Synthesis and biological properties of aryl methyl sulfones.

A novel group of aryl methyl sulfones based on nonsteroidal anti-inflammatory compounds exhibiting a methyl sulfone instead of the acetic or propionic acid group was designed, synthesized and evaluated in vitro for inhibition against the human cyclooxygenase of COX-1 and COX-2 isoenzymes and in vivo for anti-inflammatory activity using the carrageenan induced rat paw edema model in rats. Also, in vitro chemosensitivity and in vivo analgesic and intestinal side effects were determined for defining the therapeutic and safety profile. Molecular modeling assisted the design of compounds and the interpretation of the experimental results. Biological assay results showed that methyl sulfone compounds 2 and 7 were the most potent COX inhibitors of this series and best than the corresponding carboxylic acids (methyl sulfone 2: IC50 COX-1 = 0.04 and COX-2 = 0.10 µM, and naproxen: IC50 COX-1 = 11.3 and COX-2 = 3.36 µM). Interestingly, the inhibitory activity of compound 2 represents a significant improvement compared to that of the parent carboxylic compound, naproxen. Further support to the results were gained by the docking studies which suggested the ability of compound 2 and 7 to bind into COX enzyme with low binding free energies. The improvement of the activity of some sulfones compared to the carboxylic analogues would be performed through a change of the binding mode or mechanism compared to the standard binding mode displayed by ibuprofen, as disclosed by molecular modeling studies. So, this study paves the way for further attention in investigating the participation of these new compounds in the pain inhibitory mechanisms. The most promising compounds 2 and 7 possess a therapeutical profile that enables their chemical scaffolds to be utilized for development of new NSAIDs.

Sexual communication in castniid moths: Males mark their territories and appear to bear all chemical burden.

Castniid moths (Lepidoptera: Castniidae) display a butterfly-like reproductive behavior, i.e., they use visual stimuli for mate location and females have apparently lost their pheromone glands in an evolutionary context. In this paper we report for the first time the identification of three new compounds, namely n-octadecyl acetate, (Z)-9-octadecenyl acetate and (E,Z)-2,13-octadecadienyl acetate, in males of the Castniid Palm Borer, Paysandisia archon, which could be involved in its short-range courtship behavior, and also shed light on recent controversies on the sexual behavior of the species. The compounds are produced in a ring-shaped gland of the male terminalia and have occasionally been detected in very minor amounts (ng) in ovipositor extracts of females, but only while mating or just after copulation. We also report that males use the already known (E,Z)-2,13-octadecadienol to mark their territory by rubbing their midlegs against the upper side of nearby leaves, especially palm leaves. This compound, produced in large amounts, is mostly concentrated in the midleg basitarsi and its maximum production is detected on the sexually mature 1-day-old specimens. In addition, analysis of male wings extracts confirms the presence of Z,E and E,E-farnesals, which are mostly produced in the median band of hindwings of 48-53 h-old insects. The biological significance of farnesals in this species is unknown. Our results point out that the chemical communication of P. archon relies mostly on males, which appear to bear all chemical burden in this respect.

Synthesis, Functional Assays, Electrophysiological Activity, and Field Tests of Pheromone Antagonists of the Tomato Leafminer, Tuta absoluta.

The tomato leafminer, Tuta absoluta, is one of the major pests of tomato and other Solanaceae in many regions worldwide. In the search for new strategies to control this pest, we present herewith the stereoselective synthesis, electrophysiological activity, functional analysis, and field tests of new chemicals as possible antagonists of the sex pheromone of the leafminer. The chemicals are methyl ketone (MK) and trifluoromethyl ketone (TFMK) structural analogues of both components of the pheromone. Most of the chemicals exerted per se some electrophysiological activity and inhibited the electroantennographic response to the pheromone when vapors of the inhibitor were passed over the antennae. Except TFMK 3, which elicited a modest effect, the compounds did not exhibit antiesterase activity on the pheromone-degrading enzymes of the antennae, but in the field the chemicals, particularly MK 5, notably decreased the number of catches when mixed with the pheromone in 1:1 and 10:1 ratios, regardless the infestation level of the plot. These results suggest that MK 5 is a good behavioral antagonist of the pheromone to be considered as a putative agent to control the pest in new future integrated pest management (IPM) strategies.

