Juvenoid activity

The compound should demonstrate the ability to mimic JH at the three principle stages of insect development the eggs, the juvenile and the adult (female). Therefore, observation of ovicidal effects is suggestive of juvenoid activity but not definitive. 

Table 3. Juvenoid Activity of Structurally-Related Juvabione Compounds...

Bakuchiol is a phenolic monoterpene (meroterpenoid) isolated from the seeds of Psoralea corylifolia L. (Fig. (6)) [107]. Topical application of 10 p.g of bakuchiol to fifth instar nymphs of D. koenigii, results in the metamorphosis to nymph-adult intermediates [108], This juvenoid activity is comparable to juvabione where application of 0.6 pg to fifth instars of P. apterus or 10 pg to last instar larvae of O. fasciatus, produced morphological abnormalities in 50% of the adults [91, 92]. The chemical data for bakuchiol is compiled in Appendix III, Table 11 and synthesis of the racemate methyl ether from geraniol has been reported [113]. 

Root extracts of the American coneflower, Echinacea augustifolia DC., also exhibited juvenoid activity [114] ether extracts showed high morphogenic activity on T. molitor pupae but none was observed on fifth instar nymphs of O. fasciatus (500 ig of extract). The active principle in the oil was identified as ( )-10-hydroxy-4,10-dimethy 1-4,11-dodecadien-2-one or echinolone (Fig. (6)) [109]. However, chemically synthesized echinolone was not active in the standard T. molitor pupal bioassay [115]. The authors of this report acknowledge that this may be due to a failure to synthesize the proper compound. However, the spectral data is consistent with that reported. They were also unable to isolate echinolone from the roots of E. augustifolia. The chemical data for echinolone are summarized in Appendix III, Table 12 and the synthesis of racemic echinolone has been reported [115, 116]. 

Other phytochemicals which exhibit JH activity include juvadecene (1-(3,4-methylenedioxyphenyI)-fraws-3-decene) isolated from roots of the pepper-tree, Macropiper excelsum Miq. [110], thujic acid (5,5-dimethyl-1,3,6-cycloheptatrien-l-carboxylic acid) extracted from the heartwood of western red cedar, Thujaplicata [111] andtagetone((E)-2,6-dimethyl-5,7-octadien-4-one) from the marigold, Tagetes minuta L. [112], There have been numerous reports of juvenoid activity of plant extracts (Table 5) however, to our knowledge, the compound(s) responsible for this activity have not been isolated and characterized. 

Since juvenoids affect the insect specific endocrine system, they are expected to become insect-specific insecticides [2]. Some naturally occurring compounds have juvenoid activity, e.g., Schmialek [3] isolated farnesol (1) and farnesal (2) with juvenoid activity from the feces of mealworm, Tenehrio molitor, (Fig. 25.2.1). 

Wigglesworth [4] confirmed that farnesol and its related compounds showed the juvenoid activity against the bloodsucking bug, Rhodnius prolixus. Slama and Williams [5] found that paper products made from balsam fir, Abies halsamea, showed juvenoid activity against hemipteran bug, Pyrrhocoris apterus, and called the compound the paper factor. The chemical structure of the paper factor was identified as a methyl ester of todomatuic acid, and named juvabione (3) [6]. 

Although many compounds with juvenoid activity have been found in plants, they are not practical insecticides due to chemical instability and complexity of synthesis. Many compounds have been synthesized and their activities were checked against insects to find more active and stable compounds. The following describes representative juvenoids reported so far. 

Bowers [7] found that some compounds used as insecticide synergists (e.g., piper-onyl butoxide) possess juvenoid activity, and so he synthesized analogues of the synergists, e.g., some aromatic terpenoid ether compounds, and examined their morphogenetic activity against T. molitor and milkweed bug, Oncopeltus fasciatus. He found the first synthetic compound (4, Fig. 25.2.2) with high activity [8]. 

Later, many compounds that introduced various substituents into the phenyl ring and/or changed the side chain were produced, among which 4-ethylphenyl ether 5 was found to have high juvenoid activity [9]. 

In contrast, researchers at Zoecon Corporation found high juvenoid activity in alkyl (2 ,4 )-3,7,ll-trimethyl-2,4-dodecadienoates, some of which were commercialized as methoprene (6, ZR-515) [10], kinoprene (7, ZR-777) [11], and hydro-prene (8, ZR-512) [10]. Since these compounds, however, possess double bonds and an ester bond in the molecule, they could not be used in the open field where stability in sunlight is required. 

Kokate CK, D Cruz JL, Kumar RA, Apte SS (1985) Anti-insect and juvenoidal activity of phytochemicals derived from Adhatoda vasica Nees. Ind J Nat Prod 1 7-9 Hassalani A, Lwande W (1989) Anti pest secondary metabolites from African plants. In Amason JT, Philogene BJR, Morand P (eds) Insecticides of plant origin. Am Chem Soc Symp series 387 78-94... 

