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

Abstract

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.

Efficacy of broflanilide (VECTRON T500), a new meta-diamide insecticide, for indoor residual spraying against pyrethroid-resistant malaria vectors

“…Indeed, recent studies in which broflanilide was tested against a strain of An. gambiae Kisumu containing mutations in the GABA receptor conferring resistance to dieldrin (RDL), found a very low resistance ratio (1.73) compared to the susceptible Kisumu strain which would indicate the absence of cross-resistance to broflanilide and dieldrin 37 . Mutations in the GABA receptor which confer resistance to meta-diamides have however been detected in Drosophila 20 .…”

Efficacy of indoor residual spraying with broflanilide (TENEBENAL), a novel meta-diamide insecticide, against pyrethroid-resistant anopheline vectors in northern Tanzania: An experimental hut trial

“…Broflanilide N -[2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl]-2-fluoro-3-( N -methylbenzamido)benzamide] is a novel active ingredient developed by Mitsui Chemicals Agro Inc. (MCAG; Tokyo, Japan) [ 13 ] that has potential for use in vector control, including the control of mosquitoes which have become resistant to pyrethroids and potentially other classes of insecticide [ 14 ]. Broflanilide (tradename TENEBENAL TM ) is a meta-diamide insecticide that has a different mode of action compared to all other insecticides currently used in public health [ 15 ].…”

Modern groups of insecticides: diamides and meta-diamides

“…группам инсектицидов, которые в настоящее время используются для борьбы с переносчиками. Соединение показало высокую активность в лабораторных и полевых исследованиях и требует дальнейших исследований в целях борьбы с устойчивыми к пиретроидам комарами (Lees et al, 2020;Ngufor et al, 2021;Snetselaar et al, 2021). В Бенине показана высокая и продолжительная активность средства в форме 50 % смачивающегося порошка «VECTRON T500» против Anopheles gambiae s.l.…”