Pyrrole-2 carboxamides - A novel class of insect ryanodine receptor activators.

The ryanodine receptor (RyR) is an intracellular calcium channel critical to the regulation of insect muscle contraction and the target site of diamide insecticides such as chlorantraniliprole, cyantraniliprole and flubendiamide. To-date, diamides are the only known class of synthetic molecules with high potency against insect RyRs. Target-based screening of an informer library led to discovery of a novel class of RyR activators, pyrrole-2-carboxamides.

Mesoionic insecticides: a novel class of insecticides that modulate nicotinic acetylcholine receptors.

Background: As the world population grows towards 9 billion by 2050, it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields owing to pests. The development of new insecticides will help to sustain this protection and overcome insecticide resistance.

Synthetic atpenin analogs: Potent mitochondrial inhibitors of mammalian and fungal succinate-ubiquinone oxidoreductase.

Atpenins and harzianopyridone represent a unique class of penta-substituted pyridine-based natural products that are potent inhibitors of complex II (succinate-ubiquinone oxidoreductase) in the mitochondrial respiratory chain. These compounds block electron transfer in oxidative phosphorylation by inhibiting oxidation of succinate to fumarate and the coupled reduction of ubiquinone to ubiquinol. From our investigations of complex II inhibitors as potential agricultural fungicides, we report here on the synthesis and complex II inhibition for a series of synthetic atpenin analogs against both mammalian and fungal forms of the enzyme.

Ion channels: molecular targets of neuroactive insecticides.

Many of the insecticides in current use act on molecular targets in the insect nervous system. Recently, our understanding of these targets has improved as a result of the complete sequencing of an insect genome, i.e.

Bicuculline-insensitive GABA-gated Cl- channels in the larval nervous system of the moth Manduca sexta.

GABA-gated Cl(-) channels were studied in the nervous system of the larval tobacco hawk moth, Manduca sexta, using electrophysiology, (36)Cl(-) uptake into membrane microsacs and immunocytochemistry. A GABA-induced increase in Cl(-) conductance was recorded from a visually identifiable neurone ( fg1) in the desheathed frontal ganglion. The response was insensitive to the vertebrate GABA(A) receptor antagonist, bicuculline, but was blocked by picrotoxinin.

In vitro neuropharmacological evaluation of piperovatine, an isobutylamide from Piper piscatorum (Piperaceae).

Piperovatine, a sialogogic, piscicidal, and buccal local anesthesia producing isobutyl amide from the amazonian piscicidal and toothache-relieving plant, Piper piscatorum Trelease et Yuncker (Piperaceae), was evaluated for its ability to induce changes in neuronal intracellular calcium concentration. Ratiometric calcium imaging of Periplaneta americana neuronal cell cultures upon piperovatine application revealed that this compound induced dramatic increases in intracellular calcium concentration. Calcium flux was not affected by co-application of the muscarinic acetylcholine receptor antagonist, atropine, indicating that the parasympathomimetic system was not involved in piperovatine's sialogogic actions.

Tricyclic cyanoguanidines: synthesis, site of action and insecticidal activity of a novel class of reversible acetylcholinesterase inhibitors.

Bridged-tricyclic cyanoguanidines 1 were found to be active as insecticides. The preparation and structure-activity relationships of oxacyclic (X=O) and carbocyclic (X=CH(2)) analogues of 1 is described. Compounds 1 were found to inhibit acetylcholinesterase with IC(50) values comparable to the organophosphate Paraoxon.