title: Design, Synthesis and Biological Evaluation of α-Aminophosphonate Derivatives Containing a Pyrazole Moiety.
abstract: Acetylcholinesterase (AChE) is a key enzyme which present in the central nervous system of living organisms. Organophosphorus pesticides (OPs) that serve as insecticides are AChE inhibitors which have been used widely in agriculture. A series of novel OPs containing pyrazole moiety have been designed and synthesized. The biological evaluation indicated compound 4e appeared 81% larvicidal activity against Plutella xylostella at the concentration of 0.1 mg/L and the inhibition of AChE by compound 4e was distinctly enhanced with the increasing doses. Molecular docking of compound 4e into the three dimensional X-ray structure of the Drosophila melanogaster AChE (DmAChE, PDB code: 1QO9) was carried out utilizating the Discovery Studio (DS), the binding model revealed that the title structure was tightly embedded in the binding sites of DmAChE. Therefore, we suggest that compound 4e may serve as a novel AChE inhibitor that can be utilized as a new insecticidal drug.
authors.affiliation: School of Plant Protection, Anhui Agricultural University.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Ren
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Li
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Chu
authors.forename: Li-Song
authors.initials: LS
authors.lastname: Zhang
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Yao
authors.forename: Yong
authors.initials: Y
authors.lastname: Xia
authors.forename: Xian-Hai
authors.initials: XH
authors.lastname: Lv
authors.forename: Hai-Qun
authors.initials: HQ
authors.lastname: Cao
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D009036:Moths / Q000187:drug effects* / Q000201:enzymology; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D063065:Organophosphonates; D011720:Pyrazoles; C031280:pyrazole; D000110:Acetylcholinesterase