Discovery of novel (N-aryl-4-methylpiperidinyl)pyrazoles: a new class of potent lepidopteran insecticides.

BACKGROUND: Insects of the order Lepidoptera are among the most destructive global pests, causing billions of dollars in damage annually. A new class of N-arylpyrazole-4-methylpiperidines with potent activity on lepidopteran species has been discovered. RESULTS: In a high-throughput insecticide screen compound 1 was identified to possess modest activity on the lepidopteran insect Plutella xylostella. Optimization of 1 to compound 42 resulted in a compound with excellent activity on Spodoptera exigua, Spodoptera frugiperda, and Helicoverpa zea with median lethal concentrations values of 2.8, 1.4, and 12.5 ppm respectively. Although the mode of action remains unknown, these compounds do not appear to work by many of the known biochemical mechanisms of insect control. CONCLUSION: N-Arylpyrazole-4-methylpiperidines represent a new class of insecticides with excellent activity on a broad spectrum of lepidopteran pests. Studies to date indicate the potential for a novel mode of action; however, the target site is unknown at present. © 2023 Society of Chemical Industry.

Pyrrole-2 carboxamides - A novel class of insect ryanodine receptor activators.

The ryanodine receptor (RyR) is an intracellular calcium channel critical to the regulation of insect muscle contraction and the target site of diamide insecticides such as chlorantraniliprole, cyantraniliprole and flubendiamide. To-date, diamides are the only known class of synthetic molecules with high potency against insect RyRs. Target-based screening of an informer library led to discovery of a novel class of RyR activators, pyrrole-2-carboxamides. Efforts to optimize receptor activity resulted in analogs with potency comparable to that of commercial diamides when tested against RyR of the fruit fly, Drosophila melanogaster. Surprisingly, testing of pyrrole-2-carboxamides in whole-insect screens showed poor insecticidal activity, which is partially attributed to differential selectivity among insect receptors and rapid detoxification. Among various lepidopteran species field resistance to diamide insecticides has been well documented and in many cases has been attributed to a single point mutation, G4946E, of the RyR gene. As with diamide insecticides, the G4946E mutation confers greatly reduced sensitivity to pyrrole-2-carboxamides. This, coupled with findings from radioligand binding studies, indicates a shared binding domain between anthranilic diamides and pyrrole-2-carboxamides.

Mesoionic pyrido[1,2-a]pyrimidinones: Discovery of triflumezopyrim as a potent hopper insecticide1.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program which led to the discovery of triflumezopyrim as a highly potent insecticide controlling various hopper species. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.

Mesoionic insecticides: a novel class of insecticides that modulate nicotinic acetylcholine receptors.

BACKGROUND: As the world population grows towards 9 billion by 2050, it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields owing to pests. The development of new insecticides will help to sustain this protection and overcome insecticide resistance. RESULTS: A novel class of mesoionic compounds has been discovered, with exceptional insecticidal activity on a range of Hemiptera and Lepidoptera. These compounds bind to the orthosteric site of the nicotinic acetylcholine receptor and result in a highly potent inhibitory action at the receptor with minimal agonism. The synthesis, biological activity, optimization and mode of action will be discussed. CONCLUSION: Triflumezopyrim insect control will provide a powerful tool for control of hopper species in rice throughout Asia. Dicloromezotiaz can provide a useful control tool for lepidopteran pests, with an underexploited mode of action among these pests. © 2016 Society of Chemical Industry.

Movement of cyantraniliprole in plants after foliar applications and its impact on the control of sucking and chewing insects.

