Discovery of broflanilide, a novel insecticide

Katsuta, Hiroyuki; Nomura, Michikazu; Wakita, Takeo; Daido, Hidenori; Kobayashi, Yumi; Kawahara, Atsuko; Banba, Shinichi

doi:10.1584/jpestics.d18-088

Cited by 67 publications

(64 citation statements)

References 9 publications

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“…Tenebenal™ (broflanilide), was one of the meta-diamides [ N -[2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-( N -methylbenzamido)benzamide] discovered by Mitsui Chemicals Agro Inc. during drug discovery research, a compound with a structure unique among agricultural insecticides and with high activity against several arthropod pest species [ 4 ]. Broflanilide was assigned to a new IRAC MoA class 30 (Meta-diamides and Isoxazolines) by the Insecticide Resistance Action Committee (IRAC), due to its novel mode of action [ 5 ], as an ionotropic γ-aminobutyric acid (GABA)-gated chloride channel allosteric modulator.…”

Section: Introductionmentioning

confidence: 99%

“…Broflanilide was assigned to a new IRAC MoA class 30 (Meta-diamides and Isoxazolines) by the Insecticide Resistance Action Committee (IRAC), due to its novel mode of action [ 5 ], as an ionotropic γ-aminobutyric acid (GABA)-gated chloride channel allosteric modulator. Exposure of Lepidoptera to meta-diamides causes symptoms including vomiting and vigorous excitation [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…The compound is scheduled to be released onto the market in 2020 for agricultural use [ 4 ]. Mitsui Chemicals Agro Inc. initiated a collaboration with the Innovative Vector Control Consortium (IVCC) [ 6 ] which evaluated the compound for efficacy against mosquito species at the Liverpool Insect Testing Establishment (LITE), Liverpool School of Tropical Medicine (LSTM).…”

Section: Introductionmentioning

confidence: 99%

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Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health

Lees

Ambrose

Williams

et al. 2020

Malar J

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Background There is an urgent need for insecticides with novel modes of action against mosquito vectors. Broflanilide is a meta-diamide, discovered and named Tenebenal™ by Mitsui Chemicals Agro, Inc., which has been identified as a candidate insecticide for use in public health products. Methods To evaluate its potential for use in public health, Tenebenal™ was screened using an array of methodologies against Anopheles and Aedes strains. Initially it was assessed for intrinsic efficacy by topical application. Tarsal contact bioassays were then conducted to further investigate its efficacy, as well as its potency and speed of action. The potential of the compound for use in indoor residual spray (IRS) applications was investigated by testing the residual efficacy of a prototype IRS formulation on a range of typical house building substrates, and its potential for use in long-lasting insecticidal nets (LLIN) was tested using dipped net samples. Finally, bioassays using well-characterized insecticide-resistant mosquito strains and an in silico screen for mutations in the insecticide’s target site were performed to assess the risk of cross-resistance to Tenebenal™. Results Tenebenal™ was effective as a tarsal contact insecticide against both Aedes and Anopheles mosquitoes, with no apparent cross-resistance caused by mechanisms that have evolved to insecticides currently used in vector control. Topical application showed potent intrinsic activity against a Kisumu reference strain and an insecticide-resistant strain of Anopheles gambiae. Applied to filter paper in a WHO tube bioassay, Tenebenal™ was effective in killing 100% of susceptible and resistant strains of An. gambiae and Aedes aegypti at a concentration of 0.01%. The discriminating concentration of 11.91 µg/bottle shows it to be very potent relative to chemistries previously identified as having potential for vector control. Mortality occurs within 24 h of exposure, 80% of this mortality occurring within the first 10 h, a speed of kill somewhat slower than seen with pyrethroids due to the mode of action. The potential of Tenebenal™ for development in LLIN and IRS products was demonstrated. At least 12 months residual efficacy of a prototype IRS formulation applied at concentrations up to 200 mg of AI/sq m was demonstrated on a range of representative wall substrates, and up to 18 months on more inert substrates. A dipped net with an application rate of around 2 g/sq m Tenebenal™ killed 100% of exposed mosquitoes within a 3-min exposure in a WHO cone test. Conclusions Tenebenal™ is a potent insecticide against adult Aedes and Anopheles mosquitoes, including strains resistant to classes of insecticide currently used in vector control. The compound has shown great potential in laboratory assessment and warrants further investigation into development for the control of pyrethroid-resistant mosquitoes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health

