Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cis-Neonicotinoid Compound with a Unique Oxabridged Substructure

Abstract

Insecticide synergists are key components to increase the control efficacy and reduce active ingredient use. Here, we describe a novel insecticide synergist with activity specific for insecticidal neonicotinoids. The synergist IPPA08, a cis configuration neonicotinoid compound with a unique oxabridged substructure, could increase the toxicity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4A subgroup against a range of insect species, although IPPA08 itself was almost inactive to insects at synergistic concentrations. Unfortunately, similar effects were observed on the honey bee (Apis mellifera) and the brown planthopper (Nilaparvata lugens), resistant to imidacloprid. IPPA08 did not show any effects on toxicity of insecticides with different targets, which made us define it as a neonicotinoid-specific synergist. Unlike most insecticide synergists, by inhibition of activities of detoxification enzymes, IPPA08 showed no effects on enzyme activities. The results revealed that IPPA08 worked as a synergist through a distinct way. Although the modulating insect nicotinic acetylcholine receptors (nAChRs, targets of neonicotinoid insecticides) were supposed as a possible mode of action for IPPA08 as a neonicotinoid-specific synergist, direct evidence is needed in further studies. In insect pest control, IPPA08 acts as a target synergist to increase neonicotinoid toxicity and reduce the amount of neonicotinoid used. Combinations of IPPA08 and insecticidal neonicotinoids may be developed into new insecticide formulations. In summary, combining an active ingredient with a "custom" synergist appears to be a very promising approach for the development of effective new insecticide products.

The Mechanism by Which Dodecyl Dimethyl Benzyl Ammonium Chloride Increased the Toxicity of Chlorpyrifos to Spodoptera exigua

“…Many synergists exhibit synergistic effects on the toxicity of insecticides, and the synergistic mechanism of most synergists is through inhibiting the detoxification eznymes activities, such as PBO inhibiting P450 monooxygenases activities, TPP inhibiting ESTs activities, and DEM inhibiting GSTs activities (Bao et al, 2016). To find out whether DDBAC showed inhibition effects on the activities of detoxification enzymes, DDBAC was applied to insects and then the changes in enzyme activities were determined.…”

“…Reducing pesticide application, increasing unit activity and selectivity, and reducing pesticide resistance development rate are important ways to deal with this dilemma. And the application of synergists is an effective strategy to increase pesticides toxicity and reduce pesticides usage amount (Bao et al, 2016). Here, we found that DDBAC, a cationic adjuvant, showed significant enhancement effect on chlorpyrifos, although DDBAC itself was inactive against insect pests at these synergistic concentrations.…”

“…For example, piperonyl butoxide (PBO) has been widely used as a synergist for insecticide formulation. It plays an important role in the control of insect pests (Jewess, 2000; Bao et al, 2016). Besides, triphenyl phosphate (TPP) and diethyl maleate (DEM) are also important synergists through inhibiting the detoxification enzymes activities (Wang et al, 2013, 2014).…”

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 1: new molecules, metabolism, fate, and transport

“…This is the case for IPPA08, an eight-membered homolog of the cis-neonicotinoid cycloxaprid that can be used as neonicotinoid-specific synergist (Bao et al 2016). However, IPPA08 increases the toxicity of several neonicotinoid insecticides (i.e., acetamiprid, thiacloprid, clothianidin, and imidacloprid) to nontarget species as well, such as honeybees and the brown planthopper (Nilaparvata lugens) (Bao et al 2016).…”

“…This is the case for IPPA08, an eight-membered homolog of the cis-neonicotinoid cycloxaprid that can be used as neonicotinoid-specific synergist (Bao et al 2016). However, IPPA08 increases the toxicity of several neonicotinoid insecticides (i.e., acetamiprid, thiacloprid, clothianidin, and imidacloprid) to nontarget species as well, such as honeybees and the brown planthopper (Nilaparvata lugens) (Bao et al 2016). Also, the root fertilizer BRoot Feed^(i.e., 9% N, 7% Ca, 1.5% Mg, and 0.1% B) subirrigated in the growing medium has been able to enhance imidacloprid efficacy against the whitefly on tomato (Sun and Liu 2016).…”