title: Synthesis, insecticidal activity, crystal structure, and molecular docking studies of nitenpyram analogues with an ω-hydroxyalkyl ester arm anchored on the tetrahydropyrimidine ring.
abstract: On the basis of the research of the proposed modes of action between neonicotinoids and insect nicotinic acetylcholine receptor (nAChR), a new series of nitenpyram analogues with an ω-hydroxyalkyl ester arm anchored on the tetrahydropyrimidine ring was designed and synthesized to further enhance the strength of the hydrogen-bonding action they display in binding with the nAChR. The structures of the target compounds were characterized by (1)H NMR, IR, and elemental analysis, and the cis configuration was confirmed by X-ray diffraction. Preliminary bioassays indicated that all of the nitenpyram analogues exhibited good insecticidal activity against Nilaparvata lugens and Myzus persicae at 100 mg/L, whereas analogues 4d and 6a afforded the best in vitro activity that had ≥ 95% mortality at 4 mg/L; the LC(50) values of the analogues 4d and 6a were 0.170 and 0.154 mg/L, respectively. Structure-activity relationship (SAR) studies suggested that their insecticidal potency was also dual-controlled by the flexibility and size of the molecule. In addition, molecular docking simulations revealed that analogues 4d and 6a displayed stronger hydrogen-bonding action in binding with the nAChR, which explained the SARs observed in vitro and implied that the designed nitenpyram analogues are both practical and feasible.
authors.affiliation: College of Life and Environment Sciences, Shanghai Normal University , Shanghai 200234, China. willin112@163.com
authors.forename: Chuan-Wen
authors.initials: CW
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Fang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Zhi-bing
authors.initials: ZB
authors.lastname: Hao
authors.forename: Shi-bing
authors.initials: SB
authors.lastname: Nan
mesh_terms: D000818:Animals; D001042:Aphids / Q000187:drug effects; D018360:Crystallography, X-Ray; D004952:Esters; D006430:Hemiptera / Q000187:drug effects; D006860:Hydrogen Bonding; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D000073943:Neonicotinoids; D011725:Pyridines / Q000737:chemistry*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D004952:Esters; D007306:Insecticides; D000073943:Neonicotinoids; D011725:Pyridines; D011978:Receptors, Nicotinic; C464843:nitenpyram