Anti-juvenile Hormone Research Articles

Synthesis of two optical isomers of the insect anti-juvenile hormone agent fluoromevalonolactone(FMev) and their biological activities.

The optical isomers (R)-(-)- and (S)-(+)-tetrahydro-4-fluoromethyl-4-hydroxy-2H-pyran-2-one (fluoromevalonolactone, . FMev) of the insect anti-juvenile hormone were synthesized by using combined enzymatic and chemical methods, and their biological activities were examined by using the silkworm Bombyx mori L. It was found that the observed anti-juvenile hormone and insecticidal activity against Bombyx mori after topical treatment with racemic FMev was due to the (R)-(-)-enantiomer of FMev, the (S)-(+)-enantiomer being inactive.

Effects of different anti-juvenile hormone agents on the fecundity of the female cattle tick Boophilus microplus

Ten different compounds which have been reported to have anti-juvenile hormone effects in some insects were applied topically to Boophilus microplus females. Five-hundred micrograms of precocenes (1, 2, or 3) prevented oviposition in 20 to 50% of the treated females. The remaining females oviposited a reduced number of desiccated eggs. Three analogs of precocene tested also inhibited oviposition in some females but did not seriously reduce the egg yield in others. Five-hundred micrograms of piperonyl butoxide per female prevented oviposition in 20% of the animals and also reduced the egg yield in the remaining ticks. In contrast, however, the inhibitors ETB and KK-42 did not produce the same effect as the previous compounds at similar doses. The most active compound was fluoromevalonate (FMev), which proved to be lethal at a dose of 200 μg per female. A decrease in egg yield was noted with doses as low as 5 μg of this compound per female. However, topical application or injection of juvenile hormone analogs was not effective in restoring the egg yield in females treated with 50 μg FMev. It is therefore difficult to interpret the effects of this compound as anti-JH. In addition, topical application of FMev induced an ulceration in the cuticle which did not appear when the females were treated with similar doses of mevalonolactone.

The effect of some furochromene and benzochromene analogues of 2,2‐dimethyl‐7‐methoxychromene (precocene I) and benzofuran precursors on Oncopeltus fasciatus (dallas) and Locusta migratoria migratorioides (R&F)

AbstractAs part of an extensive study on insect antijuvenile hormones (AJH) structurally related to 2,2‐dimethyl‐7‐methoxychromene and 6,7‐dimeth‐oxy‐2,2‐dimethylchromene (precocenes I and II, respectively), four furophenols, six furochromenes, three benzofuran derivatives and two benzochromenes were tested for biological effects on Oncopeltus fasciatus and Locusta migratoria. Exposure to ajar deposit of the chemical was used for O. fasciatus and topical application in acetone for L. migratoria, with precocenes I and II as standards for comparison. All compounds were toxic to O. fasciatus and in some cases, this may have concealed any potential AJH activity, which was not observed for any compound tested. Toxicity to L. migratoria was less evident and three of the furochromene derivatives, allprecocene‐I (PI) analogues, showed AJH activity seven to ten‐fold lower than that of PI. Neither of the benzochromenes tested showed any AJH activity. The results are discussed in terms of the known structure‐activity relationships for precocene‐like AJH activity.

Synergistic action of diethyl maleate on the morphogenetic and antigonadotropic activity of precocenes on the seed bug Oxycarenus Iavaterae (F.)

AbstractFreshly ecdysed‐third instar larvae and adult females of the seed bug Oxycarenus Iavaterae were treated with diethyl maleate (1 or 10 μg/specimen, topically applied), a commonly used depletor of glutathione levels, prior to the application of model precocenes (P1, P2, and EP2; 1–10 μg/specimen, topically applied). The combined treatment resulted in a significant increase of the characteristic antijuvenile hormone effects elicited by the above allatocidins, namely, induction of precocious metamorphosis in larvae and inhibition of ovarian development in adult females. These results, which indicated that diethyl maleate exerted a definite synergistic action, constitute the first example of a synergism strategy to the improvement of precocene activity.

The evaluation of anti juvenile hormones using last stadium larvae of the cabbage looper, Trichoplusia ni (Hübner)

Treatment of prepupae of the cabbage looper, Trichoplusia ni (Hübner), with the anti juvenile hormone (AJH) fluoromevalonolactone (FMev) reduces juvenile hormone esterase (JHE) activity and either delays or inhibits the normal larval-pupal ecdysis in a dose-dependent manner, resulting in the formation of pupae with a suite of characteristic abnormalities. A variety of putative AJHs were evaluated using these teratogenic effects and changes in JHE activity as indicators of AJH activity. Like FMev, the compactin analog L-643,049-01K01 and, at very high doses, 3,3-dichloro-2-propenyl hexanoate (DPH) behaved as AJHs. FMev and L-643,049-01K01 were most effective when larvae were treated at gut purge, while DPH was the most effective after the initiation of spinning behavior.