Lees

Ambrose

Williams

et al. 2020

Malar J

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“…63,64) Broflanilide (Vedira ™ , Tenebenal ™ , Mitsui Chemicals Agro), currently being jointly developed with BASF, has a unique chemical structure characterized as a meta-diamide and exhibits high activity against various pests, including lepidopteran, coleopteran, and thysanopteran pests. 65,66) Broflanilide received the first registration worldwide in Australia in January 2020. Broflanilide is metabolized to desmethyl-broflanilide, and it acts as a noncompetitive resistant-to-dieldrin (RDL) γ-aminobutyric acid (GABA) receptor antagonist.…”

Section: Trends In Novel Insecticides Other Than Nicotinic and Diamidementioning

confidence: 99%

Development of novel pesticides in the 21st century

2020

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General trends and strategies for novel pesticides are summarized. Global pesticide sales and pesticide discovery research are also briefly reviewed. At least 105 chemical pesticides have been launched during the past decade or are under development: 43 fungicides, 34 insecticides/acaricides, 6 nematicides, 21 herbicides, and 1 herbicide safener. Most of them are safe to humans and environmentally friendly. The most developed fungicides are SDHI (succinate dehydrogenase inhibitors), DMI (demethylation inhibitors), QoI (quinone outside inhibitors), and QiI (quinone inside inhibitors). Due to the development of resistance to fungicides with existing modes of action, many fungicides possessing various novel modes of action have been launched or are under development. The trend of insecticide development is changing from organophosphorus, carbamate, and synthetic pyrethroids to nicotinic and diamide insecticides. During the past decade, compounds possessing a variety of novel modes of action have also been launched or are under development. Flupyradifurone and flupyrimin, exhibiting extremely low honeybee toxicity, have been developed and subjected to practical use. Herbicides possessing varied modes of action, such as acetolactate synthase, p-hydroxyphenylpyruvate dioxygenase, protoporphyrinogen oxidase, and very-long-chain fatty acid elongase inhibition, have been developed, but no herbicides possessing a novel mode action have commercialized in nearly 30 years. It is of interest that cyclopyrimorate, which was recently launched, and tetflupyrolimet, which is under development, have novel modes action: homogentisate solanesyltransferase (HST) and dihydroorotate dehydrogenase (DHODH) inhibition, respectively. The development of useful acaricides and nematicides is also progressing. Some natural product origin pesticides are getting attention.

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“…Conversely, for activity against cotton bollworm (Helicoverpa armigera), a combination of bromine, trifluoromethyl group and the strong lipophilic heptafluoro-iso-propyl substituent has to be present. 25 Broflanilide has broad-spectrum activity (crop and non-crop pests) and can be used in different crops to control lepidoptera, coleoptera, termites, ants, cockroaches, and flies. The pro-insecticide broflanilide is probably metabolized by CYP 450mediated bioactivation of its insecticidally active des-methylbroflanilide (cleavage of the N-methyl group).…”

Section: Meta-diamidesmentioning

confidence: 99%

Status and outlook for acaricide and insecticide discovery

Jeschke

2020

Pest Management Science

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To guarantee sustainability and progress, the agrochemical industry is faced with several major challenges. Currently, loss of active ingredients due to consumer perception, changing grower needs and ever-changing regulatory requirements is far higher than the number being introduced into the market. Therefore, there is a need to develop new products that can provide improved efficacy, selectivity and favorable environmental profiles. Strategies to achieve these goals are the search for acaricides and insecticides with new modes of action, or the discovery of novel molecules with activity on the most attractive target sites having resistance breaking properties against pest species. In this context, the introduction of halogen atoms or asymmetric centers into an active ingredient remains an important tool to modulate their properties, but so too is the pro-pesticide concept. This review gives an overview of agrochemicals launched over the past 8 years, reflects new insights into known mechanisms of action, and describes the status and outlook for acaricide and insecticide discovery. Supporting information may be found in the online version of this article.

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Discovery of broflanilide, a novel insecticide

Cited by 67 publications

References 9 publications

Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health

Tenebenal: a meta-diamide with potential for use as a novel mode of action insecticide for public health

Development of novel pesticides in the 21st century

Status and outlook for acaricide and insecticide discovery

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