Anti-juvenile Hormone Activity Research Articles

Synthesis and anti-juvenile hormone activity of 2,2-dimethl-1,2-dihydroquinoline derivatives. Nitrogen analogues of precocene I and II.

A synthesis of nitrogen analogues of the natural insect anti-juvenile hormones precocene I and II is reported. The crucial step of this synthesis is thermal cyclization of the N-alkynylaniline 3 into the corresponding 1,2-dihydroquinoline when promoted by a copper catalyst. Biological testing of the anti-juvenile hormone activity was carried out against Callosobruchus chinensis by observing the inhibition of eclosion. The 7-methoxy analogue showed higher activity than the 6,7-dimethoxy analogue. However, the former showed lower activity than precocene I.

Design of novel insect anti-juvenile hormones: allylic alcohol derivatives

Three analogues of 3,3-dimethyl-2-propenol (dimethylallyl alcohol) were synthesized and found to possess anti juvenile hormone activity when assayed on lepidopterous insect species (particularly the tobacco hornworm, Manduca sexta). The most active compound of those described, 3,3-dichloro-2-propenyl hexanoate, caused precocious metamorphosis, inhibited juvenile hormone (JH) biosynthesis in vitro, and reduced JH titers in vivo.

Synthesis and anti-juvenile hormone activity of 1-substituted-5-((E)-2,6-dimethyl-1,5-heptadienyl)imidazoles.

A new series of 1-substituted-5-[(E)-2, 6-dimethyl-1, 5-heptadienyl]imidazoles were prepared and bioassayed for anti-juvenile hormone activity on the silkworm, Bombyx mori. The compounds induced unequivocal precocious metamorphosis in the 3rd and 4th instar larvae by topical application. Of the compounds tested, l-benzyl-5-[(E)-2, 6-dimethyl-1, 5-heptadienyl] imidazole (KK-42) proved to be the most active compound eliciting 100% of precocious pupation at 2 μg/larva on the 4th instar larvae. The E isomer showed considerably higher activity than the corresponding Z isomer. The anti-juvenile hormone effect of KK-42 was counteracted by simultaneous application of JH I or methoprene.

Synthesis and anti-juvenile hormone activity of 1-citronellyl-5-substituted imidazoles.

A number of 1-citronellyl-5-substituted imidazoles were synthesized and bioassayed on the silkworm, Bombyx mori, in order to assess their anti-juvenile hormone activity. Most of the 1-citronellyl-5-substituted imidazoles induced precocious metamorphosis in the 3rd and 4th instar larvae of B. mori by topical application. The percentage of precocious metamorphosis correlated well with the dosage. Among the compounds tested, l-citronellyl-5-(2-chlorophenyl)imidazole (8) and the 2-methylphenyl analog 10 showed the highest activity. When compounds 8 and 10 were applied to the 4th instar larvae at 10 μg/larva, precocious pupation was induced in 100% without any lethal effects.

Antigonadotropic and antiallatal effects of precocene II in the firebrat, Thermobia domestica (Thysanura, Lepismatidae)

The sensitivity of an apterygote insect to precocene II was investigated for the first time in females of Thermobia domestica. Topical applications of this compound, which has been said to possess anti-juvenile hormone activity, were carried out at various times in the postecdysial period of a reproductive cycle, during intense vitellogenesis in the terminal oöcytes. The effects of treatment were observed on mortality, fecundity, insemination and also on the ultrastructure of corpora allata; they depend on the dose used and on the day of treatment. A single application of 10 μg/insect at the beginning of the postecdysial period induces antigonadotropic effects in females reared both with and without males. The effects of precocene add to those of non-insemination, which also elicits inhibition of oöcyte maturation. In addition, the cytotoxic action of precocene, leading to degeneration of the corpora allata, which is most probably irreversible, was demonstrated.

Effects of three compounds with anti-juvenile hormone activity and a juvenile hormone analogue on endogenous juvenile hormone levels in the tobacco hornworm, Manduca sexta

The ability of three anti-juvenile hormones and one juvenile hormone analogue to reduce in vivo juvenile hormone levels in Manduca sexta has been investigated. Two compounds. FMev (tetrahydro-4-fluoromethyl-4-hydroxy-2 H-pyran-2-one) and ETB (ethyl-4-[2-( tert-butylcarbonyloxy)butoxy]-benzoate) reduced the titres of juvenile hormones I and II to near the levels of detection in topically treated larvae. Precocene III (7-ethoxy-6-methoxy-2,2-dimethylchromene) was inactive but the juvenile hormone analogue hydroprene was as effective as the two anti-juvenile hormones in reducing endogenous juvenile hormone titres in larvae. FMev was also shown to reduce the level of juvenile hormones II and III in pharate adults.