Threshold Size for Precocious Metamorphosis by an Anti-Juvenile Hormone in Silkworm Larvae, Bombyx mori L.

Silkworm larvae. Bombyx mori L., 3rd and 4th (Penultimate) instars, were treated with an anti-juvenile hormone, 1-citronellyl-5-phenylimidazole (KK-22) in the artificial diet. Relationships between larval body weights at the end of instar and head capsule width of the next instar were investigated to confirm the presence of threshold size factors for precodicous metamorphosis. The 4th instar larvae with head capsule width wider than 2.9 mm after treatments of KK-22 at the 3rd instar were induced into precocious pupation. The 4th instar larvae applied with KK-22 increased their body weight during the instar, and a precocious pupation was observed in larvae with body weight of 1.6 times that of controls. Both head capsule width and body weight at presumed final instar seemed important factors for precocious metamorphosis.

Disruptive developmental effects of benzyl-1,3-benzodioxole derivatives on unparasitized and parasitized Manduca sexta larvae

Treatment of tobacco hornworm larvae with the benzyl-1,3-benzodioxole derivative J-2710 immediately after ecdysis to the fourth instar disrupted development either during the moult to the fifth instar or shortly thereafter. Larvae given topical applications of 100 μg J-2710 in 1 μl acetone suffered 100% mortality, often after secreting moulting fluid in large pockets between the epidermis and the cuticle later in the fourth instar. Larvae that successfully ecdysed had abnormalities of the mouthparts and cervix that interfered with normal feeding, inhibiting growth in the fifth instar. Larvae of the gregarious endoparasitic wasp Cotesia congregata (=Apanteles congregatus) frequently failed to emerge from host Manduca sexta larvae treated with high doses of J-2710, particularly when the host failed to feed normally. Less potent disruptive effects on Manduca and Cotesia were seen after treatment of larvae with the derivatives J-3370 and J-2581. No anti-juvenile hormone action of J-2710 was observed. J-2710-treated M. sexta larvae showed no precocious metamorphosis and the developmental effects of J-2710 were not prevented by co-application of the juvenile hormone analogue methoprene in doses ranging from 1 to 100 μg/larva. Moreover, J-2710 had no effect on the action of methoprene in the black larval assay for juvenile hormone-like activity, unlike results reported to occur using the Galleria wax wound assay.

Developmental regulation of juvenile hormone esterase in Trichoplusia ni: Its multiple electrophoretic forms occur during each larval ecdysis

Juvenile hormone esterase activity has been found during the intramoult period of each larval stadium in Trichoplusia ni. The activity is indistinguishable from that occurring during the final larval stadium, on the basis of its four isoelectric forms and kinetic data. The 4th- to 5th-instar intramoult peak in activity also occurs in other Lepidoptera ( Heliothis virescens, Spodoptera exigua, Manduca sexta and Hyphantria cunea). Further, the final species also possessed a peak of activity during the intramoult period to the penultimate larval instar. The findings have important implications for the current concept that the function of juvenile hormone esterase is, by reason of its anti-juvenile hormone action, an enzyme of the last larval instar which enables metamorphosis to begin.

Induction of trimolter from tetramolter and increase of silk production by repeated treatments with anti-juvenile hormone

Induction of trimolter from tetramolter and increase of silk production by repeated treatments with anti-juvenile hormone

Effects of anti-juvenile hormone on mixed infection of infectious flacherie virus and bacteria in silkworm larvae

Effects of anti-juvenile hormone on mixed infection of infectious flacherie virus and bacteria in silkworm larvae

A role for juvenile hormone and the effects of so-called anti-juvenile hormones in Glossina morsitans

