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Tariquidar derivatives have been described as potent and selective ABCG2 inhibitors. However, their susceptibility to hydrolysis limits their applicability. The current study comprises the synthesis and characterization of novel tariquidar-related inhibitors, obtained by bioisosteric replacement of the labile moieties in our previous tariquidar analog UR-ME22-1 (9). CuAAC ("click" reaction) gave convenient access to a triazole core as a substitute for the labile amide group and the labile ester moiety was replaced by different acyl groups in a Sugasawa reaction. A stability assay proved the enhancement of the stability in blood plasma. Compounds UR-MB108 (57) and UR-MB136 (59) inhibited ABCG2 in a Hoechst 33342 transport assay with an IC50 value of about 80 nM and belong to the most potent ABCG2 inhibitors described so far. Compound 57 was highly selective, whereas its PEGylated analog 59 showed some potency at ABCB1. Both 57 and 59 produced an ABCG2 ATPase-depressing effect which is in agreement with our precedent cryo-EM study identifying 59 as an ATPase inhibitor that exerts its effect via locking the inward-facing conformation. Thermostabilization of ABCG2 by 57 and 59 can be taken as a hint to comparable binding to ABCG2. As reference substances, compounds 57 and 59 allow additional mechanistic studies on ABCG2 inhibition. Due to their stability in blood plasma, they are also applicable in vivo. The highly specific inhibitor 57 is suited for PET labeling, helping to further elucidate the (patho)physiological role of ABCG2, e.g. at the BBB.

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ABC transporters, including ABCG2, play a vital role in defending the human body against the vast range of xenobiotics. Even though this is beneficial for human health, these protein transporters have been implicated in the emerging resistance of cancer cells to a variety of structurally and functionally diverse anticancer drugs. In order to investigate their role in resistance, potent and selective ABCG2 modulators have been described in the literature. A leading class of modulators are the tariquidar analogues; however, their susceptibility to hydrolysis limits their applicable use. To overcome this, we synthesized a novel series of chalcone- and ketone-based compounds inspired by reported tariquidar analogues. Compounds were characterized and evaluated for their ABCG2 modulatory activity and ABC transporter selectivity. When compared to transporters ABCB1 and ABCC1, the chalcone-based compounds exhibited selectivity for ABCG2, while the ketone-based compounds showed only a slight preference for ABCG2. From the former series, chalcone 16d (UR-DP48) displayed similar activity to the reference fumitremorgin C, both producing comparable maximal effects. The compound exhibited marked antiproliferative activity, while cytotoxicity was less pronounced for the most active compound 17f from the ketone series. Chalcone-containing tariquidar analogues are promising modulators to aid in functional investigations of ABCG2 transporters.

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A field experiment of 4 years' duration was carried out to evaluate the efficacy of combining the mating disruption (MD) formulation Dismate ZETA ((9Z,12E)-tetradecadienyl acetate), with the parasitoid Habrobracon hebetor against the Indianmeal moth Plodia interpunctella in a chocolate factory. The experimental period began early in 2011 and ended in late 2014. Begane Dismate dispensers were placed in the facility from 2011 to 2014 and H. hebetor was released in 2014. Pheromone-baited traps were used to monitor the flight activity of the male moths and oviposition Petri dish traps were placed to assess the progeny production of P. interpunctella females. Following the start of MD, a decrease in the number of P. interpunctella males caught in monitoring traps was observed from 2011 to 2013. A further decline in the moth population was noted in 2014, when MD was combined with the release of parasitoids. The presence of larvae in the oviposition cups was occasionally observed throughout the monitoring period, from 2011 to 2014. This study demonstrates that the combined system of MD and parasitoids is an effective and reliable technique that can be used to successfully control P. interpunctella.

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Although some species of Cryptocephalinae (Coleoptera: Chrysomelidae) have been documented with ants (Hymenoptera: Formicidae) for almost 200 years, information on this association is fragmentary. This contribution synthesizes extant literature and analysizes the data for biological patterns. Myrmecophily is more common in the tribe Clytrini than in Cryptocephalini, but not documented for Fulcidacini or the closely-related Lamprosomatinae. Myrmecophilous cryptocephalines (34 species in 14 genera) primarily live among formicine and myrmecines ants as hosts. These two ant lineages are putative sister-groups, with their root-node dated to between 77-90 mya. In the New World tropics, the relatively recent radiation of ants from moist forests to more xeric ecosystems might have propelled the association of cryptocephalines and ant nests. Literature records suggest that the defensive behavioral profile or chemical profile (or both) of these ants has been exploited by cryptocephalines. Another pattern appears to be that specialized natural enemies, especially parasitoid Hymenoptera, exploit cryptocephaline beetles inside the ant nests. With the extant data at hand, based on the minimum age of a fossil larva dated to 45 mya, we can infer that the origin of cryptocephaline myrmecophily could have arisen within the Upper Cretaceous or later. It remains unknown how many times myrmecophily has appeared, or how old is the behavior. This uncertainty is compounded by incongruent hypotheses about the origins of Chrysomelidae and angiosperm-associated lineages of cryptocephalines. Living with ants offers multiple advantages that might have aided the colonization of xeric environments by some cryptocephaline species.

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Three species of trichogrammatid egg parasitoids (Trichogramma deion Pinto & Oatman, Trichogramma ostriniae Pang & Chen, and Trichogramma pretiosum Riley) (Hymenoptera: Trichogrammatidae) were evaluated under laboratory conditions as potential biological control agents for the Indianmeal moth, Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae), on retail shelves. A single shelving unit was used in each trial and a grid of sentinel egg disks was used to evaluate foraging success. The shelving consisted of pallet units with five shelves that were either bare or stocked with empty cereal boxes. In each replicate, approximately 500 female Trichogramma were released at the center of the shelving unit and allowed to forage for 48 h. Percentage of egg parasitism and percentage of host egg mortality were recorded after 7 d. Foraging success as well as the spatial pattern of parasitism differed significantly among the three Trichogramma species. Percentage of egg parasitism was approximately 4 times greater for T. deion than for T. ostriniae or T. pretiosum. The vertical distribution of parasitism by T. deion was also more uniform than for the other two species. In addition, the presence of packaging affected the foraging efficiency of T. ostriniae and T. pretiosum but not T. deion. Based on these findings, Trichogramma deion may be the best-suited candidate for augmentative biological control of P. interpunctella in retail stores, and a central release point of T. deion will likely provide adequate coverage of products on pallet-type shelving.

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