Insect Juvenile Hormone Analogs Research Articles

Cascading effects caused by fenoxycarb in freshwater systems dominated by Daphnia carinata and Dolerocypris sinensis

To evaluate the aquatic hazards of the insect juvenile hormone analogue fenoxycarb, a single application (0, 48.8, 156.3, 500, 1600, and 5120 μg/L) of it was done in indoor freshwater systems dominated by Daphnia carinata (daphnid) and Dolerocypris sinensis (ostracoda). The responses of zooplankton (counted by abundance and the activity and immuno-reactive content of free N-Acetyl-β-D-glucosaminidase (NAGase)), phytoplankton (counted by chlorophyll and phycocyanin), planktonic bacteria and fungi, and some water quality parameters were investigated in a period of 35 d. Results of the study showed that the ostracoda was more sensitive than daphnid, with time-weighted average (TWA)-based no observed effect concentrations (NOECs) to be 8.45 and 12.66 μg/L in systems without humic acid addition (HA−) and to be 6.37 and 9.54 μg/L in systems with humic acid addition (HA+). The duration of treatment-related effects in the ostracoda population was longer than the daphnid population (21 vs. 14 days). Besides, the data analysis indicated that the toxicity of fenoxycarb was significantly enhanced in the HA+ systems. Owing to the reduced grazing pressure, the concentrations of chlorophyll and phycocyanin increased in the two highest treatments. The increase in photosynthesis along with a reduced animal excretion led to an increase in pH and a decrease in nutrient contents. These changes seemed to have an effect on the microbial communities. For example, the abundances of some opportunistic pathogens of aquatic animals (e.g. Aeromonas and Cladosporium) and organic-pollutant-degrading microorganisms (e.g. Ancylobacter and Azospirillum) increased significantly in microbial communities, but the abundances of Pedobacter, Candidatus Planktoluna, and Rhodobacter (photosynthetic bacteria) markedly decreased. This study provides useful information to understand the ecotoxicological impacts of fenoxycarb at the population and community levels while integrating the effects of HA on toxicity.

Insect hormones: more than 50-years after the discovery of insect juvenile hormone analogues (JHA, juvenoids)

Insect hormones: more than 50-years after the discovery of insect juvenile hormone analogues (JHA, juvenoids)

Steroid conjugates: Synthesis and preliminary biological testing of pro-juvenoids

A series of 10 new pro-juvenoids (juvenogens, insect hormonogenic compounds, pro-drug-like agents) was synthesized using isomeric synthetic juvenoids (insect juvenile hormone analogs) and steroid molecules as patterns modifying parts of the complex hormonogenic molecules. In addition, several new synthons were prepared, which were required by the designed synthetic protocol to achieve the target molecules. These pro-juvenoids were subjected to the topical screening tests and to the drinking assays on the red firebug ( Pyrrhocoris apterus), a convenient model laboratory phytophagous insect. Simple and efficient synthetic procedures for the preparation of the target pro-juvenoids and their synthons are presented. Furthermore, the biological activity of the pro-juvenoids in comparison with the activity of their parent juvenoids and that of several commercially available agents is demonstrated. Juvenoids and pro-juvenoids may replace toxic insecticides persistent in the insect pest control because they have no adverse effects on non-target organisms and/or human.

Novel Juvenogens (Insect Hormonogenic Agents): Preparation and Biological Tests on Neobellieria bullata

The development of new types of environmentally safe insecticides has been advantageous to replace toxic and persistent insecticides, which have adverse effects on animals and humans. Our effort in this field was aimed at the synthesis of insect juvenile hormone analogues, juvenoids, nontoxic for warm-blooded animals and fish, which can become advanced compounds in regulating many aspects in insect physiology. Structure modification of juvenoids via juvenogen derivatives (hormonogenic substances) plays an important role in controlling the juvenoid liberation rate in the insect digestive system and can also play an important role in the mode of action toward different arthropod groups, with focus on insect pest species. For that reason, juvenoids were esterified with hexadecanoic, butanoic, and 3-methylbut-2-enoic acids. A total of 12 new compounds with potential insecticidal activity were synthesized and characterized, and the results of biological screening tests on blowflies Neobellieria (Sarcophaga) bullata were presented. Results of the inhibitory activity of the tested compounds on the reproduction of the blowflies were also presented.

