Pro-insecticides have been a significant part of the insecticide market for decades.  Bio-activation of such compounds is an enzyme-controlled process, where the target insect is able to metabolize the pro-form into an active compound.  This approach has several recognized advantages, including the possibility of the pro-form having superior bio-kinetic properties than the insecticide form, which can enable the applied compound to be delivered to the insect target before being activated. In the best applications, the target insect is better able to activate the applied compound to the drug form relative to non-target organisms, which may lead to an increased safety factor.  A less recognized advantage of pro-insecticides could be overcoming insecticide resistance. Similar to pro-insecticide activation, metabolic mechanisms of insecticide resistance are also enzymatic processes. The literature shows that pro-insecticides can be more, less, or similarly active compared to non-activated insecticides.  This reflects the differential activity of the enzymes of resistant strains, which can lead to enhanced bio-activation in some cases, or de-activation if the site of metabolism is different from the site of activation.  One BASF pro-insecticide has been shown to be more effective on certain resistant insect strains compared to susceptible strains. This was not an intentional part of the molecular design, but a fortunate result of its natural bioactivation pathway.  In the past 15 years, since the identification of CYP6G1 as an important isoform in the development of resistance in <i>Drosophila</i>, there has been a dramatic increase in the knowledge of the specific enzymes which confer metabolic resistance in multiple insect strains.  With this greater understanding, it should be possible to better design future pro-insecticides to be preferentially activated by the very enzymes which lead to insecticide resistance.  This approach has the potential to lead to pro-insecticides with negative cross resistance profiles. <br/>

Proinsecticides as potential resistance management tools

2019 Fall National Meeting

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