Open AccessAzido-Neonicotinoids as Candidate Photoaffinity Probes for Insect Nicotinic Acetylcholine Receptors [1]
Author(s) -
Peter Maienfisch,
Joerg Haettenschwiler,
Alfred Rindlisbacher,
Arnaud Decock,
Henning Wellmann,
Hartmut Kayser
Publication year - 2003
Publication title -
chimia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.387
H-Index - 55
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/000942903777678605
Subject(s) - clothianidin , thiamethoxam , imidacloprid , thiacloprid , spodoptera littoralis , neonicotinoid , nicotinic agonist , chemistry , stereochemistry , nicotinic acetylcholine receptor , aphis craccivora , photoaffinity labeling , biology , botany , biochemistry , receptor , pest analysis , aphididae , agronomy , pesticide , homoptera , noctuidae
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.