title: Development of Unsymmetrical Dyads As Potent Noncarbohydrate-Based Inhibitors against Human β-N-Acetyl-d-hexosaminidase.
abstract: Human β-N-acetyl-d-hexosaminidase has gained much attention due to its roles in several pathological processes and been considered as potential targets for disease therapy. A novel and efficient skeleton, which was an unsymmetrical dyad containing naphthalimide and methoxyphenyl moieties with an alkylamine spacer linkage as a noncarbohydrate-based inhibitor, was synthesized, and the activities were valuated against human β-N-acetyl-d-hexosaminidase. The most potent inhibitor exhibits high inhibitory activity with K i values of 0.63 μM. The straightforward synthetic manners of these unsymmetrical dyads and understanding of the binding model could be advantageous for further structure optimization and development of new therapeutic agents for Hex-related diseases.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals, School of Pharmacy, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology , Dalian 116024, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Life Science and Biotechnology, Dalian University of Technology , Dalian 116024, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals, 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 , Dalian 116024, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals, School of Pharmacy, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
keywords: GM2 gangliosides; Naphthalimide; inhibitors; noncarbohydrates; β-N-acetyl-d-hexosaminidase