Field trapping of the flathead oak borer Coroebus undatus (Coleoptera: Buprestidae) with different traps and volatile lures.

The flathead oak borer Coroebus undatus F. (Coleoptera: Buprestidae) is one of the primary pests of cork oak Quercus suber L. in the Mediterranean region causing great economic losses to the cork industry. Very little is known about its biology and behavior and, so far, no control measures have been established. We present the results of a pilot study aimed to develop an efficient trapping method for monitoring this harmful pest. In a 3-year field study, purple-colored prism traps baited with a mixture of green leaf volatiles (GLVs) from the host have been shown the most effective combination to catch C. undatus adults (solely females) compared to other trap and lure types tested. Wavelength and reflectance measurements revealed that purple traps exhibit reflectance peak values similar to those found in the abdominal and elytral cuticle of both sexes, suggesting the involvement of visual cues for mate location in this species. The data presented are the first to demonstrate captures of adults of the genus Coroebus by an attractant-based trapping method.

Cuticular and internal chemical composition of biting midges Culicoides spp. (Diptera: Ceratopogonidae), potential vectors of viral diseases.

The chemical profile of the cuticle and internal tissues of four species of Culicoides have been studied for the first time by gas chromatography-mass spectrometry. The chemical composition of females of C. obsoletus s.l. and C. lupicaris, vectors of diverse viral diseases, have been compared with that of other biting midges, such as C. kibunensis and C. fascipennis, and the non-biting midge Forcipomyia bipunctata. A total of 61 compounds belonging to 8 major chemical classes were identified in cuticular and internal tissues in n-hexane extracts. The compounds include carboxylic acids (CAs) (C6-C20), with C16:0, C16:1 and C18:1 being dominant, branched hydrocarbons (C29 to C38 mono/di/trimethylalkanes), linear hydrocarbons (C15 to C33, mainly odd chain carbons), terpenes (geranylacetone, geranylgeraniol acetate, squalene, terpenic alcohol), steroids (cholesterol), aldehydes (C9-C10 and even chain C20 to C30), and esters. The chemical profile depends on the species and whether the extracts are external (cuticle) or internal. The contents of linear and branched hydrocarbons and aldehydes was high in cuticular extracts but practically absent in internal tissues, which were, in contrast, rich in CAs, terpenes and steroids. The results are discussed and compared with other Culicoides midges and mosquito-related species.

Phytal: a candidate sex pheromone component of the moroccan locust dociostaurus maroccanus.

Outbreaks of locusts cause enormous economic losses to agriculture in many countries. To develop environmentally friendly strategies for their control, much research has been focused on the factors that influence locust biology, particularly infochemical-mediated interactions. We present herein the identification and synthesis of both Z and E isomers of phytal (3,7,11,15-tetramethylhexadec-2-enal, 1), which are involved in chemical communication and behaviour of the Moroccan locust, Dociostaurus maroccanus, a serious agricultural pest. The compound was identified by comparison of its chromatographic and spectrometric features and microchemical reactions with those of a synthetic sample. The natural compound was shown to have the R,R configuration by chiral HPLC analysis, and its structure is unique as an insect pheromone component. Both isomers of phytal are produced by sexually mature adult males and elicit electroantennographic responses in antennae of both sexes. In two-choice olfactometer bioassays, males and females significantly preferred the stream enriched with racemic phytal to the control. In contrast, hydrogenated phytal was behaviourally inert. Both isomers of phytal are specific to D. maroccanus as they are absent in the closely related, habitat-sharing species Dociostaurus jagoi and Calliptamus wattenwylianus. Legs and wings are the main release sites of the compound: approximately 90 % of that emitted by living individuals. In biosynthetic studies, phytal appears to proceed from oxidation of phytol (2) after injection of deuterated phytol into the abdomen of the insect or after administration in the diet. Our results demonstrate that phytal is a candidate sex pheromone component of the Moroccan locust; it is produced by mature males, and might be eavesdropped upon by conspecific males.

