Potent and selective indole-based inhibitors targeting disease-transmitting mosquitoes
R. Rajeshwari, V. Duvauchelle, C. Lindgren, K. Stangner, S. Knutsson, N. Forsgren, F. Ekström, L. Kamau, A. Linusson
TL;DR
Researchers developed indole-based compounds that effectively target mosquito enzymes without harming humans, offering a new insecticide alternative.
Contribution
Indole-based compounds are shown to selectively inhibit mosquito acetylcholinesterase with high potency and low human toxicity.
Findings
26 indole-based compounds were synthesized and evaluated for AChE inhibition in mosquitoes and humans.
N-methylation improved potency, while bulkier benzyl groups enhanced selectivity over human AChE.
Four compounds showed strong insecticidal effects in live mosquitoes.
Abstract
Vector control with insecticides is an important preventive measure against mosquito-borne infectious diseases, such as malaria and dengue. The intensive usage of few insecticides has resulted in emerging resistance in mosquitoes, and unwanted off-target toxic effects. Therefore, there is great interest in alternative active ingredients. Here, we explore indole-based compounds as selective inhibitors against acetylcholinesterase 1 (AChE1) from the disease-transmitting mosquitoes Anopheles gambiae (An. gambiae, AgAChE1) and Aedes aegypti (Ae. aegypti, AeAChE1) as potential candidates for future insecticides used in vector control. Three sets of compounds were designed to explore their structure–activity relationship, and investigate their potentials regarding potency and selectivity. 26 indole-based compounds were synthesized and biochemically evaluated for inhibition against AgAChE1,…
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Taxonomy
TopicsCholinesterase and Neurodegenerative Diseases · Insect Pest Control Strategies · Enzyme function and inhibition