N'-mono- and N, N'-diacyl derivatives of benzyl and arylhydrazines as contact insecticides against adult Anopheles gambiae.

New public health insecticides are urgently required to prevent the spread of vector-borne disease. With the goal of identifying new K+-channel-directed mosquitocides, analogs of the RH-5849 family of diacyl t-butylhydrazines were synthesized and tested for topical toxicity against adult Anopheles gambiae, the African vector of malaria. In total, 80N'-monoacyl and N, N'-diacyl derivatives of benzyl- and arylhydrazines were prepared. Three compounds (2bo, 2kb, 3ab) were identified that were more toxic than RH-5849 and RH-1266. The potencies of these compounds to block K+ currents in An. gambiae and human Kv2.1 channels were assessed to address their possible mechanism of mosquitocidal action. Selectivity for inhibition of An. gambiae Kv2.1 vs human Kv2.1 did not exceed 3-fold. Furthermore, no correlation was seen between the potency of insecticidal action and K+ channel blocking potency. These observations, combined with the minimal knockdown seen with 2bo near its LD50 value, suggests a mode of action outside of the nervous system.

Interaction of plant essential oil terpenoids with the southern cattle tick tyramine receptor: A potential biopesticide target.

An outbreak of the southern cattle tick, Rhipicephalus (Boophilus) microplus, (Canestrini), in the United States would have devastating consequences on the cattle industry. Tick populations have developed resistance to current acaricides, highlighting the need to identify new biochemical targets along with new chemistry. Furthermore, acaricide resistance could further hamper control of tick populations during an outbreak. Botanically-based compounds may provide a safe alternative for efficacious control of the southern cattle tick. We have developed a heterologous expression system that stably expresses the cattle tick's tyramine receptor with a G-protein chimera, producing a system that is amenable to high-throughput screening. Screening an in-house terpenoid library, at two screening concentrations (10 µM and 100 µM), has identified four terpenoids (piperonyl alcohol, 1,4-cineole, carvacrol and isoeugenol) that we believe are positive modulators of the southern cattle tick's tyramine receptor.

The phenolic monoterpenoid carvacrol inhibits the binding of nicotine to the housefly nicotinic acetylcholine receptor.

BACKGROUND: The phenolic monoterpenoid carvacrol, which is found in many plant essential oils (thyme, oregano and Alaska yellow cedar), is highly active against pest arthropods, but its mechanisms of action are not fully understood. Here, carvacrol is shown to bind in a membrane preparation containing insect nicotinic acetylcholine receptors (nAChRs). [(14) C]-Nicotine binding assays with Musca domestica (housefly) nAChRs were used in this study to demonstrate carvacrol's binding to nAChRs, thereby acting as a modulator of the receptors. RESULTS: Carvacrol showed a concentration-dependent inhibition of [(14) C]-nicotine binding in a membrane preparation of housefly heads containing nAChRs, with IC50 = 1.4 µM, in a non-competitive pattern. Binding studies with neonicotinoid insecticides revealed that imidacloprid and thiamethoxam did not inhibit the binding of [(14) C]-nicotine, while dinotefuran, from the guanidine subclass of neonicotinoids, inhibited nicotine binding like carvacrol. CONCLUSIONS: Carvacrol binds to housefly nAChRs at a binding site distinct from nicotine and acetylcholine, and the nAChRs are a possible target of carvacrol for its insecticidal activity.