Electrophilic derivatives antagonise pheromone attraction in Cydia pomonella.

BACKGROUND: Pheromone antagonists are good disruptants of the pheromone communication in insects and, as such, have been used in mating disruption experiments. In this study, new non-fluorinated electrophilic keto derivatives structurally related to the pheromone of Cydia pomonella (codlemone) have been synthesised and tested as putative pheromone antagonists. RESULTS: Codlemone (1) was prepared in excellent stereoselectivity in a new, iterative approach involving two Horner-Wadsworth-Emmons reactions. Methyl ketone (2), keto ester (3) and diketone (4) were obtained from codlemone in straightforward approaches in good overall yields and excellent stereochemical purity (≥98% E,E). In electrophysiology, only compound 2 displayed inhibition of the antennal response to the pheromone after presaturation of the antennal receptors. Compounds 2 to 4 did not inhibit the pheromone-degrading enzyme responsible for codlemone metabolism, but mixtures of ketone 2 and diketone 4 with codlemone elicited erratic flights on males in a wind tunnel. In the field, blends of either compound (2 or 4) with the pheromone caught significantly fewer males than codlemone alone. CONCLUSION: Codlemone and the potential antagonists 2 to 4 have been synthesised in good yields and excellent stereoselectivity. These chemicals behave as pheromone antagonists of the codling moth both in the laboratory and in the field.

A carboxylesterase, Esterase-6, modulates sensory physiological and behavioral response dynamics to pheromone in Drosophila.

BACKGROUND: Insects respond to the spatial and temporal dynamics of a pheromone plume, which implies not only a strong response to 'odor on', but also to 'odor off'. This requires mechanisms geared toward a fast signal termination. Several mechanisms may contribute to signal termination, among which odorant-degrading enzymes. These enzymes putatively play a role in signal dynamics by a rapid inactivation of odorants in the vicinity of the sensory receptors, although direct in vivo experimental evidences are lacking. Here we verified the role of an extracellular carboxylesterase, esterase-6 (Est-6), in the sensory physiological and behavioral dynamics of Drosophila melanogaster response to its pheromone, cis-vaccenyl acetate (cVA). Est-6 was previously linked to post-mating effects in the reproductive system of females. As Est-6 is also known to hydrolyze cVA in vitro and is expressed in the main olfactory organ, the antenna, we tested here its role in olfaction as a putative odorant-degrading enzyme. RESULTS: We first confirm that Est-6 is highly expressed in olfactory sensilla, including cVA-sensitive sensilla, and we show that expression is likely associated with non-neuronal cells. Our electrophysiological approaches show that the dynamics of olfactory receptor neuron (ORN) responses is strongly influenced by Est-6, as in Est-6° null mutants (lacking the Est-6 gene) cVA-sensitive ORN showed increased firing rate and prolonged activity in response to cVA. Est-6° mutant males had a lower threshold of behavioral response to cVA, as revealed by the analysis of two cVA-induced behaviors. In particular, mutant males exhibited a strong decrease of male-male courtship, in association with a delay in courtship initiation. CONCLUSIONS: Our study presents evidence that Est-6 plays a role in the physiological and behavioral dynamics of sex pheromone response in Drosophila males and supports a role of Est-6 as an odorant-degrading enzyme (ODE) in male antennae. Our results also expand the role of Est-6 in Drosophila biology, from reproduction to olfaction, and highlight the role of ODEs in insect olfaction.

Electrophysiological and behavioral responses of the black-banded oak borer, Coroebus florentinus, to conspecific and host-plant volatiles.

