Select small core structure carbamates exhibit high contact toxicity to "carbamate-resistant" strain malaria mosquitoes, Anopheles gambiae (Akron).
Select small core structure carbamates exhibit high contact toxicity to "carbamate-resistant" strain malaria mosquitoes, Anopheles gambiae (Akron).
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DOI：
10.1371/journal.pone.0046712
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Carlier PR
中科院分区：
文献类型：
--
作者：
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
乙酰胆碱酯酶（AChE）是一个被证明的控制疟疾蚊子（冈比亚按蚊）的目标。不幸的是，一个单一的氨基酸突变（G119 S）在An。冈比亚AChE-1（AgAChE）赋予对目前被世界卫生组织批准用于室内滞留喷洒的AChE抑制剂的抗性。在这份报告中，我们描述了几种氨基甲酸酯抑制剂，有效地抑制G119 S AgAChE和接触毒性的氨基甲酸酯耐药性安。冈比亚。采用PCR-RFLP分析方法，证实氨基甲酸酯敏感株G3和氨基甲酸酯耐药株Akron。冈比亚分别携带野生型（WT）和G119 S AChE。G119 S AgAChE首次被表达和纯化，并且显示仅具有WT酶的周转数（kcat）的3%。然后测定12种氨基甲酸酯对这些酶的抑制作用。观察到带有苯环核心的氨基甲酸酯的耐药率很高（> 2，500倍），这与G119 S酶的氨基甲酸酯耐药表型一致。有趣的是，发现两种肟甲基氨基甲酸酯和五种吡唑-4-基甲基氨基甲酸酯的耐药率要低得多（4至65倍）。这些氨基甲酸酯类化合物对G3和Akron菌株An.冈比亚的决定。如从酶抗性比率所预期的，具有苯环核心的氨基甲酸酯对阿克伦菌株An显示出低毒性。冈比亚（LC 50> 5，000 μg/mL）。然而，一种甲基氨基甲酸肟酯（涕灭威）和五种甲基氨基甲酸吡唑-4-基酯（4a-e）对Akron菌株显示出良好至极好的毒性（LC 50 = 32-650 μg/mL）。 这些结果表明，适当官能化的“小核”氨基甲酸酯可以作为一种破坏抗药性的抗胆碱酯酶杀虫剂对疟疾蚊子。
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 (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.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
DOI：
10.1016/j.cbpb.2008.03.008
发表时间：
2008-07-01
影响因子：
2.2
作者：
Alout, Haoues;Djogbenou, Luc;Weill, Mylene
通讯作者：
Weill, Mylene
影响因子：
4.7
作者：
Bourguet, D;Raymond, M;Arpagaus, M
通讯作者：
Arpagaus, M
影响因子：
4.8
作者：
Bourne, Yves;Radic, Zoran;Marchot, Pascale
通讯作者：
Marchot, Pascale
影响因子：
5.1
作者：
Geyer, BC;Muralidharan, M;Mor, TS
通讯作者：
Mor, TS