Currently available insecticide-treated nets (ITNs) are losing efficacy due to emerging resistance of Anopheline mosquitoes to the pyrethroid insecticides impregnated on these nets. Anticholinesterase inhibitors that are highly selective for An. gambiae acetylcholinesterase (AChE) could replace or supplement pyrethroids on ITNs if low mammalian toxicity could be demonstrated. In addition, new anticholinesterases that show toxicity to G119S AChE carbamate-resistant mosquitoes could be very useful for ITNs or indoor residual spraying. In this presentation we will review the structural determinants of inhibition selectivity and potency of a wide series of carbamates to wild-type (WT) and G119S An. gambiae AChE. A ligand-based in silico model that offers good predictive power for An. gambiae/human inhibition selectivity will be presented. Current efforts to combine high An. gambiae/human selectivity with good contact toxicity towards WT and G119S-bearing mosquitoes will be reviewed, as will preliminary mouse oral toxicity of promising candidates.

Designing anticholinesterase insecticides to achieve high selectivity for the malaria mosquito, <i>Anopheles gambiae</i>, and potency against known resistance mutations

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Designing anticholinesterase insecticides to achieve high selectivity for the malaria mosquito, Anopheles gambiae, and potency against known resistance mutations