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dc.contributor.authorWong, Dawn M.en_US
dc.contributor.authorLi, Jianyongen_US
dc.contributor.authorChen, Qiao-Hongen_US
dc.contributor.authorHan, Qianen_US
dc.contributor.authorMutunga, James M.en_US
dc.contributor.authorWysinski, Aniaen_US
dc.contributor.authorAnderson, Troy D.en_US
dc.contributor.authorDing, Haizhenen_US
dc.contributor.authorCarpenetti, Tiffany L.en_US
dc.contributor.authorVerma, Asthaen_US
dc.contributor.authorIslam, Rafiqueen_US
dc.contributor.authorPaulson, Sally L.en_US
dc.contributor.authorLam, Polo Chun Hungen_US
dc.contributor.authorTotrov, Maximen_US
dc.contributor.authorBloomquist, Jeffrey R.en_US
dc.contributor.authorCarlier, Paul R.en_US
dc.date.accessioned2018-10-25T15:28:20Z
dc.date.available2018-10-25T15:28:20Z
dc.date.issued2012-10-01en_US
dc.identifier.othere46712en_US
dc.identifier.urihttp://hdl.handle.net/10919/85511
dc.description.abstractAcetylcholinesterase (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 (kcat) 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 (LC50>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 (LC50 = 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.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsCreative Commons Attribution 4.0 Internationalen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleSelect Small Core Structure Carbamates Exhibit High Contact Toxicity to "Carbamate-Resistant" Strain Malaria Mosquitoes, Anopheles gambiae (Akron)en_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0046712en_US
dc.identifier.volume7en_US
dc.identifier.issue10en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid23049714en_US
dc.identifier.eissn1932-6203en_US


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International