title: Exploring unsymmetrical dyads as efficient inhibitors against the insect β-N-acetyl-D-hexosaminidase OfHex2.
abstract: The GH20 β-N-acetyl-d-hexosaminidase OfHex2 from the insect Ostrinia furnacalis (Guenée) is a target potential for eco-friendly pesticide development. Although carbohydrate-based inhibitors against β-N-acetyl-D-hexosaminidases are widely studied, highly efficient, non-carbohydrate inhibitors are more attractive due to low cost and readily synthetic manner. Based on molecular modeling analysis of the catalytic domain of OfHex2, a series of novel naphthalimide-scaffold conjugated with a small aromatic moiety by an alkylamine spacer linker were designed and evaluated as efficiently competitive inhibitors against OfHex2. The most potent one containing naphthalimide and phenyl groups spanning by an N-alkylamine linker has a Ki value of 0.37 μM, which is 6 fold lower than that of M-31850, the most potent non-carbohydrate inhibitor ever reported. The straightforward synthetic manners as well as the presumed binding model in this paper could be advantageous for further structural optimization for developing inhibitors against GH20 β-N-acetyl-D-hexosaminidases.
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, No.2 Linggong Road, Dalian, Liaoning 116024, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, No.2 Linggong Road, Dalian, Liaoning 116024, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: xhqian@ecust.edu.cn.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology, No.2 Linggong Road, Dalian, Liaoning 116024, China. Electronic address: qingyang@dlut.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D007300:Insect Control; D019476:Insect Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D007915:Lepidoptera / Q000201:enzymology*; D062105:Molecular Docking Simulation; D053644:Naphthalimides / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D019476:Insect Proteins; D007306:Insecticides; D053644:Naphthalimides; D001619:beta-N-Acetylhexosaminidases
keywords: Enzyme inhibitors; Molecular docking; Naphthalimide; Tryptophan fluorescence titration; β-N-Acetyl-d-hexosaminidase