Select small core structure carbamates exhibit high contact toxicity to "carbamate-resistant" strain malaria mosquitoes, Anopheles gambiae (Akron)

Wong, DM; Li, J; Chen, QH; Han, Q; Mutunga, JM; Wysinski, A; Anderson, TD; Ding, H; Carpenetti, TL; Verma, A; Islam, R; Paulson, SL; Lam, PC; Totrov, M; Bloomquist, JR; Carlier, PR

HERO ID

1787958

Reference Type

Journal Article

Year

2012

Language

English

PMID

23049714

HERO ID 1787958
In Press No
Year 2012
Title Select small core structure carbamates exhibit high contact toxicity to "carbamate-resistant" strain malaria mosquitoes, Anopheles gambiae (Akron)
Authors Wong, DM; Li, J; Chen, QH; Han, Q; Mutunga, JM; Wysinski, A; Anderson, TD; Ding, H; Carpenetti, TL; Verma, A; Islam, R; Paulson, SL; Lam, PC; Totrov, M; Bloomquist, JR; Carlier, PR
Journal PLoS ONE
Volume 7
Issue 10
Page Numbers e46712
Abstract Acetylcholinesterase (AChE) is a proven target for control of the malaria mosquito (Anopheles gambiae). Unfortunately, a single amino acid mutation (G119S) in An. gambiae AChE-1 (AgAChE) confers resistance to the AChE inhibitors currently approved by the World Health Organization for indoor residual spraying. In this report, we describe several carbamate inhibitors that potently inhibit G119S AgAChE and that are contact-toxic to carbamate-resistant An. gambiae. PCR-RFLP analysis was used to confirm that carbamate-susceptible G3 and carbamate-resistant Akron strains of An. gambiae carry wild-type (WT) and G119S AChE, respectively. G119S AgAChE was expressed and purified for the first time, and was shown to have only 3% of the turnover number (k(cat)) of the WT enzyme. Twelve carbamates were then assayed for inhibition of these enzymes. High resistance ratios (>2,500-fold) were observed for carbamates bearing a benzene ring core, consistent with the carbamate-resistant phenotype of the G119S enzyme. Interestingly, resistance ratios for two oxime methylcarbamates, and for five pyrazol-4-yl methylcarbamates were found to be much lower (4- to 65-fold). The toxicities of these carbamates to live G3 and Akron strain An. gambiae were determined. As expected from the enzyme resistance ratios, carbamates bearing a benzene ring core showed low toxicity to Akron strain An. gambiae (LC(50)>5,000 μg/mL). However, one oxime methylcarbamate (aldicarb) and five pyrazol-4-yl methylcarbamates (4a-e) showed good to excellent toxicity to the Akron strain (LC(50) = 32-650 μg/mL). These results suggest that appropriately functionalized "small-core" carbamates could function as a resistance-breaking anticholinesterase insecticides against the malaria mosquito.
Doi 10.1371/journal.pone.0046712
Pmid 23049714
Wosid WOS:000309388500041
Url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866997371&doi=10.1371%2fjournal.pone.0046712&partnerID=40&md5=e1fddcbd9adcbed2d6068d355f731115
Is Certified Translation No
Dupe Override No
Comments Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866997371&doi=10.1371%2fjournal.pone.0046712&partnerID=40&md5=e1fddcbd9adcbed2d6068d355f731115
Is Public Yes
Language Text English
Keyword acetylcholinesterase; aldicarb; bendiocarb; carbamic acid derivative; carbaril; carbofuran; cholinesterase inhibitor; genomic DNA; methomyl; oxime methylcarbamate derivative; propoxur; pyrazol 4 yl methylcarbamate derivative; recombinant enzyme; terbam; unclassified drug; Anopheles gambiae; article; controlled study; enzyme activity; enzyme analysis; enzyme inhibition; enzyme purification; female; genotype; insect control; LC 50; nonhuman; phenotype; polymerase chain reaction; protein expression; restriction fragment length polymorphism; synthesis; toxicity; wild type; Animals; Anopheles gambiae; Carbamates; Cholinesterase Inhibitors; Cholinesterases; Drug Resistance; Electrophoresis, Polyacrylamide Gel; Insect Vectors; Insecticides; Malaria; Molecular Structure; Mutation, Missense; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Anopheles gambiae
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