Aspects of the chemical ecology of the black-banded oak borer, (BBOB) Coroebus florentinus (Coleoptera: Buprestidae), were studied. Odors produced by males and females were similar, both qualitatively and quantitatively. Nonanal, decanal, and geranylacetone, identified in the headspace of both sexes, elicited strong electroantennographic responses from male antennae, but not from female antennae. In dual-choice olfactometer experiments, a blend of these three compounds was attractive to both sexes; males responded to decanal alone, while females responded to geranylacetone alone, suggesting that these compounds are responsible for activity of the blend to the respective sexes. Antennae of both sexes responded electroantennographically to the green leaf volatiles (E)-2-hexenal, (E)-2-hexenol, 1-hexanol, (Z)-3-hexenyl acetate, and n-hexyl acetate, all identified from the host plant Quercus suber. In behavioral experiments, only females were attracted to host-plant odors, and in tests with synthetic compounds, females were attracted to (E)-2-hexenol, 1-hexanol, and (Z)-3-hexenyl acetate. It is likely that these compounds play a role in foraging and/or oviposition behavior of BBOB females.

Moths behaving like butterflies. Evolutionary loss of long range attractant pheromones in castniid moths: a Paysandisia archon model.

BACKGROUND: In the course of evolution butterflies and moths developed two different reproductive behaviors. Whereas butterflies rely on visual stimuli for mate location, moths use the 'female calling plus male seduction' system, in which females release long-range sex pheromones to attract conspecific males. There are few exceptions from this pattern but in all cases known female moths possess sex pheromone glands which apparently have been lost in female butterflies. In the day-flying moth family Castniidae ("butterfly-moths"), which includes some important crop pests, no pheromones have been found so far. METHODOLOGY/PRINCIPAL FINDINGS: Using a multidisciplinary approach we described the steps involved in the courtship of P. archon, showing that visual cues are the only ones used for mate location; showed that the morphology and fine structure of the antennae of this moth are strikingly similar to those of butterflies, with male sensilla apparently not suited to detect female-released long range pheromones; showed that its females lack pheromone-producing glands, and identified three compounds as putative male sex pheromone (MSP) components of P. archon, released from the proximal halves of male forewings and hindwings. CONCLUSIONS/SIGNIFICANCE: This study provides evidence for the first time in Lepidoptera that females of a moth do not produce any pheromone to attract males, and that mate location is achieved only visually by patrolling males, which may release a pheromone at short distance, putatively a mixture of Z,E-farnesal, E,E-farnesal, and (E,Z)-2,13-octadecadienol. The outlined behavior, long thought to be unique to butterflies, is likely to be widespread in Castniidae implying a novel, unparalleled butterfly-like reproductive behavior in moths. This will also have practical implications in applied entomology since it signifies that the monitoring/control of castniid pests should not be based on the use of female-produced pheromones, as it is usually done in many moths.

Enzymatic enantiomeric resolution of phenylethylamines structurally related to amphetamine.

Both enantiomers of several phenylethylamines, structurally related to amphetamine, have been prepared in good yields and excellent enantiomeric purity by enzymatic kinetic resolution using CAL-B and ethyl methoxyacetate as the acyl donor. In the case of the 4-hydroxyderivative of amphetamine (compound 4i), the S enantiomer racemized possibly in a dynamic kinetic resolution (DKR) under the enzymatic conditions used.

Synthesis of allylic trifluoromethyl ketones and their activity as inhibitors of the sex pheromone of the leopard moth, Zeuzera pyrina L. (Lepidoptera: Cossidae).

BACKGROUND: Trifluoromethyl ketones (TFMKs), structurally related to the pheromones, are good inhibitors of pheromone communication in insects. To determine their activity on Zeuzera pyrina L. (Lepidoptera: Cossidae), a polyphagous pest, the authors have prepared two diunsaturated TFMK analogues of the major (3) and the minor (4) pheromone components, and two monounsaturated ones (5, 6). Their biological activity in electroantennogram (EAG), wind tunnel and field tests is presented. RESULTS: The synthetic strategy to obtain the allylic TFMKs 3 and 5 is based on the reactions of diene 10 and 1-octadecene with trifluoroacetaldehyde ethyl hemiacetal, followed by Dess-Martin oxidation of the resulting homoallylic trifluoromethyl alcohols. In EAG, topical application of analogues 3 and 4 on male antennae significantly reduced the pheromone response. In the wind tunnel, compound 4 reduced the number of contacts with the pheromone source. In the field, traps baited with mixtures of pheromone and inhibitors captured significantly fewer males than the pheromone alone. CONCLUSION: An efficient synthesis of allylic TFMKs is reported, with good overall yield, regiospecificity and diastereoselectivity. These compounds are good inhibitors of the pheromone in electrophysiology, wind tunnel and field tests. The results show the importance of two unsaturations at positions 2 and 13 of the trifluoroacyl group in the structure of the analogues, the latter being critical for inhibitory activity.

