基于喹喔啉酮结构的醛糖还原酶抑制剂的设计合成与构效关系研究

Bing Ma; Zhenya Fan; Xing Wang; Chenying Li; Changjin Zhu

doi:10.15918/j.tbit1001-0645.2020.006

基于喹喔啉酮结构的醛糖还原酶抑制剂的设计合成与构效关系研究

Translated title of the contribution: Design, Synthesis and Structure-Activity Relationship Study of Aldose Reductase Inhibitors Based on Quinoxalinone Structure

Bing Ma, Zhenya Fan^*, Xing Wang, Chenying Li, Changjin Zhu

^*Corresponding author for this work

School of Chemistry and Chemical Engineering

Beijing Institute of Technology

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

Abstract

A series of aldose reductase(ALR2) inhibitor candidates were designed and synthesized based on quinoxalin-2(1H)-one, and a carboxyl group was introduced at N1 position. Moreover, the side chain at C3 position was modified. All compounds were tested for ALR2 inhibitory activity, showing significant inhibition. The results also show that, among them, 2-(3-(4-hydroxyphenylpropenyl)-2-oxoquinoxaline-1(2H) -alkyl) acetic acid(4d) demonstrate the most potent inhibitory activity with an IC₅₀ value of 93 nmol/L, being equal to epalrestat(IC₅₀=83 nmol/L), which is the only commercial aldose reductase inhibitor(ARI). In addition, molecular docking experiments reveal that compound 4d can bind tightly to the active site of aldose reductase.

Translated title of the contribution	Design, Synthesis and Structure-Activity Relationship Study of Aldose Reductase Inhibitors Based on Quinoxalinone Structure
Original language	Chinese (Traditional)
Pages (from-to)	445-450
Number of pages	6
Journal	Beijing Ligong Daxue Xuebao/Transaction of Beijing Institute of Technology
Volume	41
Issue number	4
DOIs	https://doi.org/10.15918/j.tbit1001-0645.2020.006
Publication status	Published - Apr 2021

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title = "基于喹喔啉酮结构的醛糖还原酶抑制剂的设计合成与构效关系研究",

abstract = "A series of aldose reductase(ALR2) inhibitor candidates were designed and synthesized based on quinoxalin-2(1H)-one, and a carboxyl group was introduced at N1 position. Moreover, the side chain at C3 position was modified. All compounds were tested for ALR2 inhibitory activity, showing significant inhibition. The results also show that, among them, 2-(3-(4-hydroxyphenylpropenyl)-2-oxoquinoxaline-1(2H) -alkyl) acetic acid(4d) demonstrate the most potent inhibitory activity with an IC50 value of 93 nmol/L, being equal to epalrestat(IC50=83 nmol/L), which is the only commercial aldose reductase inhibitor(ARI). In addition, molecular docking experiments reveal that compound 4d can bind tightly to the active site of aldose reductase.",

keywords = "Aldose reductase inhibitors, Inhibitory activity, Molecular docking, Quinoxalinone",

author = "Bing Ma and Zhenya Fan and Xing Wang and Chenying Li and Changjin Zhu",

year = "2021",

month = apr,

doi = "10.15918/j.tbit1001-0645.2020.006",

language = "繁体中文",

volume = "41",

pages = "445--450",

journal = "Beijing Ligong Daxue Xuebao/Transaction of Beijing Institute of Technology",

issn = "1001-0645",

publisher = "Beijing Institute of Technology",

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T1 - 基于喹喔啉酮结构的醛糖还原酶抑制剂的设计合成与构效关系研究

AU - Ma, Bing

AU - Fan, Zhenya

AU - Wang, Xing

AU - Li, Chenying

AU - Zhu, Changjin

PY - 2021/4

Y1 - 2021/4

N2 - A series of aldose reductase(ALR2) inhibitor candidates were designed and synthesized based on quinoxalin-2(1H)-one, and a carboxyl group was introduced at N1 position. Moreover, the side chain at C3 position was modified. All compounds were tested for ALR2 inhibitory activity, showing significant inhibition. The results also show that, among them, 2-(3-(4-hydroxyphenylpropenyl)-2-oxoquinoxaline-1(2H) -alkyl) acetic acid(4d) demonstrate the most potent inhibitory activity with an IC50 value of 93 nmol/L, being equal to epalrestat(IC50=83 nmol/L), which is the only commercial aldose reductase inhibitor(ARI). In addition, molecular docking experiments reveal that compound 4d can bind tightly to the active site of aldose reductase.

AB - A series of aldose reductase(ALR2) inhibitor candidates were designed and synthesized based on quinoxalin-2(1H)-one, and a carboxyl group was introduced at N1 position. Moreover, the side chain at C3 position was modified. All compounds were tested for ALR2 inhibitory activity, showing significant inhibition. The results also show that, among them, 2-(3-(4-hydroxyphenylpropenyl)-2-oxoquinoxaline-1(2H) -alkyl) acetic acid(4d) demonstrate the most potent inhibitory activity with an IC50 value of 93 nmol/L, being equal to epalrestat(IC50=83 nmol/L), which is the only commercial aldose reductase inhibitor(ARI). In addition, molecular docking experiments reveal that compound 4d can bind tightly to the active site of aldose reductase.

KW - Aldose reductase inhibitors

KW - Inhibitory activity

KW - Molecular docking

KW - Quinoxalinone

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U2 - 10.15918/j.tbit1001-0645.2020.006

DO - 10.15918/j.tbit1001-0645.2020.006

M3 - 文章

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SN - 1001-0645

VL - 41

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EP - 450

JO - Beijing Ligong Daxue Xuebao/Transaction of Beijing Institute of Technology

JF - Beijing Ligong Daxue Xuebao/Transaction of Beijing Institute of Technology

IS - 4

ER -

基于喹喔啉酮结构的醛糖还原酶抑制剂的设计合成与构效关系研究

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