The use of substituted alkynyl phenoxy derivatives of piperonyl butoxide to control insecticide-resistant pests.

BACKGROUND: Derivatives of piperonyl butoxide with alkynyl side chains were tested in vitro and in vivo against pyrethroid-resistant Meligethes aeneus and imidacloprid-resistant Myzus persicae. RESULTS: Synergists with the alkynyl side chain were more effective inhibitors of P450 activity in vitro than piperonyl butoxide, and demonstrated high levels of synergism in vivo, with up to 290-fold synergism of imidacloprid against imidacloprid-resistant M. persicae. CONCLUSIONS: These 'second-generation' synergists could overcome metabolic resistance in many pest species and possibly enable reduced rates of insecticide application in some cases. © 2016 Society of Chemical Industry.

The interactions between piperonyl butoxide and E4, a resistance-associated esterase from the peach-potato aphid, Myzus persicae Sulzer (Hemiptera: Aphididae).

BACKGROUND: It has been reported previously that piperonyl butoxide (PBO) can inhibit both P450 and esterase activity. Although the method by which PBO combines with cytochrome P450 has been identified, the way in which it acts as an esterase inhibitor has not been established. This paper characterises the interactions between PBO and the resistance-associated esterase in Myzus persicae, E4. RESULTS: After incubation with PBO/analogues, hydrolysis of 1-naphthyl acetate by E4 is increased, but sequestration of azamethiphos is reduced. Rudimentary in silico modelling suggests PBO docks at the lip of the aromatic gorge. CONCLUSIONS: PBO binds with E4 to accelerate small substrates to the active-site triad, while acting as a blockade to larger, insecticidal molecules. Structure-activity studies with analogues of PBO also reveal the essential chemical moieties present in the molecule.

The effect of a piperonyl butoxide/tau-fluvalinate mixture on pollen beetle (Meligethes aeneus) and honey bees (Apis mellifera).

BACKGROUND: Previous work has characterised pyrethroid resistance in pollen beetle (Meligethes aeneus F.) as principally an oxidative mechanism. Piperonyl butoxide (PBO) can synergise this resistance in the field, but its effects on the honey bee are thought to be unacceptable. RESULTS: A field trial in Poland was conducted to show that a mixture of PBO and tau-fluvalinate at the registered rate gave increased and longer-lasting control of resistant pollen beetle. Four days after spraying with tau-fluvalinate, only 20% of pollen beetles were controlled, compared with 70% if the tau-fluvalinate/PBO mixture was used. No detriment to honey bee health was observed using the same mixture. CONCLUSIONS: PBO, if used in conjunction with a pyrethroid of relatively low bee toxicity, can successfully overcome pyrethroid resistance in pollen beetle without incurring an increased loss of honey bees, even if they are present at the time of spraying.

Characterising metabolic resistance in pyrethroid-insensitive pollen beetle (Meligethes aeneus F.) from Poland and Switzerland.

BACKGROUND: Pollen beetle (Meligethes aeneus F.) has become the most important pest of oilseed rape in Europe, but its control has been greatly hindered by pyrethroid resistance. Target-site resistance has been implicated previously, and, whilst synergism has been found with piperonyl butoxide (PBO), the exact nature of metabolic resistance has remained unknown. The use of PBO, in conjunction with its analogue EN 16/5-1, has allowed the characterisation of metabolic resistance. RESULTS: In vitro assays in combination with in vivo studies using PBO and EN 16/5-1 showed that high synergism of pyrethroids was primarily correlated with an oxidative mechanism, although a limited contribution by esterases was implicated in one population. CONCLUSION: Differential synergism has enabled the characterisation of pyrethroid resistance in populations of M. aeneus. It was found to be principally due to an oxidative-based mechanism, and, if a synergist were to be used to inhibit this enzyme group, renewed control against resistant pests could be achieved.

Metabolic enzyme(s) confer imidacloprid resistance in a clone of Myzus persicae (Sulzer) (Hemiptera: Aphididae) from Greece.

BACKGROUND: Previous studies have reported varying levels of resistance against imidacloprid in several insect species, including populations of the peach-potato aphid, Myzus persicae (Sulzer). These cases of resistance have been attributed to either target-site resistance or enhanced detoxification. In this study, a clone of M. persicae originating from Greece revealed a 60-fold resistance factor to imidacloprid. RESULTS: The Greek clone is compared in terms of metabolic enzyme activity and synergism profiles with other M. persicae clones showing lower imidacloprid resistance. CONCLUSION: A combination of in vitro biochemical assays and in vivo differential synergism studies using PBO and a close analogue EN 16/5-1 suggests that the mechanism conferring increased resistance in this clone is primarily due to enhanced oxidase activity.

An analogue of piperonyl butoxide facilitates the characterisation of metabolic resistance.

BACKGROUND: Previous work has demonstrated that piperonyl butoxide (PBO) not only inhibits microsomal oxidases but also resistance-associated esterases. The ability to inhibit both major metabolic resistance enzymes makes it an ideal synergist to enhance xenobiotics but negates the ability to differentiate which enzyme group is responsible for conferring resistance. RESULTS: This study examines an analogue that retains the ability to inhibit esterases but is restricted in its ability to act on microsomal oxidases, thus allowing an informed decision on resistance enzymes to be made when used in conjunction with the parent molecule. CONCLUSION: Using examples of resistant insects with well-characterised resistance mechanisms, a combination of PBO and analogue allows identification of the metabolic mechanism responsible for conferring resistance. The relative potency of PBO as both an esterase inhibitor and an oxidase inhibitor is also discussed.