BACKGROUND: Given the physical properties of insecticides, there is often some movement of these compounds within crop plants following foliar application. In this context, movement of two formulations of cyantraniliprole, an anthranilic diamide, was characterized for translocation to new growth, distribution within a leaf and penetration through the leaf cuticle. RESULTS: Upward movement of cyantraniliprole to new plant growth via the xylem was confirmed using (14) C-radiolabeled cyantraniliprole and from Helicoverpa zea mortality on tomato leaves that had not been directly treated. Within a leaf there was significant acropetal movement (base to apex) of cyantraniliprole, but no significant basipetal movement (apex to base). Translaminar movement, the ability of a compound to penetrate the leaf cuticle, was demonstrated in a variety of plants, both with and without the use of adjuvants, by treating only the adaxial surface of the leaf and measuring control of diamondback moth (Plutella xylostella), green peach aphid (Myzus persicae) and sweetpotato whitefly (Bemisia tabaci) exposed in clip cages to the untreated abaxial surface. CONCLUSION: The plant mobility and plant protection of cyantraniliprole is discussed with implications for use in insect resistance management and integrated pest management programs.

Insecticidal quinoline and isoquinoline isoxazolines.

A series of quinoline and isoquinoline isoxazolines have been designed as pesticides for crop protection. Herein we reported the chemical synthesis, biological activity and structure-activity relationships. The isoquinoline derivative, such as 3i, is discovered as potent new class of isoxazoline insecticide which is competitive with commercial insecticide Indoxacarb.

Discovery, synthesis, and evaluation of N-substituted amino-2(5H)-oxazolones as novel insecticides activating nicotinic acetylcholine receptors.

N-Substituted amino-2(5H)-oxazolones A are a novel class of insecticides acting as nicotinic acetylcholine receptor (nAChR) agonists and show potent activity against hemipteran insect species. Here we report the discovery and preparation of this class of chemistry. Our efforts in SAR elucidation, biological activity evaluation, as well as mode-of-action studies are also presented.

Discovery of cyantraniliprole, a potent and selective anthranilic diamide ryanodine receptor activator with cross-spectrum insecticidal activity.

Anthranilic diamides are an exceptionally active class of insect control chemistry that selectively activates insect ryanodine receptors causing mortality from uncontrolled release of calcium ion stores in muscle cells. Work in this area led to the successful commercialization of chlorantraniliprole for control of Lepidoptera and other insect pests at very low application rates. In search of lower logP analogs with improved plant systemic properties, exploration of cyano-substituted anthranilic diamides culminated in the discovery of a second product candidate, cyantraniliprole, having excellent activity against a wide range of pests from multiple insect orders. Here we report on the chemistry, biology and structure-activity trends for a series of cyanoanthranilic diamides from which cyantraniliprole was selected for commercial development.

4-Azolylphenyl isoxazoline insecticides acting at the GABA gated chloride channel.

Isoxazoline insecticides have been shown to be potent blockers of insect GABA receptors with excellent activity on a broad pest range, including Lepidoptera and Hemiptera. Herein we report on the synthesis, biological activity and mode-of-action for a class of 4-heterocyclic aryl isoxazoline insecticides.

Seasonal abundance, life history, and parasitism of Caloptilia porphyretica (Lepidoptera: Gracillariidae), a leafminer of highbush blueberry.

The leafminer Caloptilia porphyretica Braun (Lepidoptera: Gracillariidae), has become a frequent pest in commercial highbush blueberries, Vaccinium corymbosum L., in New Jersey, but little is known about its seasonal abundance, life history, and parasitism rates. Monitoring programs were conducted from 2003 to 2006 on seven blueberry farms to determine the relative abundance of this leafminer by using pheromone-baited traps and by sampling vegetative and flower/fruit clusters and new shoot growth. We found at least three distinct generations per year, with populations reaching their highest peak in the second generation. Laboratory studies characterized the life history of C. porphyretica and its parasitoid Pholetesor sp. prob. salalicus (Mason). The developmental period of C. porphyretica, from egg to adult, took 927, 838, and 912 degree-days (DD) at 20, 25, and 30 degrees C, respectively, by using a developmental threshold of 4.8 degrees C. This was equivalent to an average of 892 DD to complete development to adult, which compared with 870 and 880 DD between the first and second, and second and third generations, respectively, by using pheromone trap data averaged from 2004 to 2006. Although C. porphyretica populations varied greatly, the number of larvae in cluster and new shoot samples was highly correlated with the number of adults in traps. Field parasitism rate was -29%, with the braconid Pholetesor sp. the most abundant parasitoid. Ten of the 13 parasitoid species collected belonged to the family Eulophidae. When different ages of leafminers were exposed to Pholetesor sp., we found that the parasitoid attacks 9-15-d-old instars that reside in the mines of leaves.

