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Mosquito Acetylcholinesterase as a Target for Novel Phenyl-Substituted Carbamates

Emerging Pathogens Institute, Entomology and Nematology Department, University of Florida, Gainesville, FL 32610, USA
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
Molsoft LLC, 11199 Sorrento Valley Road, S209 San Diego, CA 92121, USA
Author to whom correspondence should be addressed.
Current Address: Department of Entomology, US Army Medical Research Directorate-Africa, Kenya, KEMRI CGHR, P.O. Box 54-40100, Kisumu, Kenya.
Int. J. Environ. Res. Public Health 2019, 16(9), 1500;
Received: 26 February 2019 / Revised: 23 April 2019 / Accepted: 24 April 2019 / Published: 28 April 2019
(This article belongs to the Special Issue Mosquito-Borne Disease)
New insecticides are needed for control of disease-vectoring mosquitoes and this research evaluates the activity of new carbamate acetylcholinesterase (AChE) inhibitors. Biochemical and toxicological characterization of carbamates based on the parent structure of terbam, 3-tert-butylphenyl methylcarbamate, was performed. In vitro enzyme inhibition selectivity (Anopheles gambiae versus human) was assessed by the Ellman assay, as well as the lethality to whole insects by the World Health Organization (WHO) paper contact assay. Bromination at the phenyl C6 position increased inhibitory potency to both AChEs, whereas a 6-iodo substituent led to loss of potency, and both halogenations caused a significant reduction of mosquitocidal activity. Similarly, installation of a hexyl substituent at C6 drastically reduced inhibition of AgAChE, but showed a smaller reduction in the inhibition of hAChE. A series of 4-carboxamido analogs of the parent compound gave reduced activity against AgAChE and generally showed more activity against hAChE than AgAChE. Replacement of the 3-t-buyl group with CF3 resulted in poor anticholinesterase activity, but this compound did have measurable mosquitocidal activity. A series of methyl- and fluoro- analogs of 3-trialkylsilyl compounds were also synthesized, but unfortunately resulted in disappointing activity. Finally, a series of sulfenylated proinsecticides showed poor paper contact toxicity, but one of them had topical activity against adult female Anopheles gambiae. Overall, the analogs prepared here contributed to a better understanding of carbamate structure–activity relationships (SAR), but no new significant leads were generated. View Full-Text
Keywords: Anopheles gambiae; anticholinesterase; insecticide; toxicity Anopheles gambiae; anticholinesterase; insecticide; toxicity
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MDPI and ACS Style

Mutunga, J.M.; Ma, M.; Chen, Q.-H.; Hartsel, J.A.; Wong, D.M.; Ding, S.; Totrov, M.; Carlier, P.R.; Bloomquist, J.R. Mosquito Acetylcholinesterase as a Target for Novel Phenyl-Substituted Carbamates. Int. J. Environ. Res. Public Health 2019, 16, 1500.

AMA Style

Mutunga JM, Ma M, Chen Q-H, Hartsel JA, Wong DM, Ding S, Totrov M, Carlier PR, Bloomquist JR. Mosquito Acetylcholinesterase as a Target for Novel Phenyl-Substituted Carbamates. International Journal of Environmental Research and Public Health. 2019; 16(9):1500.

Chicago/Turabian Style

Mutunga, James M., Ming Ma, Qiao-Hong Chen, Joshua A. Hartsel, Dawn M. Wong, Sha Ding, Max Totrov, Paul R. Carlier, and Jeffrey R. Bloomquist 2019. "Mosquito Acetylcholinesterase as a Target for Novel Phenyl-Substituted Carbamates" International Journal of Environmental Research and Public Health 16, no. 9: 1500.

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