Degradation of pheromone and plant volatile components by a same odorant-degrading enzyme in the cotton leafworm, Spodoptera littoralis.

BACKGROUND: Odorant-Degrading Enzymes (ODEs) are supposed to be involved in the signal inactivation step within the olfactory sensilla of insects by quickly removing odorant molecules from the vicinity of the olfactory receptors. Only three ODEs have been both identified at the molecular level and functionally characterized: two were specialized in the degradation of pheromone compounds and the last one was shown to degrade a plant odorant. METHODOLOGY: Previous work has shown that the antennae of the cotton leafworm Spodoptera littoralis, a worldwide pest of agricultural crops, express numerous candidate ODEs. We focused on an esterase overexpressed in males antennae, namely SlCXE7. We studied its expression patterns and tested its catalytic properties towards three odorants, i.e. the two female sex pheromone components and a green leaf volatile emitted by host plants. CONCLUSION: SlCXE7 expression was concomitant during development with male responsiveness to odorants and during adult scotophase with the period of male most active sexual behaviour. Furthermore, SlCXE7 transcription could be induced by male exposure to the main pheromone component, suggesting a role of Pheromone-Degrading Enzyme. Interestingly, recombinant SlCXE7 was able to efficiently hydrolyze the pheromone compounds but also the plant volatile, with a higher affinity for the pheromone than for the plant compound. In male antennae, SlCXE7 expression was associated with both long and short sensilla, tuned to sex pheromones or plant odours, respectively. Our results thus suggested that a same ODE could have a dual function depending of it sensillar localisation. Within the pheromone-sensitive sensilla, SlCXE7 may play a role in pheromone signal termination and in reduction of odorant background noise, whereas it could be involved in plant odorant inactivation within the short sensilla.

Characterization of an antennal carboxylesterase from the pest moth Spodoptera littoralis degrading a host plant odorant.

BACKGROUND: Carboxyl/cholinesterases (CCEs) are highly diversified in insects. These enzymes have a broad range of proposed functions, in neuro/developmental processes, dietary detoxification, insecticide resistance or hormone/pheromone degradation. As few functional data are available on purified or recombinant CCEs, the physiological role of most of these enzymes is unknown. Concerning their role in olfaction, only two CCEs able to metabolize sex pheromones have been functionally characterized in insects. These enzymes are only expressed in the male antennae, and secreted into the lumen of the pheromone-sensitive sensilla. CCEs able to hydrolyze other odorants than sex pheromones, such as plant volatiles, have not been identified. METHODOLOGY: In Spodoptera littoralis, a major crop pest, a diversity of antennal CCEs has been previously identified. We have employed here a combination of molecular biology, biochemistry and electrophysiology approaches to functionally characterize an intracellular CCE, SlCXE10, whose predominant expression in the olfactory sensilla suggested a role in olfaction. A recombinant protein was produced using the baculovirus system and we tested its catabolic properties towards a plant volatile and the sex pheromone components. CONCLUSION: We showed that SlCXE10 could efficiently hydrolyze a green leaf volatile and to a lesser extent the sex pheromone components. The transcript level in male antennae was also strongly induced by exposure to this plant odorant. In antennae, SlCXE10 expression was associated with sensilla responding to the sex pheromones and to plant odours. These results suggest that a CCE-based intracellular metabolism of odorants could occur in insect antennae, in addition to the extracellular metabolism occurring within the sensillar lumen. This is the first functional characterization of an Odorant-Degrading Enzyme active towards a host plant volatile.