Second-generation juvenoids incorporate more substantial stmctural departures from neotenin and are more resistant to metaboHc and environmental degradation. Epiphenonane, 2-ethyl-3-[3-ethyl-5-(4-ethylphenoxy)-pent-3-en-yl] 2-methyloxirane (131), has a rat oral LD q of 4000 mg/kg. It and similar juvenoids are used in China and Japan to prolong the last larval instar of the silkworm so that silk production is increased 10—15%. Fenoxycarb, ethyl [2-(4-phenoxyphenoxy)ethyl] carbamate (132) (mp 53°C, vp 0.0078 mPa at 20°C), is soluble in water to 6 mg/L. The rat oral LD q is >16,800 mg/kg. Fenoxycarb has a wide spectmm of activity, interfering with the developmental processes of fleas, cockroaches, and ants. 

Many papers from the patent literature on pyrethroids and juvenile hormones cannot be included in this Report. Papers have reported the synthesis and activity of monoterpenoid juvenoids, including geranyl pyridyl ethers " and geranyl alkyl ethers and amines and their epoxides. Further papers in this section include a report of the potent lung toxicity of perillaketone, the observation that the malodorous water contaminant 2-methylisoborneol has the l-R-exo configuration, and that fenchyl methyl L-aspartylaminomalonate is 2 x 10" times sweeter than sucrose. ... 

To study the relative intrinsic activity of a series of dienoate juvenoids, a forced feeding test was selected in which the materials were incorporated in the only food available to Blattella germanica populations throughout the duration of the experiment. This choice was made because of the difficulty in synchronizing the peak of sensitivity in the last nymphal instar due to the long... 

Hydroprene has proven to be the juvenoid of choice for the control of the major domestic cockroach species. Its success appears to be due to its very high intrinsic activity as compared with most other juvenoids and probably also to its volatility which may allow for a penetration of vapor in inaccessible cockroach harborages. It is likely that hydroprene vapors readily translocate between many household surface materials and thus remain accessible to resident cockroach populations. This volatility of hydroprene could also be a liability for persistence in places with high air displacement. In this case, hydroprene formulated for slow release in a dust (RF 10%) could provide a very persistent residue, albeit without the vapor benefits. 

We have been unable to interpret Edwards1 finding that exposure to earlier larval instars intensifies the response to methoprene (28). Other authors, working with more active juvenoids usually reported increasing sensitivity during the last nymphal instars (10). Since methoprene is only marginally active at 1000 ppm and mortality was prevalent in Edwards treatments, a confirmation is much needed. It is very obvious that more research into the nature of the infertility induced by juvenoids in general is much overdue. 

Does the AJH block the juvenoid induced increase in JHE activity Treatment L5D3 (9 AM) larvae selected doses of the AJH (100 nmol./larva is a good starting place) are coapplied with the juvenoid, epofenonane (100 nmol./larva). 

At this high dose only JH like activity may be seen. For example, it has been demonstrated that ETB can antagonize the JH action of the juvenoid epofenonane in ni (26, Figure 1) and yet be... 

Based on the above discussion, trifluoromethyl ketones should inhibit proteases such as chymotrypsin (32), and serine esterases, such as acetylcholinesterase (33,24)> carboxylesterases (10), JHE and other esterases with varying selectivity. In a series of some juvenoid-like trifluoromethyl ketones and compounds of the structure A, l,l,l-trifluoro-2-tetradecanone (TFT) was found to be highly active and selective against JHE (I50 lxlO 7M) as compared to a-naphthyl acetate esterase (o-NaE) or trypsin (4iJ>). 

Active compounds have been obtained by Henrick et al. (1978a) who incorporated a cyclopentene ring into the juvenoid skeleton (29). 

Pallos et al. (1974 1976) found compounds of strong morphogenetic action in the group of the bisthiolcarbamates, representing further departure from the terpenoid skeleton. They suggested, on the basis of the structural features of known juvenoids, a generalised molecular model for activity. The structure of the proposed template is... 

Williams and Kafatos (1971) and Karlson (1971) assume, in good agreement with their experimental results, that juvenoids act by specific changes in gene activation, thus interfering into developmental programmes. 

According to Minks (1967), juvenoids stimulate the Na/K pump, inducing a decrease in intracellular Na and an increase in intracellular K. This results in a stimulation of phosphorylation through a decrease of ATPase activity. On the... 

It cannot be decided on the basis of experimental results available so far whether the action of the synthetic juvenoids is a hormonomimetic effect exerted according to the same mechanism as that of endogenous juvenile hormones. The fact that compounds with a very different structure from that of natural juvenile hormones also display morphogenetic activity seems to suggest that at least an important part of synthetic juvenoids acts according to another mechanism. According to Bowers... 

Earlier attempts to develop compounds with anti-juvenile action remained unsuccessful. Slama et al. (1974) tested about 200compounds structurally related to juvenoids but lacking JH activity. None of them revealed anti-juvenile activity, in spite of the fact that they can be considered as potential antimetabolites of juvenile hormones. 

One defensive strategy of plants against insect herbivory is the production of secondary metabolites which mimic JH activity [3]. Many of these compounds have been extracted from diverse plant species and are termed "juvenoids" based on their activity in vitro. However, a number of criteria should be met before these compounds are defined as JH mimics ... 

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