Isocycloseram (isocycloseram)

Isocycloseram (isocycloseram) represents a significant milestone in the development of modern insecticides, constituting a systemic compound of the isoxazoline class developed by Syngenta and commercially introduced in the Brazilian market in 2023.

The historical trajectory of the development of isoxazolines as an insecticide class dates back to the laboratories of Nissan Chemical Industries, where they were initially discovered (Cassayre, et all., 2021, doi.org/10.1016/B978-0-12-821035-2.00008-5).

Subsequently, multiple agrochemical companies directed efforts towards improving this class, and in the specific case of Syngenta, researchers reported a fortuitous discovery during investigations with 1,2-diamide compounds.

The Plinazolin trademark registration was initially applied for in Switzerland in May 2018, followed by submission in Brazil in July of the same year, culminating in commercial availability five years later.

Common name (ISO): Isocycloseram (isocycloseram)

Official chemical name: (5S,8R)-N-[(5-bromo-2-metoxipiridin-3-il)metil]-5-(clorodiflluorometil)-3,4,5,6,7,8-hexahidro-8-metilpirido[4,3-d][1,2]oxazina-2-carboxamida

Gross chemical formula: C₁₇H₁₉BrClF₂N₄O₃

Number CAS: 2061933-85-3

Chemical class: Isoxazolines (isoxazolines)

Synonyms: Atexzo ANT-F; Frondeo; poppet; Verdavis; Vulter (commercial product brands)

Patents: WO/2007/080131 (initial, 2007); WO/2009/080250 (2009); WO 2022128912 A1 (2022); US 20230000082 A1 (2023); AU 2022251931 A1 (2023) and others.

Mechanism of action

Isocycloseram operates through a highly specific biochemical mechanism, acting as an allosteric modulator of GABA (gamma-aminobutyric acid) receptors in the central nervous system of insects.

The uniqueness of this mechanism lies in the fact that the compound binds to GABA receptors at a site of action distinct from that used by other classes of insecticides, particularly fiproles (IRAC Group 2B) and cyclodienes (IRAC Group 2A). This characteristic has given isocycloseram classification in IRAC (Insecticide Resistance Action Committee) Group 30, called "Allosteric Modulators of GABA-Gated Chloride Channels".

The biochemical process triggered by the action of isocycloseram involves the inhibition of the influx of chloride ions through GABA-gated channels, resulting in a cascade of events that culminates in the hyperexcitation of the insect's nervous system.

Studies conducted with Drosophila melanogaster demonstrated that the symptoms induced by isocycloseram are comparable to those observed with dieldrin, characterized by muscle hypercontraction and immobility of the larvae, evidencing the interruption of normal nervous and muscular physiology.

The onset of characteristic symptoms occurs relatively quickly, with signs of hyperarousal being observed within a few hours of exposure.

Typical progression involves an initial phase of hyperexcitation followed by paralysis and eventual mortality, a process that is normally completed within 24 to 48 hours, depending on the target species and the concentration of the active ingredient applied.

Control spectrum

Isocycloseram demonstrates remarkable breadth in its control spectrum, presenting high efficacy against several orders of insects of agricultural importance.

Among the species controlled with greater efficiency, representatives of the order Lepidoptera stand out, including Spodoptera frugiperda, Helicoverpa armigera e Chrysodeixis includens.

In the order Hemiptera, the active ingredient demonstrates excellent performance against Bemisia tabaci (whitefly), several species of Aphis (aphids) and complexes of phytophagous bugs.

The effectiveness also extends to beetles, especially Diabrotica speciosa (little cow) and other soil pests, in addition to thrushes such as thrips spp. and diptera of agricultural importance.

Partial control is observed in specific situations, particularly with large lepidopterans in advanced stages of development, some species of mites where isocycloseram presents secondary activity, and in conditions of high population pressure where the pests are already established.

On the other hand, tolerance or resistance may manifest in species that have developed cross-resistance to other GABA modulators, insects carrying specific mutations in the GABA receptor (such as the G335M mutation documented in laboratory studies), and pests with enhanced metabolic detoxification mechanisms.

Technical guidelines for application

The technical recommendations for the application of isocycloseram are based on extensive efficacy and selectivity studies. The recommended dosage is in the range of 60 to 120 grams of active ingredient per hectare, and may be increased to 150 g ai/ha in situations of high pest pressure. The spray volume should be adjusted between 100 and 300 liters per hectare, depending on the crop and application equipment used.

The ideal time for application is characterized by a preventive approach or intervention at the beginning of the infestation. For lepidopterans, application is recommended preferably directed at eggs and first and second instar larvae, when susceptibility is maximum. Monitoring through specific traps and regular sampling is a fundamental practice to determine the appropriate time for intervention.

