg kg(-1) in diet) or p-chloro (LC (50) = 97 mg kg(-1)) substituents on the benzene ring of PIM resulted in a significant increase in toxicity compared to that of metyrapone ( LC(50) = 561 mg kg(-1)) and PIM (LC(50) = 148 mg kg(-1)). The hybridiz ation 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 la rval development. Only metyrapone and PIM decreased the puparium weigh t. Several derivatives induced lethal malformations of mandibles as we ll as the anterior and posterior spiracles.