Effect of an insect juvenile hormone analogue, Fenoxycarb ® on development and oxygen uptake by larval lobsters Homarus gammarus (L.)

Little attention has been focused on the effect of anthropogenic compounds that disrupt the endocrine systems in crustaceans. Consequently, this study investigated the effects of the juvenile hormone analogue (JHA), Fenoxycarb ® on selected physiological and developmental processes of the zoeal stages in the European lobster, Homarus gammarus. Chronic exposure to Fenoxycarb (50μg L − 1) resulted in a significant ( p < 0.05) reduction in moult frequency and size at moult. Fenoxycarb exposure extended zoeal duration between zoea I to II ( p < 0.05) and resulted in total inhibition of the moult from zoea II to III. Significantly greater rates of O 2 uptake were observed in Fenoxycarb-exposed larvae in comparison with controls ( p < 0.05). All rates of O 2 uptake decreased significantly between 7 and 12d of exposure ( p < 0.05). At 12d, exposure to the solvent control no longer influenced rates of O 2 uptake, but it was not possible to attribute increased O 2 uptake to Fenoxycarb exposure directly, as treated individuals did not moult beyond zoea III. The low exposure concentrations of Fenoxycarb, comparable to those used in plant protection, resulted in endocrine disrupted responses in H. gammarus (albeit with little clear, demonstrable effect on metabolism) a finding that could have important ecological and commercial implications.

Characteristic Expression of Three Heat Shock-Responsive Genes During Larval Diapause in the Bamboo Borer Omphisa fuscidentalis

Three heat shock-responsive genes, Ofhsp70, Ofhsc70, and Ofhsp90, were identified in Omphisa fuscidentalis. These genes encode proteins with molecular weights of 70, 72, and 82 kDa, respectively, and were upregulated during heat shock. Ofhsp70 was expressed actively in the pre-diapause period, but its expression was low during diapause. While Ofhsc70 expression was low during pre-diapause and the first half of diapause, its expression increased greatly in the second half before diapause termination. In contrast, Ofhsp90 expression decreased by half during the transition to diapause and conspicuously decreased during late diapause. The results suggest that Ofhsp90 is associated with the maintenance of diapause and Ofhsc70 with the termination of diapause, whereas the expression of Ofhsp70 is unrelated to diapause. The insect molting hormone 20-hydroxyecdysone (20E) and juvenile hormone analog (JHA) caused increases in the mRNA expression of Ofhsc70, but not Ofhsp70 or Ofhsp90, in diapausing larvae. These transcriptional responses to 20E are consistent with the changes in ecdysteroid titer in the hemolymph relative to gene expression during diapause.

Testosterone and energy metabolism in the estuarine mysid Neomysis integer (Crustacea: Mysidacea) following exposure to endocrine disruptors.

A diverse set of reference compounds suspected of having an endocrine-disrupting mode of action (i.e., testosterone, flutamide, ethinylestradiol, precocene, nonylphenol, fenoxycarb, and methoprene) were tested for acute toxicity to the estuarine mysid Neomysis integer (Crustacea: Mysidacea). Neomysis integer was very sensitive to all tested compounds, with 96-h median lethal concentrations in a narrow range between 0.32 and 1.95 mg/L. The pesticides methoprene and fenoxycarb, both synthetic insect juvenile hormone analogs, were most toxic to N. integer. In addition, the short-term sublethal effects of methoprene and nonylphenol (an estrogen agonist) on the energy and steroid metabolism of N. integer were evaluated. Both compounds significantly affected energy and testosterone metabolism of N. integer at concentrations below acute toxicity levels. Energy consumption in methoprene- and nonylphenol-exposed mysids was significantly induced at 100 microg/L, resulting in a lower cellular energy allocation in these animals. Testosterone phase I metabolism was affected at 10 microg/L, whereas glycosylation was the most important phase II pathway affected in mysids exposed to 100 microg/L of both compounds. Methoprene exposure resulted in a concentration-dependent increase in the metabolic androgenization ratio. Mysids exposed to nonylphenol at 10 microg/L had a significantly higher metabolic androgenization ratio. The present study indicates that energy and testosterone metabolism of mysids, as endpoints, are able to detect endocrine-disruptive activity of chemicals after short-term exposure to environmentally realistic levels of endocrine disruptors.

