Azido-Neonicotinoids as Candidate Photoaffinity Probes for Insect Nicotinic Acetylcholine Receptors [1]


  • Peter Maienfisch
  • Joerg Haettenschwiler
  • Alfred Rindlisbacher
  • Arnaud Decock
  • Henning Wellmann
  • Hartmut Kayser



Azido-neonicotinoids, Candidate photoaffinity probes, Imidacloprid, Insecticidal activity, Insecticides, Neonicotinoids, Nicotinic acetylcholine receptors, Thiamethoxam


The neonicotinoids are the most successful chemical class of insecticides reaching sales of more than 630 Mio $ in 2001, mainly due to the excellent market performance of imidacloprid and thiamethoxam. The insect nicotinic acetylcholine receptors (nAChRs) are the targets for these compounds, which are highly effective against a variety of sucking and chewing insects. Compared with the other neonicotinoid sales products, thiamethoxam binds in a different way, possibly to a different site of nAChRs in aphids. To gain further insight into the different modes of binding, a research program applying the photoaffinity labeling technique was started. A series of novel candidate photoaffinity probes containing a 5-azido-6-chloropyridin-3-ylmethyl group were prepared from 5-azido-6-chloropyridin-3-ylmethyl chloride, which was obtained in three steps from 6-chloropyridin-3-ylmethyl chloride. These probes showed good to excellent contact/feeding and systemic activity against Myzus persicae, however, they were at least 4- to 16-fold less effective against Aphis craccivora, Nilaparvata lugens, Spodoptera littoralis, and Diabrotica balteata than the neonicotinoid sales products. In general, the introduction of an azide group at C(5) of the 6-chloropyridin-3-ylmethyl substituent resulted in reduced potency as well as in a narrower pest spectrum. In competition binding assays with [3H]imidacloprid, analogues of imidacloprid, clothianidin, thiacloprid and thiamethoxam containing a 5-azido-6-chloropyridin-3-ylmethyl group showed high displacing potency with nAChRs from Aphis and Myzus (Ki values: 2 to 27 nM) suggesting that these compounds are valuable candidate photoaffinity probes. Taking into account the biological screening activity as well as the receptor binding potency, 1-(5-azido-6-chloropyridin-3-ylmethyl)-2-nitroimino-imidazolidine, N-(5-azido-6-chloropyridin-3-ylmethyl)-N?-methyl-N?-nitroguanidine and 3-(5-azido-6-chloropyridin-3-ylmethyl)-2-cyanoimino-thiazolidine were identified as the preferred candidate neonicotinoid photoaffinity probes to study the imidacloprid binding site.




How to Cite

P. Maienfisch, J. Haettenschwiler, A. Rindlisbacher, A. Decock, H. Wellmann, H. Kayser, Chimia 2003, 57, 710, DOI: 10.2533/000942903777678605.



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