Weather conditions have a significant influence on the effectiveness of the product. The ideal temperature is between 15 and 30°C, with relative humidity between 50 and 80%. Wind speed should not exceed 10 km/h during application, and there must be no precipitation for 4 to 6 hours after application. Preferably, application should be made in the late afternoon or early morning to optimize absorption conditions and minimize losses due to volatilization or photolytic degradation.

Compatibility and mixing strategies

Isocycloseram is compatible with other agrochemicals and is therefore suitable for integration into management programs. The active ingredient is compatible with most systemic fungicides, selective post-emergence herbicides, foliar fertilizers and organosilicone adjuvants. This feature facilitates the implementation of integrated application strategies, optimizing field operations and reducing operating costs.

The most commonly used mixtures include combinations with triazole fungicides for simultaneous control of pests and diseases, combinations with contact insecticides for broadening the spectrum and obtaining a shock effect, mixtures with growth regulators for integrated pest management, and combinations with specific acaricides for controlling the pest-mite complex. These combinations should be based on studies of physical-chemical compatibility and biological efficacy.

However, certain mixtures should be avoided due to the potential for incompatibility or reduced efficacy. Highly alkaline products with a pH greater than 8,5, organophosphate insecticides in high concentrations, products containing copper in incompatible formulations and mineral oil in high concentrations without prior compatibility testing constitute combinations that may compromise the performance of isocycloseram.

Resistance and sustainability

The issue of resistance represents a critical aspect for the sustainability of isocycloseram as a control tool. To date, there are no consolidated reports of field resistance to isocycloseram in Brazil.

However, laboratory studies have identified the potential for development of resistance through mutations in the GABA receptor, particularly the G335M mutation. The possibility of cross-resistance with other GABA modulators demands special attention in the development of management strategies.

Recommendations for rotation of mechanisms of action include alternating insecticides from IRAC Groups 5 (spinosyns), 11A (Bacillus thuringiensis) and 22A (oxadiazines), avoiding consecutive applications of the same chemical group. Implementing biological windows between applications and integrating biological control methods and cultural practices are fundamental elements of the resistance management strategy.

Practical strategies for resistance management involve rigorous rotation of action mechanisms for each generation of the pest, maintenance of structured refuges representing at least 10% of the cultivated area, constant monitoring of population susceptibility through bioassays, use of recommended doses to avoid underdosing, integration with biological and cultural methods, and application of the principles of Integrated Pest Management (IPM).

Agronomic efficiency

The agronomic efficacy of isocycloseram is influenced by several environmental and operational factors.

Precipitation in the first 4 to 6 hours after application significantly reduces effectiveness due to washing the product off before it is completely absorbed.

Water stress conditions can compromise the absorption and translocation of the active ingredient, while extreme temperatures, below 10°C or above 35°C, negatively affect biological activity. Relative humidity below 40% can impair foliar penetration and consequent product efficacy.

The advantages of isocycloseram include its novel mechanism of action classified in IRAC Group 30, broad spectrum of control, systemic action with translocation capacity, low toxicity to mammals, compatibility with IPM programs, prolonged residual and selectivity for natural enemies when used at recommended doses. These characteristics position the product as a valuable tool for sustainable pest management.

Positioning in specific agricultural systems

In the culture of soybean, isocycloseram is ideally positioned to control the caterpillar complex, including Anticarsia gemmatalis, Chrysodeixis includens e Helicoverpa armigera, in addition to whiteflies. Their use should be strategically planned in rotation with Bt and spinosyn technologies to maximize management sustainability.

For the culture of corn, the product represents an excellent option for controlling Spodoptera frugiperda resistant to other mechanisms of action and should be integrated into rotational programs with diamides and organophosphates. Efficacy against this specific pest is particularly relevant considering the growing resistance challenges observed in Brazil.

Na cotton farming, isocycloseram is a strategic tool in the management of the complex helicoverpa e spodoptera, especially in areas with a history of pyrethroid resistance. Its integration into management programs should consider the high pest pressure characteristic of this crop.

To sugar cane, the application aimed at Diatraea saccharalis and other specific pests must be planned in integration with already established biological control programs, respecting selectivity for parasitoids and predators.

Na horticulture, the use in high value-added crops is justified by the focus on controlling resistant pests and the need for intensive rotation programs, contributing to the sustainability of production systems.

Isocycloseram belongs to the group of per- and polyfluoroalkyl substances (PFAS). These substances are defined by the Organisation for Economic Co-operation and Development (OECD) as any chemical compound containing at least one fully fluorinated methyl (CF3-) or methylene (CF2-) carbon atom.