Topical application of the juvenile hormone analogue ZR 0515 to young puparia of Glossina morsitans morsitans caused developmental abnormalities consistent with the untimely presence of juvenile hormone at metamorphosis. Adults emerged with abdominal defects and failed to expand correctly. However, surgical allatectomy of adult females failed to prevent normal reproduction and the apparent abortifacient effect of synthetic juvenile hormone (ZR 0515) was found to be a function of the amount of solvent used in its application rather than to an effect of the hormone itself. It is concluded that juvenile hormone plays its classical role in development in tsetse but we find no evidence that it regulates the gonotrophic cycle in this insect. It was surprising therefore to find that one of the benzyl-1,3-benzodioxoles, (J3370), described in the literature as anti-juvenile hormones produced ovarian atrophy and either temporary or permanent sterility according to dose and timing of topical applications to puparia or to adult G. m. morsitans females. At least one and usually two oöcytes developed normally and were ovulated by females sterilized either as adults or as 3rd instar larvae within the puparium. However, juvenile hormone replacement therapy in the form of topical applications of ZR 0515 before, after or both before and after dosing an adult female with J3370 did not prevent sterility induction. The effects of J3370 on the ovaries of Glossina in any case are inconsistent with an anti-juvenile hormone role for this compound since they correspond to none of the lesions normally associated with the absence of juvenile hormone. Neither could the juvenile hormone induced abnormalities associated with metamorphosis in Glossina be attenuated by J3370. Hence, it is concluded that J3370 does not act as an anti-juvenile hormone in tsetse and its description as such in other insects requires re-appraisal.

The effect of juvenoids, anti juvenile hormone agents, and several intermediates of juvenile hormone biosynthesis on the in vivo juvenile hormone levels in Manduca sexta larvae

JH levels in Manduca sexta larvae were suppressed in a dose dependent fashion following topical treatment with either the potent juvenoids fenoxycarb or hydroprene, or the anti juvenile hormone (AJH) agent (3R,S)- fluoromevalonolactone (FMev>). We determined ED 50 values, expressed as the amount of substance (applied topically to early third stadium larvae) required to lower JH titer (determined in the early fourth stadium) by 50%; these values were 0.001, 0.1 and 3 μg for fenoxycarb, hydroprene, and FMev>, respectively. Combined enzymatic and chemical methods were used to prepare a sample containing predominatly (−)FMev>. Comparison of dose-response curves obtained following treatment of M. sexta larvae with (−)FMev>;, versus treatment with racemic FMev>f, confirmed that the (−)enantiomer is the active principle. Similarly, we showed that the (−)optical isomer of the “mixed” JH agonist/antagonist ethyl 4-[2-(t- butylcarbonyloxy) butoxy] benzoate (ETB) is the active principle of the racemic mixture. Injection or topical application of several intermediates of JH biosynthesis (mevalonlactone, homomevalonolactone or farnesoic acid) had little effect on resultant JH titer profiles in M. sexta larvae.

Anti-Juvenile Hormone Activity of Imidazole Compound (KK-22) and Its Diminution by Methoprene in the 4th Instar Silkworm, Bombyx mori L. : Lepidoptera : Bombycidae

1-Citronellyl-5-phenylimidazole (KK-22) was applied topically and orally to and mixed in the diets of 4th instar silkworm larvae, and its anti-juvenile hormone (JH) activity was determined by the induction rates of precocious metamorphosis. Larvae were more sensitive at the earlier stages of 4th instar to KK-22 and there were no significant differences in induction of precocious pupation among the administration methods, topical application, oral ingestion and feedng on diet. Anti-JH activity of KK-22 vanished when methoprene, a JH analogue, was applied immediately after KK-22 treatment.

Anti Juvenile Hormone Agents

The discovery and subsequent development of efficaceous juvenoids such as methoprene (Figure la) as functional mimics of the endogenous juvenile hormones (207; Figure lb. c) inspired thoughts that the reverse principle, anti juvenile hormone action, could be explored to complement the use of ju­ venoids. Such chemicals could be useful for those circumstances in which the continuation of some larval damage after treatment is not acceptable. This is the case in most field crop situations, in which use of fast-acting neuroactive pesticides is still the standard way to control pests. Because precocious metamorphosis results from surgical ablation of the corpora aJlata, it was reasonable to speculate that if chemical antagonists could be found that would be as effective as the surgical procedure they would be useful as control agents, provided that other characteristics such as selectivity,

Anti Juvenile Hormone Agents

The discovery and subsequent development of efficaceous juvenoids such as methoprene (Figure la) as functional mimics of the endogenous juvenile hormones (207; Figure lb. c) inspired thoughts that the reverse principle, anti juvenile hormone action, could be explored to complement the use of ju­ venoids. Such chemicals could be useful for those circumstances in which the continuation of some larval damage after treatment is not acceptable. This is the case in most field crop situations, in which use of fast-acting neuroactive pesticides is still the standard way to control pests. Because precocious metamorphosis results from surgical ablation of the corpora aJlata, it was reasonable to speculate that if chemical antagonists could be found that would be as effective as the surgical procedure they would be useful as control agents, provided that other characteristics such as selectivity,

