Respiratory Inhibition of Acaricide AKD-2023 and Its Deacetyl Metabolite

Abstract

To define acaricidal mechanism of a new acaricidal AKD-2023 (2-acetoxy-3-n-dodecyl-l, 4naphthoquinone) and its metabolite, DHN (2-hydroxy-3-n-dodecyl-l, 4-naphthoquinone), the effects of these compounds on the respiration of flight-muscle mitochondria isolated from house flies were investigated. The inhibitory potency of AKD-2023 for succinate and pyruvate oxidation activity was much less than that of DHN. This result suggested that the hydrolyzed metabolite, DHN is virtually biologically active and inhibits the respiration of mitochondria. It was also proved that the inhibition occurs at the complex III in mitochondrial electron transfer chain. On the basis of reduction kinetics of cytochromes b and c1, the binding site was shown to be ubiquinol oxidation site (Q0 center) of complex III, being different from that of other acaricides developed recently.

Mode of action of novel acaricide pyflubumide: Effects on the mitochondrial respiratory chain

“…Many acaricides have been developed with different modes of action, 2) including mitochondrial complex I (NADH-quinone oxidoreductase) inhibition, 3) mitochondrial complex III (quinolcytochrome c oxidoreductase) inhibition, 4) ATP synthesis inhibition, 5) oxidative phosphorylation uncoupling, 6) octopamine receptor agonism, 7) lipid biosynthesis inhibition, 8) chitin biosynthesis inhibition, 9) and so on. The most recently developed class of acaricides are mitochondrial complex II (succinate-quinone oxidoreductase) inhibitors, such as cyenopyrafen.…”

Mutations in the mitochondrial cytochrome b of Tetranychus urticae Koch (Acari: Tetranychidae) confer cross‐resistance between bifenazate and acequinocyl

“…Acequinocyl (AKD‐2023; 3‐dodecyl‐1,4‐dihydro‐1,4‐dioxo‐2‐naphthyl acetate) is presently the only commercialised acaricide of the naphthoquinone analogue group. It was discovered in the 1970s by DuPont,17 licensed to Agro Kanesho and commercialised in 1999 18–20. Acequinocyl is a proacaricide, and the deacetylated metabolite with a free hydroxy group is a powerful inhibitor of the Q o centre by acting as a structural analogue of ubiquinone 21.…”

Mode of action and pesticidal activity of the natural product dunnione and of some analogues

“…Extensive structure‐activity relationship studies resulted in the discovery of a range of novel pesticidal, and in particular insecticidal/miticidal, compounds that have been protected by four world‐wide families of patent applications 1. 3–5 They have been shown6, 7 to be respiratory inhibitors that act by inhibiting mitochondrial Complex III. The fungicidal properties of related 1,4‐naphthoquinones were investigated8 in detail at IACR‐Long Ashton during the 1970s; compounds with high levels of preventative activity but poor eradicant activity were identified.…”