Optimization of pheromone deployment for effective mating disruption of oriental beetle (Coleoptera: Scarabaeidae) in commercial blueberries.

Cost is a potential limiting factor in the adoption of mating disruption to control oriental beetle, Anomala orientalis (Waterhouse) (Coleoptera: Scarabaeidae). A 3-yr study was conducted in 1-ha blueberry, Vaccinium corymbosum L., plots to test the possibility of lowering cost by reducing the number of point-source dispensers and pheromone [(Z)-7-tetradecen-2-one] concentrations, while maintaining mating disruption. Trap shutdown, as measured by the disruption index (DI), caged females, and sentinel potted-plants with tethered females were used to assess the success of mating disruption. Disrupted plots had DI values of > or = 93% in all years, and a lower percentage of mated females, compared with control plots. However, DI values were > or = 95% at > or = 50 dispensers per ha. When 25 dispensers containing 0.05 g of active ingredient (AI) were used per hectare, the numbers of males in female cages and larvae in sentinel pots were similar to controls. Thus, dispenser density was critical for successful mating disruption of oriental beetles. Male oriental beetles approach the dispensers at all times of the day according to field observations, indicative of competitive attraction as a potential mechanism for mating disruption. However, at peak activity, greater male attraction was observed to dispensers containing 0.1 g of pheromone than 0.05 or 0.025 g, demonstrating the importance of pheromone rate. Although dispensers continued to emit pheromone for at least 7 wk in the field, emission rates dropped to levels close to 0 after 3 wk. We conclude that deployment of > or = 50 dispensers/ha at > or = 0.1 g (AI) per dispenser is the most effective rate for mating disruption of oriental beetle in blueberries.

New and selective ryanodine receptor activators for insect control.

Diamide insecticides have emerged as one of the most promising new classes of insecticide chemistry owing to their excellent insecticidal efficacy and high margins of mammalian safety. Chlorantraniliprole and flubendiamide, the first two insecticides from this class, demonstrate exceptional activity across a broad range of pests in the order Lepidoptera. This chemistry has been confirmed to control insects via activation of ryanodine receptors which leads to uncontrolled calcium release in muscle. The high levels of mammalian safety are attributed to a strong selectivity for insect over mammalian receptors.

A randomized controlled trial comparing treatment regimens for acute pain for topical oleoresin capsaicin (pepper spray) exposure in adult volunteers.

OBJECTIVE: Several topical therapies have been proposed to treat acute pain from exposure to oleoresin capsaicin (OC). The purpose of this study was to determine the most beneficial topical treatment for relieving contact dermatitis pain caused by OC exposure. METHODS: We performed a single-blind, randomized human experiment evaluating the effectiveness of five different regimens for the treatment of topical facial OC exposure. Forty-nine volunteer, adult law enforcement trainees were exposed to OC during a routine training exercise and were randomized to one of five treatment groups (aluminum hydroxide-magnesium hydroxide [Maalox], 2% lidocaine gel, baby shampoo, milk, or water). After initial self-decontamination with water, subjects rated their pain using a 10-cm visual analog scale (VAS) and then every 10 minutes, for a total of 60 minutes. Subjects were blinded to previous VAS recordings. A two-factor analysis of variance (ANOVA) (treatment, time) with repeated measures on one factor (time) was performed using a 1.3-cm difference as clinically significant. RESULTS: Forty-four men and five women, with an average age of 24 years, participated in the study. There was a significant difference in pain with respect to time (p < 0.001), but no significant interaction between time and treatment (p > 0.05). There was no significant difference in pain between treatment groups (p > 0.05). CONCLUSION: In this study, there was no significant difference in pain relief provided by five different treatment regimens. Time after exposure appeared to be the best predictor for decrease in pain.

Synthesis of insecticidal fluorinated anthranilic diamides.

