Inhibition of insect cytochrome P-450 by some metyrapone analogues and compounds containing a cyclopropylamine moiety and their evaluation as inhibitors of juvenile hormone biosynthesis

Two metyrapone analogues, 2‐(l‐imidazolyl)‐2‐methyl‐l‐phenyl‐l‐pro‐panone (A‐phenyl‐B‐imidazolyl‐metyrapone; III) and 2‐methyl‐l‐phenyl‐2‐{1,2,4‐triazol‐l‐yl)‐l ‐propanone (A‐phenyl‐B‐triazolyl‐meiyrapone; IV) as well as two cyclopropylamine derivatives. N‐cyclopropyl‐4‐icrt‐butylbenzylamine (V) and N‐cyclopropyl‐4‐(3,7‐dimethyl‐7‐methoxy‐octyloxy)benzamide (cyclopropylamine acylated with a JH analogue acid of known structure; VI) were synthesized and evaluated in biological assays for JH biosynthesis on cockroach, Diploptera punctata corpora allata and egg growth in adult cockroach as well as for mixed function oxidase activities, i.e. epoxidation of aldrin to dieldrin and O‐demethylation of 7‐methoxy‐4‐methylcoumarin to 7‐hydroxy‐4‐methylcoumarin on microsomes from housefly, Musca domestica, abdomen and from cockroach midgut. Compound VI was a good in‐vitro inhibitor of JH biosynthesis, but it had significantly lower activities in the assays for inhibition of microsomal cytochrome P‐450. Compound IV and metyrapone had moderate activity as inhibitors of oocyte growth. Compounds III, IV and V were more potent inhibitors of housefly aldrin epoxidation than metyrapone and they inhibited the enzyme activity by almost 100% at 02mM, while in cockroach midgut microsome assay metyrapone was more potent than these three compounds.