Synthesis, anti-inflammatory activity, and in vitro antitumor effect of a novel class of cyclooxygenase inhibitors: 4-(aryloyl)phenyl methyl sulfones.

Following our previous research on anti-inflammatory drugs (NSAIDs), we report on the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2) isoenzymes. Molecular modeling studies showed that the methylsulfone group of these compounds was inserted deep in the pocket of the human COX-2 binding site, in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355 through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of COX-2 and also the most selective (COX-1/COX-2 IC(50) ratio was 262). The indole derivative 33 was further tested in vivo for its anti-inflammatory activity in rats. This compound showed greater inhibitory activity than ibuprofen. Other compounds (20, 26, 9, and 30) showed strong activity against carrageenan-induced inflammation. The latter compounds showed a weak capacity to inhibit the proliferation of human cell lines K562, NCI-H460, and HT-29 in vitro.

Reactivity versus steric effects in fluorinated ketones as esterase inhibitors: a quantum mechanical and molecular dynamics study.

Carboxylesterases (CEs) are a family of ubiquitous enzymes with broad substrate specificity, and their inhibition may have important implications in pharmaceutical and agrochemical fields. One of the most potent inhibitors both for mammalian and insect CEs are trifluoromethyl ketones (TFMKs), but the mechanism of action of these chemicals is not completely understood. This study examines the balance between reactivity versus steric effects in modulating the activity against human carboxylesterase 1. The intrinsic reactivity of the ketone moiety is determined from quantum mechanical computations, which combine gas phase B3LYP calculations with hydration free energies estimated with the IEF/MST model. In addition, docking and molecular dynamics simulations are used to explore the binding mode of the inhibitors along the deep gorge that delineates the binding site. The results point out that the activity largely depends on the nature of the fluorinated ketone, since the activity is modulated by the balance between the intrinsic electrophilicity of the carbonyl carbon atom and the ratio between keto and hydrate forms. However, the results also suggest that the correct alignment of the alkyl chain in the binding site can exert a large influence on the inhibitory activity, as this effect seems to override the intrinsic reactivity features of the fluorinated ketone. Overall, the results sustain a subtle balance between reactivity and steric effects in modulating the inhibitory activity of TFMK inhibitors.

Sex pheromone of the Spanish population of the beet armyworm Spodoptera exigua.

The pheromone composition of the Spanish population of the beet armyworm (BAW), Spodoptera exigua (Lepidoptera: Noctuidae), was identified. Analysis of female gland extracts showed the presence of compounds Z9,E12-14:Ac (1), Z9-14:Ac (2), Z11-16:Ac (3), Z9,E12-14:OH (4), Z9-14:OH (5), and Z11-16:OH (6) in a ratio of 26:11:1:22:31:9. The amount of compound per gland ranged from 2.08 ng for 5 to 0.09 ng for 3. However, analysis of female volatiles by SPME revealed only the presence of compounds, 1, 2, 3, and 5 in a 34:40:4:22 ratio. In electroantennogram assays, compound 1 elicited the highest response, and the C14 acetates evoked higher electrophysiological responses than the corresponding alcohols or C16 isomers. In a wind tunnel, no behavioral difference was observed between formulations based on the gland extracts and female volatiles. In both cases, males responded as when virgin females were used as the attractant source. Compound 1 alone elicited upwind flight by males, but required the presence of compound 5 in a 80:20 to 40:60 ratio for full activity. Ternary mixtures of 1, 5 and the minor components did not improve the performance of the 1+5 blend in a 60:40 ratio. In the field, the mixture 1+5+3 in a 56:37:7 ratio was the most attractive formulation, and is expected to be useful in future pest control strategies.

Development and biological activity of a new antagonist of the pheromone of the codling moth Cydia pomonella.