A series of highly active fluorinated anthranilic diamide insecticides have been prepared and their biological activity assessed on two aphid species in the search for systemically active compounds that control Hemiptera. In addition, we have demonstrated a new synthesis of N-aryl 3-fluoropyrazoles.

Effectiveness of protein baits on melon fly and oriental fruit fly (Diptera: Tephritidae): attraction and feeding.

Attraction and feeding responses of oriental fruit fly, Bactrocera dorsalis (Hendel), and melon fly, Bactrocera cucurbitae (Coquillett), were determined for different protein baits. In separate choice attraction assays for each species, significantly more flies arrived at stations with bait than water, but no differences existed among baits of GF-120 Fruit Fly Bait, GF-120 NF Naturalyte Fruit Fly Bait, Provesta 621 autolyzed yeast extract, and Mazoferm E802. In comparison with B. dorsalis, B. cucurbitae had 2.8 times more responders and a 4.8 times better discrimination between baits and water. In a second attraction assay with only B. dorsalis, volume of bait was negatively correlated to numbers of flies alighting on the bait. Feeding assays for both species demonstrated that time spent feeding and duration on a leaf were both significantly affected by bait type. B. dorsalis fed the longest on Provesta 621, with significantly less feeding on the other baits, and with all baits resulting in more feeding than water. The longest feeding times for B. cucurbitae resulted with Mazoferm E802 and Provesta 621, and all baits except GF-120 NF resulted in eliciting a significantly longer feeding duration than water. In separate toxicology assays for each species, significantly higher mortality resulted from bait formulations containing spinosad compared with blank baits, but no differences existed between GF-120 and GF-120 NF formulations. The differences are discussed between the two Bactrocera species primarily in regard to bait preference, extent of response, and previous work on laboratory flies.

Comparative effectiveness of different insecticides for organic management of blueberry maggot (Diptera: Tephritidae).

Laboratory and field assays using insecticides for organic pest management were conducted on the blueberry maggot, Rhagoletis mendax Curran. Topical exposure of flies to spinosad (Entrust), pyrethrum (PyGanic 1.4 EC), azadirachtin (Aza-Direct), and phosmet (Imidan 70-W) resulted in significantly higher mortality compared with the water control after 2 and 24 h. After 24 h, there were no significant differences in fly mortality among treatments of Entrust, PyGanic, or Imidan, whereas fly mortality to Aza-Direct was significantly lower. Another laboratory assay evaluated mortality of flies after residual exposure to these insecticides on leaves, after 24 and 48 h. In this assay, there were no significant differences in fly mortality after 48 h among treatments of PyGanic, Aza-Direct, and the water control, whereas significantly higher fly mortality resulted from exposure to Entrust and Imidan. A repellency assay found no measurable effects of Aza-Direct. Large-scale field trials found no treatment effect for number of adults of the blueberry maggot captured in sticky traps; however, there were significantly lower levels of fruit-infesting larvae in treated plots compared with the untreated control. Spinosad bait (GF-120 NF Naturalyte Fruit Fly Bait), Entrust, and PyGanic were not different from imidacloprid (Provado 1.6 F). However, there was a significantly higher infestation in the plot treated with azadirachtin (Agroneem) compared with Provado. Overall, the insecticides evaluated in these trials showed good ability to control blueberry maggot, suggesting that they can be incorporated in a blueberry maggot management program under organic standards.

Rattlesnake envenomation to the face of an infant.

BACKGROUND: Mortality from rattlesnake envenomation in the United States is rare. Despite approximately 8000 crotaline (pit vipers) bites annually, it is estimated that only 10 to 15 deaths occur. Besides direct intravascular envenomation and anaphylaxis, bites to the head and neck may account for some of these rare fatalities. We report a pediatric case of severe facial envenomation requiring emergent intubation and antivenom administration. CASE REPORT: A 14-month-old female toddler was envenomated by a Southern Pacific rattlesnake (Crotalus viridis helleri) above the right upper lip while playing in her backyard. Rapid swelling and ecchymosis developed, and the patient was airlifted to a pediatric tertiary care hospital. Within 3 hours, stridorous respirations complicated by significant facial and oropharyngeal edema necessitated emergent orotracheal intubation. A total of 16 vials of FabAV [Crotalidae Polyvalent Immune Fab (ovine) antivenom] were administered over the next 24 hours. The child gradually improved and was successfully extubated 5 days later. A 3-month follow-up demonstrated no significant cosmetic facial abnormalities. CONCLUSION: Crotaline bites to the head and neck have the potential for significant swelling and airway compromise. Facial bites, anaphylaxis, and rare intravascular envenomation may account for many of the fatalities from rattlesnake envenomation. Early intubation may be required to maintain airway patency.

