title: Novel and selective acetylcholinesterase inhibitors for Tetranychus cinnabarinus (Acari: Tetranychidae).
abstract: The carmine spider mite, Tetranychus cinnabarinus (Acari: Tetranychidae), is an economically important and extremely polyphagous herbivorous pest, with the title of "resistance champion" among arthropods. Anticholinesterase insecticides such as organophosphate and carbamate account for more than one-third of global insecticide sales. The non-target toxicity and resistance problem of organophosphate and carbamate have become of growing concern, which may be due to the fact that they target the ubiquitous catalytic serine residue of acetylcholinesterase (AChE) in mammals, birds, and beneficial insects. In this study, the structural differences between T. cinnabarinus AChE and human AChE, at or near the catalytic pocket, were illustrated. From the SPECS chemical lead-compound database, 55 AChE inhibitor candidates were screened for high affinity for T. cinnabarinus AChE, but low affinity for human AChE, using the DOCK 6 and AutoDock Vina software. Three of the fifty-five candidates had inhibitory activity greater than that of the reversible AChE inhibitor eserine, with no observed inhibitory activities against human AChE. Two of the three had toxicity to T. cinnabarinus comparable to that of natural insecticidal pyrethrins. However, their potency is low compared with that of etoxazole, and further work is needed to optimize their potency. The selectivity of the three compounds over human and mite AChE may be due to their interaction with the mite-specific residues, as analyzed by Cyscore. The three compounds are potential lead compounds for development of novel acaricides against T. cinnabarinus with reduced toxicity to non-target species and a low propensity for resistance.
authors.affiliation: College of Biological Science and Engineering, Beijing University of Agriculture, Beijing 102206, China; Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture People's Republic of China, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Chunya
authors.initials: C
authors.lastname: Bu
authors.affiliation: Plant Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Center for Growth, Metabolism and Aging, Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Biological Science and Engineering, Beijing University of Agriculture, Beijing 102206, China; Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture People's Republic of China, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Biological Science and Engineering, Beijing University of Agriculture, Beijing 102206, China; Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture People's Republic of China, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Plant Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Biological Science and Engineering, Beijing University of Agriculture, Beijing 102206, China; Key Laboratory of Urban Agriculture (North) of Ministry of Agriculture People's Republic of China, Beijing University of Agriculture, Beijing 102206, China. Electronic address: 20107702@bua.edu.cn.
authors.forename: Guanglu
authors.initials: G
authors.lastname: Shi
mesh_terms: D056810:Acaricides / Q000737:chemistry*; D000110:Acetylcholinesterase / Q000737:chemistry*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D006801:Humans; D007305:Insecticide Resistance; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D040102:Tetranychidae / Q000201:enzymology*
chemical_list: D056810:Acaricides; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase
keywords: Anticholinesterase; Human; Selective insecticides; Tetranychus cinnabarinus