Department of Biological Sciences, Smith College, Northampton, MA.
Neuroscience Program, Smith College, Northampton, MA.
J Med Entomol. 2020 Jul 4;57(4):1032-1040. doi: 10.1093/jme/tjaa010.
The carboxamide N,N-di-ethyl-meta-toluamide (DEET) is the most effective and widely used insect repellent today. However, drawbacks concerning the efficacy and the safety of the repellent have led to efforts to design new classes of insect repellents. Through quantitative structure-activity relationships, chemists have discovered two chemical groups of novel repellents: the acylpiperidines and the carboxamides, with the acylpiperidines generally more potent in biological assays. Although the exact mechanism of action of DEET and other repellents has not yet been thoroughly elucidated, previous research shows that the activity of insect odorant receptors are inhibited in the presence of repellents. The present electrophysiological study employs two-electrode voltage clamp with Xenopus laevis oocytes expressing AgOR2/AgOrco and AgOR8/AgOrco receptors to assess the effects of the novel repellents on Anopheles gambiae Giles (Insecta: Diptera: Culicidae) mosquito odorant receptors. The novel acylpiperidines and carboxamides reversibly inhibited (12-91%) odorant-evoked currents from both AgOR2/AgOrco and AgOR8/AgOrco receptors in a dose-dependent manner at all tested concentrations (30 μM to 1 mM). Furthermore, all the novel agents were more potent inhibitors of the receptors than DEET, with the acylpiperidines producing on average greater inhibition than the carboxamides. Interestingly, there was a correlation (r2 = 0.72) between the percentage inhibition of AgOR2/AgOrco receptor currents and protection times of the acylpiperidines. Our results add to existing evidence that the repellency of a compound is linked to its ability to disrupt the insect olfactory system and that the acylpiperidines could represent a class of more effective alternatives to the current gold standard, DEET.
N,N-二乙基间甲苯甲酰胺（DEET）是当今最有效、应用最广泛的昆虫驱避剂。然而，驱避剂的功效和安全性存在一些缺陷，促使人们努力设计新的驱避剂类别。通过定量构效关系，化学家发现了两类新型驱避剂：酰基哌啶和酰胺，其中酰基哌啶在生物测定中通常更有效。尽管 DEET 和其他驱避剂的确切作用机制尚未得到彻底阐明，但先前的研究表明，昆虫气味受体的活性在驱避剂存在的情况下受到抑制。本电生理学研究采用双电极电压钳技术，使用表达 AgOR2/AgOrco 和 AgOR8/AgOrco 受体的非洲爪蟾卵母细胞，评估新型驱避剂对冈比亚按蚊（节肢动物门：双翅目：蚊科）气味受体的影响。新型酰基哌啶和酰胺可在所有测试浓度（30 μM 至 1 mM）下，以剂量依赖的方式可逆抑制 AgOR2/AgOrco 和 AgOR8/AgOrco 受体的气味诱导电流（12-91%）。此外，与 DEET 相比，所有新型试剂均为更有效的受体抑制剂，其中酰基哌啶的抑制作用平均大于酰胺。有趣的是，AgOR2/AgOrco 受体电流的抑制百分比与酰基哌啶的保护时间之间存在相关性（r2 = 0.72）。我们的研究结果进一步证明了化合物的驱避性与其破坏昆虫嗅觉系统的能力有关，并且酰基哌啶可能代表比目前的黄金标准 DEET 更有效的替代类别。
