Cytochrome P‐450 Inducers and Inhibitors Interfering with Ecdysone 20‐Monooxygenases and Their Activities during Postembryonic Development of Neobellieria bullata Parker

The cytochrome P-450-dependent microsomal and mitochondrial ecdysone 20-monooxygenase systems convert ecdysone into 20-hydroxyecdysone. The microsomal fraction of fat bodies of zero h wandering stage fleshfly larvae (Neobellieria bullata; Diptera: Sarcophagidae) has a high ecdysone 20- monooxygenase activity. The effects of cytochrome P-450 inhibitors were investigated in vitro on microsomal ecdysone 20-monooxygenase. Metyrapone, fenarimol and certain imidazole derivatives (KK-42, KK-110, KK-135 and PIM) are strong inhibitors. The IC50 value of KK-110, which is the strongest inhibitor, is 2 × 10−7 M. A triazolyl and two cyclopropylamine derivatives have low activity. The activities of different NADPH-cytochrome c (P-450) reductase inhibitors were also assessed; diquat dibromide is a moderate inhibitor of microsomal ecdysone 20-monooxygenase, while paraquat dichloride has no activity. In-vivo experiments with cytochrome P-450 inducers and inhibitors gave the following results: (a) fenarimol, FI-121, precocene-2 caused “permanent” first-instar larvae; (b) barbital, phenobarbital and their sodium salts caused significant delay in larval development; (c) PIM, PTM, metyrapone, KK-42, KK-135, J-2710, RH 5849 and colchicine caused moulting disturbances; (d) J-2710, PIM, PTM, KK-42, KK-135, RH 5849 and colchicine caused lethal spiracle and mandible malformation; (e) KK-110, fenarimol, barbital and phenobarbital caused precocious pupariation.

[1]  B. Darvas,et al.  Lethal disturbances in larval development of Neobellieria bullata caused by metyrapone derivatives , 1991 .

[2]  M. Eto,et al.  Synthesis and insect growth regulatory activity of 1-neopentyl-5-substituted imidazoles. , 1990 .

[3]  B. Darvas,et al.  Effects of the bipyridylium herbicides diquat dibromide and paraquat dichloride on growth and development of Neobellieria bullata (Diptera: Sarcophagidae) larvae. , 1990, Journal of economic entomology.

[4]  R. Feyereisen,et al.  Structure/activity studies on 1,5-disubstituted imidazoles as inhibitors of juvenile hormone biosynthesis in isolated corpora allata of the cockroach Diploptera punctata , 1990 .

[5]  D. Béla Insect steroids, their biosynthesis and/or activity inhibitors. III. Steronoids, anti cholesterol agents, anti progesterone agents, ecdysteronoids, ecdysteroid agonists, NADPH- cytochrome c (P-450) reductase inhibitors, cytochrome P-450 inhibitors, cytochrome P-450 inducers , 1990 .

[6]  L. Gilbert,et al.  Juvenile hormone bisepoxide biosynthesis in vitro by the ring gland of Drosophila melanogaster: a putative juvenile hormone in the higher Diptera. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Smith,et al.  Effects of azadirachtin on insect cytochrome P-450 dependent ecdysone 20-monooxygenase activity. , 1988, Biochemical and biophysical research communications.

[8]  K. D. Wing RH 5849, a nonsteroidal ecdysone agonist: effects on a Drosophila cell line. , 1988, Science.

[9]  B. Dastugue,et al.  20-Hydroxyecdysone induces the expression of one beta-tubulin gene in Drosophila Kc cells. , 1988, Biochimica et biophysica acta.

[10]  H. Bidmon,et al.  Ecdysone synthesis and release by the brain-ring gland complex of blowfly larvae , 1988 .

[11]  R. Feyereisen,et al.  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 , 1988 .

[12]  J. Chambers,et al.  Inhibition of juvenile hormone III biosynthesis by fluoromevalonolactone and citronellyl phenyl imidazoles in isolated corpora allata from the cockroach Periplaneta americana , 1987 .

[13]  C. Hétru,et al.  Further characterization of the 2-deoxyecdysone C-2 hydroxylase from Locusta migratoria , 1987 .

[14]  D W Nebert,et al.  P450 genes: structure, evolution, and regulation. , 1987, Annual review of biochemistry.

[15]  S. Yu Consequences of Induction of Foreign Compound-Metabolizing Enzymes in Insects , 1986 .

[16]  G. Staal Anti Juvenile Hormone Agents , 1986 .

[17]  J. Hoffmann,et al.  STUDIES ON THE C-2 HYDROXYLATION OF 2-DEOXYECDYSONE IN LOCUSTA MIGRATORIA , 1986 .

[18]  H. Eisen Induction of Hepatic P-450 Isozymes , 1986 .

[19]  L. Brattsten,et al.  Enzymes involved in the metabolism of plant allelochemicals , 1986 .

[20]  B. C. Baldwin,et al.  Inhibition of the fucosterol-24(28)-epoxide cleavage enzyme of sitosterol dealkylation in Spodoptera littoralis larvae , 1985 .

[21]  S. Yu,et al.  Induction of Hydrolases by Allelochemicals and Host Plants in Fall Armyworm (Lepidoptera: Noctuidae) Larvae , 1985 .

[22]  E. Hamel,et al.  Structure-function studies with derivatives of 6-benzyl-1,3-benzodioxole, a new class of synthetic compounds which inhibit tubulin polymerization and mitosis. , 1985, Molecular pharmacology.

[23]  J. A. Svoboda,et al.  Ecdysone 20-Monooxygenases , 1984 .

[24]  L. Varjas,et al.  PRECOCIOUS METAMORPHOSIS AND MOULTING DEFICIENCIES INDUCED BY AN ANTI‐JH COMPOUND, FMEV IN THE FALL WEBWORM, HYPHANTRIA CUNEA , 1983 .

[25]  C. Smith,et al.  Detoxification of plant toxins by insects , 1983 .

[26]  E. Hodgson The significance of cytochrome P-450 in insects , 1983 .

[27]  S. L. Wentworth,et al.  A possible role of ecdysteroids in pre-ecdysial tanning in larvae of Sarcophaga bullata (Diptera: Sarcophagidae) , 1982 .

[28]  L. Jurd,et al.  New types of insect chemosterilants. Benzylphenols and benzyl-1,3-benzodioxole derivatives as additives to housefly diet , 1979 .

[29]  L. Gilbert,et al.  Evidence for an α-ecdysone cytochrome P-450 mixed function oxidase in insect fat body mitochondria , 1977, Nature.

[30]  L. C. Terriere,et al.  Insect juvenile hormones: Induction of detoxifying enzymes in the housefly and detoxication by housefly enzymes , 1973 .

[31]  T. Ohtaki On the delayed pupation of the fleshfly, Sarcophaga peregrina Robineau-Desvoidy. , 1966 .