Neonicotinoid insecticides: Molecular features conferring selectivity for insect versus mammalian nicotinic receptors
Neonicotinoid insecticides: Molecular features conferring selectivity for insect versus mammalian nicotinic receptors
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DOI：
10.1021/jf000873c
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发表时间：
2000-12-01
影响因子：
6.1
通讯作者：
Casida, JE
中科院分区：
文献类型：
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作者：
Tomizawa, M;Lee, DL;Casida, JE
新烟碱类杀虫剂（此处以吡虫啉、噻虫啉和硝基亚甲基类似物为代表）对昆虫与哺乳动物的选择性毒性是其三种N-未取代亚胺衍生物或尼古丁或皮巴替丁所不具备的。相同的选择性模式在受体水平上很明显，即独立测定的昆虫烟碱乙酰胆碱受体 (nAChR) 与哺乳动物 nAChR 亚型（α1、α3、α4 和 α7）。昆虫选择性化合物不被硝基亚胺、氰基亚胺或硝基亚甲基质子化，而哺乳动物选择性化合物在生理pH下电离。我们提出，硝基或氰基的带负电荷的尖端（不是前面提到的咪唑烷 N-1 上的部分正电荷）与昆虫 nAChR 的假定阳离子亚位点相互作用。这与哺乳动物 nAChR 形成对比，其中新烟碱类亚胺衍生物的亚胺阳离子 (C+-NH2 C =+NH2) 或尼古丁或皮巴替丁的铵氮与阴离子亚位点相互作用。
The favorable selective toxicity of neonicotinoid insecticides (represented here by imidacloprid, thiacloprid, and a nitromethylene analogue) for insects versus mammals is not shared by three of their N-unsubstituted imine derivatives or by nicotine or epibatidine. The same selectivity pattern is evident at the receptor level, i.e., the insect nicotinic acetylcholine receptor (nAChR) versus mammalian nAChR subtypes (alpha1, alpha3, alpha4, and alpha7) assayed independently. The insect-selective compounds are not protonated with a nitroimine, cyanoimine, or nitromethylene group and the mammalian-selective compounds are ionized at physiological pH. We propose that the negatively charged tip of the nitro or cyano group (not a partial positive charge at imidazolidine N-1 as suggested earlier) interacts with a putative cationic subsite of the insect nAChR. This contrasts with the mammalian nAChRs where the iminium cation (C+-NH2 C =+NH2) of the neonicotinoid imine derivatives or ammonium nitrogen of nicotine or epibatidine interacts with the anionic subsite.