Studies on Biologically Active Heterocyclic Compounds

On the basis of the natural product models and biochemical designs, attempts were made to find leads for the development of new pesticide chemicals. Antilipidemic agents of several different chemical classes and cis-7-chloro-3a, 8b-dihydro-3a-methylfuro[3, 4-b]benzofuran-3 (1H)-one, which inhibited HMG-CoA reductase activity in rats in vivo, showed ovicidal activity against the eggs of azuki bean weevils, Callosobruchus chinensis, but failed to produce clear anti-juvenile hormone (JH) activity. A number of imidazole compounds possessing a JH-like terpene chain, designed to be potential inhibitors of JH biosynthesis, were synthesized and bioassayed on the silkworm, Bombyx mori larvae. New compounds, 1-geranyl-5-phenylimidazole (A-1) and the 1-citronellyl analog (A-2), showed remarkable anti-JH activity. When treated to the third instar larvae, miniature pupae were formed after molting to the fourth instar larvae. The fifth instars were also omitted by treatment of the fourth instar larvae. The presence of a phenyl group at the 5 position of the imidazole ring is essential for anti-JH activity. The introduction of a methoxy group in the 7 position of the terpene chain of A-1 and A-2 eliminated or decreased the activity. The anti-JH effects of A-1 and A-2 on B. mori larvae were completely blocked by simultaneous application of such a JH mimic as methoprene. Benzimidazoles having a terpenoid moiety, 1-(3, 7-dimethyl-7-methoxy-2-octenyl)-2-methylbenzimidazole (B-1) and the 7-ethoxy analog (B-2), showed high insecticidal activity against houseflies and green rice leafhoppers, Nephotettix cinticeps. They inhibited also larval molting of B. mori at low doses when applied topically to the larvae 1-2 days before erdysis. 8-Isopropyl-6-oxabicyclo[3.2.1]octan-7-one (trans-lactone) with a partial skeleton of picrotoxinin, which is an antagonist of γ-aminobutyric acid, and some related lactones were synthesized and their insecticidal activities were assayed on houseflies. In the insecticidal activity of the lactone compounds the configuration of the isopropyl group at C8-position played an important role. Thus trans-lactone had the highest activity. Ninety s-triazine derivatives were prepared by the reaction of amino acids and peptides with substituted biguanides and bioassayed on plant growth. Among the tested compounds the s-triazine derived from leucylleucine exhibited the highest growth inhibitory activity on rice.

Natural and Synthetic Allatotoxins: Suicide Substrates for Juvenile Hormone Biosynthesis

Cytotoxic agents with antijuvenile hormone activity in insects have been discovered. Their mechanism of action may involve an oxidative bioactivation into a reactive quinone methide.

How Anti-Juvenile Hormones Work

SYNOPSIS. TWO compounds which possess anti-juvenile hormone activity in insects have been isolated and identified from the plant Ageratum houstonianum. These compounds, called precocenes, have been shown to inhibit the development of the insect corpus allatum (CA) and/or destroy the CA in sensitive species. The action of the precocenes can be seen to affect only those CA which are actively synthesizing and secreting the juvenile hormone. Structure-optimization studies of the precocenes reveal that the 3,4-double bond must be present and unsubstituted for biological activity to occur. In vivo and in vitro studies reveal that the precocenes are very probably converted into reactive epoxides which undergo facile reaction with nucleophiles since histological examination of precocene-inactivated CAs indicate a direct cytotoxic action of the precocenes on the parenchymal cells of the CA. The most likely mode of action would appear to involve the alkylation of macromolecular cellular elements by a reactive epoxide or similar activated precocene intermediate.

How Anti-Juvenile Hormones Work

Synopsis. Two compounds which possess anti-juvenile hormone activity in insects have been isolated and identified from the plant Ageratum houstonianum. These compounds, called precocenes, have been shown to inhibit the development ofthe insect corpus allatum (CA) and/or destroy the CA in sensitive species. The action of the precocenes can be seen to affect only those CA which are actively synthesizing and secreting the juvenile hormone. Structure-optimization studies of the precocenes reveal that the 3,4-double bond must be present and unsubstituted for biological activity to occur. In vivo and in vitro studies reveal that the precocenes are very probably converted into reactive epoxides which undergo facile reaction with nucleophiles since histological examination of precocene-inactivated CAs indicate a direct cytotoxic action of the precocenes on the parenchymal cells of the CA. The most likely mode of action would appear to involve the alkylation of macromolecular cellular elements by a reactive epoxide or similar activated precocene inter? mediate.

Fluoromevalonate acts as an inhibitor of insect juvenile hormone biosynthesis

The potential of analogues of insect juvenile hormones (JHs) for pest control has been demonstrated by the application of methoprene for the selective control of certain insects, including several mosquito species, the cigarette beetle and the hornfly1. Compounds that impede JH production could offer a potentially more attractive method of control because accelerated metamorphosis would shorten the lifetime of the larvae, the stage that usually does maximum damage to the host plant. Of the few anti-juvenile hormone (AJH) agents described2–5, only precocenes evoke all the required biological responses, but they affect a few insect taxa of minor economic importance. Their activity is thought to result from cytotoxicity6,7 in the corpora allata. In view of similarities between the biosynthesis of the carbon skeletons of insect JHs8,9 and farnesyl pyrophosphate (a precursor of steroids and other terpenoids10), compounds that inhibit the early steps in the biosynthesis of cholesterol might be expected to suppress JHs. Although this concept has already been explored without success11,12, we now report the inhibition of juvenile hormone biosynthesis (AJH activity, see Table 1 legend) by a fluorinated mevalonate tetrahydro-4-fluoromethyl-4-hydroxy-2H-pyran-2-one, FMev, Fig. 1) which until now was known only to be hypocholesterolaemic13–15.