Cytotoxic effects of two antimolting insecticides in mammalian CHO-K1 cells

Cytotoxicity of two insect growth regulators, diflubenzuron, a benzoylphenylurea derivative that inhibits the synthesis of new chitin in target organisms, and pyriproxyfen, an insect juvenile hormone analogue, were tested on CHO-K1 cultures, using the neutral red incorporation assay. Both compounds displayed cytotoxic effects that rise with time exposure. The presence of either fetal calf serum or bovine serum albumin diminished significantly the cytotoxicity of both compounds, thus pointing to a strong protein binding. In addition, extensive metabolization with rat liver submitochondrial fraction gave rise to metabolites less toxic than the parent compounds, implying the relative safety of both diflubenzuron and pyriproxyfen in mammals.

Foreign insect hormones stimulating the transcription of the ie-1 promoter of Bombyx mori nuclear polyhedrosis virus in vivo and in vitro.

Via a transient expression assay system, an experimental study was undertaken to characterize the effects of insect ecdysone and juvenile hormone analogue on the transient expression of the luciferase gene under the control of the immediate-early gene (ie-1) promoter of Bombyx mori nuclear polyhedrosis virus. The results demonstrated that the transcriptional activity of the ie-1 promoter was increased to a certain extent by different insect hormone treatments in uninfected insect cells or fifth instar silkworm larvae transfected with a plasmid containing a luciferase gene driven by the ie-1 promoter. By ecdysone treatment alone, an increase of 5-7 fold was reached in Bm-N, or Bm-5 cells, or in the early developmental stage of fifth instar larvae. By treatment with juvenile hormone analogue alone, about 2-fold, in Bm-N, Bm-5, and Sf-21 cells, or about 5-fold increase in the middle developmental stage of larvae was given, respectively. By co-treatment with ecdysone and juvenile hormone analogue, the incease was given between that of ecdysone and juvenile hormone analogue treatment alone. In addition, the synergistic effects of foreign/endogenous hormones on the activity of ie-1 promoter are discussed.

Regeneration of limbs and sensory organs in Ixodid ticks (Acari, Ixodeidea, Ixodidae and Argasidae)

We present a review of our own and literature data on reparative regeneration in ixodid ticks (chelicerate arthropods). Ticks have a high potential for reparative regeneration and a close relationship between regeneration and development determined by similar hormonal regulatory mechanisms. These mechanisms depend on ecdysteroid hormones, which participate in the initiation of both processes, and juvenile hormones, which direct these processes either to the maintenance of larval features or to the development of nymphal and adult features. We present a detailed analysis of the regeneration of Haller's sensory organs in ixodid ticks and propose an hypothesis about the role of juvenile hormones in the modification of morphogenetic processes in this group. Furthermore, we present data on the effects of insect juvenile hormone analogs (methoprene and fenoxycarb) on the regeneration of Haller's organ, which support this hypothesis. Studies on reparative regeneration in arthropods provide a broader view of the problem of repair morphogenesis in animals.

A comparison of the enantioselective reduction potential of five strains of Saccharomyces cerevisiae towards a selected ketone

The enantioselectivity potential of five strains of Saccharomyces cerevisiae was studied for the reduction of ethyl N-{2-{4-[(2-oxocyclohexyl)methyl]phenoxy}ethyl} carbamate (1), an insect juvenile hormone bioanalog. The products of the reaction, the cis and trans isomers of ethyl N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl} carbamate (2 and 3), were obtained in 45–49% (w/w) chemical yields and with 79 to > 99% enantiomeric purity values. The absolute configurations of the major products were assigned as ethyl (1S,2S)-N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl} carbamate (2) and ethyl (1S,2R)-N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl} carbamate (3). The products 2 and 3 belong to the series of the chiral insect juvenile hormone analogs.

Growth, lipid class and fatty acid composition in juvenile mud crabs (Rhithropanopeus harrisii ) following larval exposure to Fenoxycarb, insect juvenile hormone analog.