Recapture of sterile Mediterranean fruit flies (Diptera: Tephritidae) in California's Preventative Release Program.

In southern California, the sterile insect technique has been used since 1994 to prevent establishment of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann). This method involves the continual mass release of sterile flies, which suppress or eliminate any introduced wild fly populations. In addition, Jackson traps baited with trimedlure are deployed throughout the preventative release region for the dual purpose of detecting wild flies and monitoring released sterile flies. Sterile fly recapture data for a 3-yr period was compared with climate and to host plant (in which traps were placed). Precipitation was negatively correlated; and temperature and relative humidity were positively correlated with fly recapture levels. The highest numbers of flies were recaptured during trapping periods associated with intermediate relative humidity and temperature, and low precipitation. Flies were recaptured throughout the entire year, in traps that had been frequently relocated to host plants with fruit. This finding suggests that these flies were capable of locating acceptable fruit in a variety of abiotic conditions. However, these data do not necessarily suggest that measurements unimportant in explaining sterile fly recapture are not of value in determining other outcomes important to the goals of sterile release programs, such as reducing the likelihood of establishment of an introduced wild Mediterranean fruit fly population. Future research might build on these results in developing more precise models useful in predicting recapture of sterile flies.

Feeding activity and attraction of blueberry maggot (Diptera: Tephritidae) to protein baits, ammonium acetate, and sucrose.

Attraction and feeding assays were conducted on blueberry maggot, Rhagoletis mendax Curran, to three protein baits, ammonium acetate, and sucrose. Flies fed significantly longer on concentrations of 25 and 50% SolBait than they did on any of the concentrations tested for Nu-Lure, AY50% (Mauri Yeast Australia), or a water control. The number of flies arriving at SolBait in an attraction assay was significantly higher than for Nu-Lure and a water control but was not different from AY50%. Flies fed less on aqueous solutions of 1 and 4% ammonium acetate, a known fruit fly attractant, than they did on either 0.25% ammonium acetate or water. Aqueous concentrations of 8, 16, and 32% sucrose elicited greater feeding responses from flies than either 4% sucrose or water. These findings suggest that SolBait is a superior protein bait based on attraction and feeding assays. Development of alternative baits should contain at least 8% sucrose, as a significant feeding stimulant, and some amount of ammonium acetate as an attractant. Future work should determine whether the feeding deterrence of ammonium acetate could be reduced or even eliminated in the presence of sucrose.

Phenology and infestation patterns of plum curculio (Coleoptera: Curculionidae) on four highbush blueberry cultivars.

The plum curculio, Conotrachelus nenuphar (Herbst), is a well known pest in apple and peach orchards, but it also is capable of having an economic impact in highbush blueberries. Host phenology and plum curculio oviposition patterns were determined on four highbush blueberry cultivars differing in fruit maturation period. Numbers of oviposition scars were higher on early- ('Weymouth') and mid-season ('Duke' and 'Bluecrop') blueberries than on late-season 'Elliott' in 2001, 2002, and 2003. In 2002, eggs were first present on the three earliest cultivars 21 d before those on 'Elliott', whereas eggs were found on 'Elliott' >40 d after the last sample with eggs for the other three cultivars. The pattern of host phenology and infestation levels suggested that plum curculio oviposition synchronizes well with the availability of suitable fruit for oviposition on early and mid-season cultivars compared with a late-season cultivar of highbush blueberries. The implications of a transition to use of reduced-risk insecticides are discussed in relation to plum curculio management.