Precocious Metamorphosis Induced by an Anti-Juvenile Hormone Compound Applied to 3rd Instar Silkworm Larvae, Bombyx mori L. (Lepidoptera : Bombycidae)

Induction of precocious metamorphosis in silkworm larvae, Bombyx mori by an anti-JH compound, 1-citronellyl-5-phenyl-midazole (KK-22), was investigated in relation to the application time of 3rd instar. Sensitive stage to KK-22 was in late 3rd instar. Most of the precocious pupation was observed in the 4th (penultimate) instar. Successive application with KK-22 prevented the 3rd instar larvae from molting into the next 4th instar and finally induced them to precocious pupation within the same 3rd (antepenultimate) instar. Some relationships were observed among the induction of precocious metamorphosis, the prolongation of 3rd instar, and the increase in body weight of 3rd instar larvae at molting. Most 3rd instar larvae with feeding periods prolonged by 2 days or more and having 70% or more increased body weight at 3rd molting time experienced precocious pupation at the subsequent 4th instar.

Relationship between juvenile hormone and ecdysteroids in larval-pupal development of Trichoplusia ni (Lepidoptera: Noctuiidae)

The haemolymph ecdysteroid titre during the late last stadium of the cabbage looper moth, Trichoplusia ni, was monitored in the presence of experimentally altered juvenile hormone levels to test the hypothesis that the appearance of a prepupal burst of juvenile hormone enhances prothoracic gland activity. Two peaks of ecdysteroid activity were detected in the haemolymph of last-stadium larvae (55 ng/ml and 950 ng/ml) with 20-hydroxyecdysone the most prevalent ecdysteroid. Treatment of post-feeding late last-stadium larvae with juvenile hormone I or the juvenoids, methoprene or epofenonane, had no significant effect on the timing or character of pupation. Application of juvenile hormone I to neck-ligated late last-stadium larvae failed to restore peak ecdysteroid levels to those of unligated controls. Application of the anti-juvenile hormone compounds, fluoromevalonolactone or 3,3-dichloro-2-propenyl hexanoate, disrupted metamorphosis causing delays in tanning and the formation of abnormal pupae. Yet, corresponding deviations in the timing or magnitude of ecdysteroid levels or in the conversion of ecdysone to 20-hydroxyecdysone were not observed. When early last-stadium larvae were treated with the juvenile hormone esterase inhibitor, 3-octylthio-1,1,1-trifluoro-2-propanone, shifts in the timing of peak ecdysteroid levels, coincident with delayed pupation, were observed. These results suggest that the prepupal prothoracic glands of T. ni may be considerably less sensitive to changes in the endogenous juvenile hormone titre by the time larvae have begun to wander, even though treatment at this time may still produce toxic effects that influence the success of ecdysis and/or resultant pupal morphology.

Anti-juvenile hormone effects of an imidazole compound (KK-42) in different larval instars of Bombyx mori.

Anti-juvenile hormone effects of an imidazole compound (KK-42) in different larval instars of Bombyx mori.

The effect of 2,2-dimethylchromene derivatives and some other compounds on the development ofOncopeltus fasciatus(dallas) andLocusta migratoria migratorioides(R&F)

As an adjunct to biochemical studies on the action of juvenile hormone antagonists (‘antijuvenile hormones’), a study has been made of the effects on insect development of 71 compounds based on the 2,2-dimethylchromene structure, and 30 other compounds, including especially chemicals containing acetylenic and 1,3-benzodioxole (methylenedioxyphenyl) groups, that were expected to inhibit microsomal mixed function oxidases. The ageratochromenes, 7-methoxy-2,2-dimethylchromene and 6,7-dimethoxy-2,2-dimethylchromene (precocene I and precocene II, respectively), were used for comparison. With the jar deposit method used for Oncopeltus fasciatus, and the topical application method used for Locusta migratoria, only derivatives of 2,2-dimethylchromene and 2-(3-methylbut-2-enyl)phenol, the alkene double bonds of which were activated by an alkoxy group, exhibited characteristic antijuvenile hormone actions. In the whole life-cycle exposure test on O. fasciatus, a number of other compounds had non-specific effects on development, especially at the fifth instar. Some of the compounds, including certain derivatives of 2,2-dimethylchromene with ester side-chains, had juvenile hormone agonist actions. The scope for structural optimization for antijuvenile hormone action in the 2,2-dimethylchromene series appears to be limited, and structure-activity relationships are obscured, especially for O. fasciatus, by an overlap between the prothetelic morphogenetic and lethal effects. The results are discussed in relation to the mode of action of the 2,2-dimethychromenes.

Synthesis and Anti-juvenile Hormone Activity of 2,2-Dimethyl-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.