A new pheromone antagonist of the codling moth Cydia pomonella is reported. Presaturation of the antennae of the insects with vapors of the antagonist (E,E)-8,10-dodecadienyl trifluoromethyl ketone, analogue of the main component of the pheromone (codlemone), resulted in lower electrophysiological responses to the pheromone relative to untreated insects. In the wind tunnel, the compound elicited a remarkable disruptive effect on all types of behavior of males flying toward a source baited with a pheromone/antagonist blend in 1:1, 1:5, and 1:10 ratios. The insects displayed erratic flights in the presence of the antagonist, as shown by their flight parameters in comparison to insects attracted to the pheromone alone. In the field, traps baited with mixtures of 1:10 codlemone/antagonist attracted considerably lower numbers of males than the natural attractant. The antagonist, however, did not inhibit the pheromone-degrading enzymes present in male antennae, suggesting that trifluoromethyl ketones are not sufficiently electrophilic to produce a stable intermediate adduct with a cysteine residue of the enzyme, a mechanism previously proposed for oxidase inhibition in insects. Overall and taking into account our previous reports and, particularly, the reduction in damage induced in maize fields by a trifluoromethyl ketone analogue of the pheromone of Sesamia nonagrioides (Sole, J.; Sans, A.; Riba, M.; Rosa, E.; Bosch, M. P.; Barrot, M.; Palencia, J.; Castella, J.; Guerrero, A. Reduction of damage by the Mediterranean corn borer, Sesamia nonagrioides , and the European corn borer, Ostrinia nubilalis , in maize fields by a trifluoromethyl ketone pheromone analog . Entomol. Exp. Appl. 2008, 126, 28-39), the antagonist might be a new candidate to consider in future strategies to control the codling moth.

Antagonism of pheromone response of Ostrinia nubilalis males and implications on behavior in the laboratory and in the field.

The antagonistic effect on the pheromone response and catabolism of male European corn borers, Ostrinia nubilalis, by several trifluoromethyl ketones is reported. (Z)-11-Tetradecenyl trifluoromethyl ketone (Z11-14:TFMK), the most closely related analogue of the main component of the pheromone, elicits a remarkable disruptive effect on close approach and source contact of males flying to a source baited with mixtures of the pheromone and the antagonist in 5:1 and 10:1 ratios. In this experiment, the male displayed an erratic flight track with frequent counter turns and intersections with the plume. In the field, the TFMK significantly lowered the number of males caught when mixed with the pheromone in a 10:1 ratio in comparison with the natural attractant. The compound was also a good inhibitor of the antennal esterase of the insect with a IC(50) value of 0.28 muM. The homologous (Z)-10-tridecenyl trifluoromethyl ketone, with one carbon less in the chain, also elicited an antagonistic effect in the wind tunnel, but in the field, the results were not conclusive. The effect induced was lower than the one displayed by Z11-14:TFMK including the activity as the esterase inhibitor (IC(50) value of 7.55 muM). The saturated tetradecyl trifluoromethyl ketone, tetradecyltrifluoropyruvamide, and (Z)-11-2-thiatetradecenyl trifluoromethyl ketone resulted completely inactive. The results obtained in conjunction to the previously shown low toxicity to mice by related trifluoromethyl ketones provide new important data for the putative utilization of these chemicals as new pest control agents.

Biorational approaches for insect control by enzymatic inhibition.

Conventional insecticides are highly toxic to many living organisms as well as to the environment; consequently, new biorational and more specific approaches to pest control have been developed. In this paper, we present an update of those approaches resulting from studies on inhibition of enzymes involved in key processes of insects life, particularly growth, molting and development of larvae and intraspecific communication of adults. The enzymes covered include pheromone degrading enzymes, pheromone biosynthetic enzymes, oxidoreductases, juvenile hormones, juvenile hormone epoxide hydrolases, proteases, molting hormones and phenoloxidases. Although these approaches refer to control of insect pests, many of them can be in principle also considered suitable for medicinal chemistry studies, since the mechanism of action of these inhibitors on related enzymes is quite similar, if not equal, in both fields.