Ohno_2009_Chem.Res.Toxicol_22_476

Reference

Title : Molecular features of neonicotinoid pharmacophore variants interacting with the insect nicotinic receptor - Ohno_2009_Chem.Res.Toxicol_22_476
Author(s) : Ohno I , Tomizawa M , Durkin KA , Naruse Y , Casida JE , Kagabu S
Ref : Chemical Research in Toxicology , 22 :476 , 2009
Abstract :

Molecular interactions of neonicotinoid insecticides with the nicotinic acetylcholine receptor have been mapped by chemical and structural neurobiology approaches, thereby encouraging the biorational design of novel nicotinic ligands. This investigation designs, prepares, and evaluates the target site potency of neonicotinoid analogues with various types of electronegative pharmacophores and subsequently predicts their molecular recognition in the ligand-binding pocket. The N-nitroimino (NNO2) neonicotinoid pharmacophore is systematically replaced by N-nitrosoimino (NNO), N-formylimino [NC(O)H], N-alkyl- and N-arylcarbonylimino [NC(O)R], and N-alkoxy- and N-aryloxycarbonylimino [NC(O)OR] variants. The NNO analogues essentially retain the binding affinity of the NNO2 compounds, while the isosteric NC(O)H congeners have diminished potency. The NC(O)R and NC(O)OR analogues, where R is methyl, trifluoromethyl, phenyl, or pyridin-3-yl, have moderate to high affinities. Orientation of the tip oxygen plays a critical role for binding of the NNO and NC(O)H pharmacophores, and the extended NC(O)R and NC(O)OR moieties are embraced by unique binding domains.

PubMedSearch : Ohno_2009_Chem.Res.Toxicol_22_476
PubMedID: 19178134

Related information

Citations formats

Ohno I, Tomizawa M, Durkin KA, Naruse Y, Casida JE, Kagabu S (2009)
Molecular features of neonicotinoid pharmacophore variants interacting with the insect nicotinic receptor
Chemical Research in Toxicology 22 :476

Ohno I, Tomizawa M, Durkin KA, Naruse Y, Casida JE, Kagabu S (2009)
Chemical Research in Toxicology 22 :476