Malaria causes nearly one million deaths every year, of which 91% are in Africa. Insecticide-treated nets (ITNs) provide the first line of defense against malaria transmission in malaria-endemic countries. At present only pyrethroid insecticides are approved by WHOPES for use on ITNs, but the emergence of pyrethroid resistant strains of Anopheles gambiae has jeopardized this disease control method. Our goal is to identify a new class of insecticides that will be safe to be deployed on ITNs. An additional design goal is to inhibit the G119S resistant mutant of the mosquito enzyme and at the same time to achieve selectivity for inhibition of An. gambiae acetycholinesterase (AgAChE) over the human acetycholinesterase (hAChE). We have discovered that selected five-membered ring heterocyclic carbamates and carboxamides show good contact toxicity to both wild-type and G119S resistant malaria mosquitoes. Variation in the ring substituent can lead to good selectivity for AgAChE over hAChE.

Five-membered ring heterocyclic carbamates and carboxamides: The quest for resistance-breaking, species-selective acetylcholinesterase inhibitors against the malaria mosquito

244th National Meeting (2012)

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