This study examines the effects of Fenoxycarb on larval growth, and lipid class and fatty acid composition in first crabs of the mud crab Rhithropanopeus harrisii reared through total larval development in nominal water concentrations from 1 to 100 microg/l. In first crabs of R. harrisii, dry weight (microg) decreased significantly (P < 0.05) from 228.8+/-38.2 microg (n = 9) in the controls to 131.8+/-10.1 microg (n = 4) in animals exposed throughout larval development to 100 microg/l. A significant (P < 0.05) reduction was found between total lipid content in the controls and first crabs reared at concentrations greater than 50 microg/l. In relative terms (% dry weight), different lipid classes predominated in the controls and the various fenoxycarb exposure concentrations. There were no significant (P > 0.05) differences among the treatment groups in phospholipid level, while the triglyceride content was significantly lower in crabs exposed to 10 and 100 microg/l. No significant differences in the percent of free fatty acids were found in crabs exposed to 1-10 microg/l and the controls. Free sterols in crabs exposed to concentrations higher than 10 microg/l were below the detection limit. Control animal fatty acid profiles were dominated by palmitic, stearic, and oleic acid, accounting for 48% of total fatty acids (TFA). The fatty acid composition of crabs exposed to 100 microg/l significantly (P < 0.05) differed from the controls. The results suggest that fenoxycarb has substantial effects on growth, lipid class and fatty acid composition in developing larvae of R. harrisii at water concentrations greater than 10 microg/l.

Effects of endocrine‐active chemicals on the development of sex characteristics of Daphnia magna

AbstractStandard reproductive assays with daphnids involve parthenogenetically reproducing females and exclude the assessment of effects on sexual reproduction. The goals of this study were to characterize sexual differentiation of male and female daphnids (Daphnia magna) and to evaluate whether exposure to putative endocrine‐disrupting chemicals may perturb the development of sex characteristics. Anatomical sex differences that developed during maturation in males included elongated first antennae and morphologic alterations in the head capsule and carapace edge. Reproductive maturation in females was associated with the development of a brood chamber and abdominal process. Alterations in the growth rates of the first antennae of males and the abdominal process of females were used to evaluate the effects of chemical exposure on the development of these sex characteristics during maturation. Exposure of female daphnids to the nonsteroidal vertebrate estrogen diethylstilbesterol and the insect juvenile hormone analog methoprene at concentrations as low as 3.0 and 0.080 μM, respectively, stimulated development of the abdominal process. Exposure of males to the steroidal vertebrate androgen androstenedione (≥6.0 μM) stimulated development of the first antennae. These results demonstrate that the development of secondary sex characteristics in daphnids can be altered by chemical exposure.

A Study of the Metabolic Degradation of an insect juvenile hormone analog using different radiolabeling

AbstractThe fate of an insect juvenile hormone analog applied to the insect body of the flesh fly (Sarcophaga bullata) or the tsetse fly (Glossina palpalis), respectively, was studied using three different radiolabeled positions in the parent biologically active compound 1. Several metabolites were found and analyzed. A mechanism of degradation of the applied molecule was designed using a combination of several radioanalytical methods. A unique monitoring of the applied compound and its metabolites was provided, based on the different radiolabeling of the structure (cf. 1a–1c), and established their fate in an insect body during a 10‐day experiment. A 14C and 3H radiolabeling, respectively, was employed to synthesize three different radiolabeled forms 1a–1c derived from the parent non‐labeled 1. A combination of three different ways of radiolabeling resulted in an advantage in tracing the metabolic pathway of degradation of the employed compound 1 in its radiolabeled forms 1a–1c.

Degradation of a radiolabeled juvenile hormone analog using two insect species.

A synthetic insect juvenile hormone analog (a juvenoid), ethyl N-[2-[4-[[2,2-(ethylenedioxy)cyclohexyl]methyl]phenox]ethyl]carbam ate, which has displayed high biological activity against different insect species and high stability under field conditions, was selected as a biologically active model compound for a study of a juvenile hormone analog degradation. The biologically active compound itself and its three diversely radiolabeled derivatives were applied to the flesh fly (Sarcophaga bullata) or the tsetse fly (Glossina palpalis), respectively. Monitoring of a fate of the applied juvenile hormone analog was carried out using a detection method of the radioactivity microdistribution within the whole insect body in combination with a radio high performance liquid chromatography (radio-HPLC), both of whole-body extracts made in different, but in advance scheduled, time intervals, and of extracts of insect excreta accumulated over an eight-day experiment.

