title: Docking model of the nicotinic acetylcholine receptor and nitromethylene neonicotinoid derivatives with a longer chiral substituent and their biological activities.
abstract: In the present study, nitromethylene neonicotinoid derivatives possessing substituents that contain a sulfur atom, oxygen atom or aromatic ring at position 5 on the imidazolidine ring were synthesized to evaluate their affinity for the nicotinic acetylcholine receptor (nAChR) and their insecticidal activity against adult female houseflies. Comparing the receptor affinity of the alkylated derivative with the receptor affinity of compounds possessing either ether or thioether groups revealed that conversion of the carbon atom to a sulfur atom did not influence the receptor affinity, whereas conversion to an oxygen atom was disadvantageous for the receptor affinity. The receptor affinity of compounds possessing a benzyl or phenyl group was lower than that of the unsubstituted compound. Analysis of the three-dimensional quantitative structure-activity relationship using comparative molecular field analysis demonstrated that steric hindrance of the receptor should exist around the C3 of an n-butyl group attached at position 5 on the imidazolidine ring. A docking study of the nAChR-ligand model suggested that the ligand-binding region expands as the length of the substituent increases by brushing against the amino acids that form the binding region. The insecticidal activity of the compounds was positively correlated with the receptor affinity by considering logP and the number of heteroatoms, including sulfur and oxygen atoms, in the substituents, suggesting that the insecticidal activity is influenced by the receptor affinity, hydrophobicity, and metabolic stability of the compounds.
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nagaoka
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan. Electronic address: nishiwaki.hisashi.mg@ehime-u.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nishiwaki
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kita-Shirakawa, Sakyo-Ku, Kyoto 606-8502, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Akamatsu
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shuto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D005260:Female; D006793:Houseflies / Q000187:drug effects* / Q000502:physiology; D007306:Insecticides / Q000737:chemistry* / Q000378:metabolism*; D008745:Methylation; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009574:Nitro Compounds / Q000737:chemistry* / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007306:Insecticides; D009574:Nitro Compounds; D011978:Receptors, Nicotinic
keywords: Docking model; Musca domestica; Nicotinic acetylcholine receptor; Nitromethylene neonicotinoids; QSAR