Development of unsymmetrical dyads as potent noncarbohydrate-based inhibitors against human β-N-acetyl-D-hexosaminidase

Peng Guo; Qi Chen; Tian Liu; Lin Xu; Qing Yang; Xuhong Qian

doi:10.1021/ml300475m

Development of unsymmetrical dyads as potent noncarbohydrate-based inhibitors against human β-N-acetyl-D-hexosaminidase

Peng Guo
, Qi Chen
, Tian Liu
, Lin Xu
, Qing Yang^*
, Xuhong Qian

^*Corresponding author for this work

East China University of Science and Technology
Dalian University of Technology

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English
Pages (from-to)	527-531
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	6
DOIs	https://doi.org/10.1021/ml300475m
State	Published - 13 Jun 2013
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

GM2 gangliosides
Inhibitors
Naphthalimide
Noncarbohydrates
β-N-acetyl-D-hexosaminidase

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10.1021/ml300475m

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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 Ki 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.",

keywords = "GM2 gangliosides, Inhibitors, Naphthalimide, Noncarbohydrates, β-N-acetyl-D-hexosaminidase",

author = "Peng Guo and Qi Chen and Tian Liu and Lin Xu and Qing Yang and Xuhong Qian",

year = "2013",

month = jun,

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doi = "10.1021/ml300475m",

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}

TY - JOUR

T1 - Development of unsymmetrical dyads as potent noncarbohydrate-based inhibitors against human β-N-acetyl-D-hexosaminidase

AU - Guo, Peng

AU - Chen, Qi

AU - Liu, Tian

AU - Xu, Lin

AU - Yang, Qing

AU - Qian, Xuhong

PY - 2013/6/13

Y1 - 2013/6/13

N2 - 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 Ki 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.

AB - 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 Ki 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.

KW - GM2 gangliosides

KW - Inhibitors

KW - Naphthalimide

KW - Noncarbohydrates

KW - β-N-acetyl-D-hexosaminidase

UR - https://www.scopus.com/pages/publications/84879078955

U2 - 10.1021/ml300475m

DO - 10.1021/ml300475m

M3 - 文章

AN - SCOPUS:84879078955

SN - 1948-5875

VL - 4

SP - 527

EP - 531

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 6

ER -

Development of unsymmetrical dyads as potent noncarbohydrate-based inhibitors against human β-N-acetyl-D-hexosaminidase

Abstract

UN SDGs

Keywords

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