A Series of Bicyclic Insect Juvenile Hormone Analogs of Czech Origin: Twenty Years of Development

Research results are summarized from a series of insect juvenile hormone analogs derived from 2-(4-hydroxybenzyl)-1-cycloalkanones, which have been investigated at the Institute of Organic Chemistry and Biochemistry in Prague during the past 20 years. At present, practical application of several prospective structures for insect control is under investigation. Biological activity values were determined to delineate the most important subseries of compounds and the most promising insect juvenile hormone analogs selected from the subseries. Carbamates, and in particular compound 47 proved to be highly active against aphids, cockroaches, flies, and many other insect species.

Identification of in vitro release products of corpora allata in female and male loreyi leafworms,Leucania loreyi

The in vitro release of juvenile hormones (JH) by female, and of JH acids (JHA) by male corpora allata (CA) ofLeucania loreyi was identified by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Separation and quantification were accomplished by HPLC and GC, respectively. JH II and JH III were the major components released by CA of females. Four JHA analogues were identified as the release products of male CA, i.e. JHA III, Iso-JHA II, JHA II and JHA I. JHA III and Iso-JHA II were reported for the first time as the major release products of CA of adult male Lepidoptera. Iso-JHA II is a new member of the insect juvenile hormone analogue family.

Novel Juvenoids of the 2‐(4‐hydroxybenzyl)cyclohexan‐1‐one Series

AbstractA series of insect juvenile hormone analogs (juvenoids) was synthesized and studied. The basic skeleton of these juvenoids contains three rings and a short aliphatic subunit and bears two or three chiral centers (depending on the appropriate structure; see 6–9). The chiral center located in the 1,2‐diphenoxypropane subunit has the configuration (RS), (R) (a series), or (S) (b series). The juvenoids were subjected to a biological screening, the preliminary results of which are briefly described.

Elimination of a Population of the Oriental Cockroach (Dictyoptera: Blattidae) in a Simulated Domestic Environment with the Insect Juvenile Hormone Analogue (S)-Hydroprene

Two mixed (seminatural) populations of the Oriental cockroach, Blatta orientalis (L.), were established in identical artificial domestic environments contained inside converted steel freight containers. After a 10-wk period of acclimation, during which the populations were monitored with Roatel traps, one population was treated with an aerosol formulation (total release fogger) containing 290 mg of the juvenile hormone analogue (S)-hydroprene. The other (control) population was treated with aerosol propellant only. These treatments were repeated at approximately 6 monthly intervals for the duration of the experiment. Changes in these populations were monitored for a period of 28 mo by regular trapping with live-catch Roatel traps. On each occasion, trapped insects were counted, sexes were determined, nymphs were assigned to one of three arbitrary size categories (small, medium, or large), and adults were examined for external morphological deformities. At monthly intervals, 20 adult females also were randomly selected from the trapped insects and confined with several trapped males, and a record of ootheca production and viability was kept. During the first 6 mo of the experiment, both populations showed a general increase. Subsequently, the population in the control environment remained high for the duration of the experiment. In contrast, the population in the environment treated with hydroprene gradually declined and was eradicated after 26 mo. Elimination of the treated population resulted directly from the inhibition of reproduction in adult cockroaches that had been exposed to hydroprene during the latter stages of nymphal development. These results indicate that the juvenile hormone analogue (S)-hydroprene has considerable potential for use as a control agent against populations of Blatta orientalis infesting industrial, food manufacturing, and domestic premises.

Microbiological transformations. 30. Enantioselective hydrolysis of racemic epoxides: the synthesis of enantiopure insect juvenile hormone analogs (bower's compound)

The enantioselective epoxide biohydrolysis of the racemic benzodioxole 6,7-epoxygeraniol derivative 1 has been achieved using the fungus A. niger. This new type of preparative scale bioconversion allows the synthesis of both enantiomers of Bower's compound, an analogue of insect juvenile hormone. Biological tests showed that the 6(R) enantiomer was about ten times more active than the 6(S) enantiomer against the yellow meal worm Tenebrio molitor.