Design and synthesis of iso-allo-DNJ and L-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase

Lin-Feng Yang; Ming Zhang; Yuna Shimadate; Atsushi Kato; Tian-Yang Liu Hou; Yi-Xian Li; Yue-Mei Jia; George W J Fleet; Chu-Yi Yu

doi:10.1039/d3ob00404j

Design and synthesis of iso-allo-DNJ and L-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase

Lin-Feng Yang, Ming Zhang, Yuna Shimadate, Atsushi Kato, Tian-Yang Liu Hou, Yi-Xian Li, Yue-Mei Jia, George W J Fleet, Chu-Yi Yu

University of Toyama

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

1 Scopus citations

Abstract

A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC50 = 9.3 μM) than the others. Molecular docking study revealed different docking modes of the iso-allo-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.

Original language	English
Pages (from-to)	3453-3464
Number of pages	12
Journal	Organic and Biomolecular Chemistry
Volume	21
Issue number	16
DOIs	https://doi.org/10.1039/d3ob00404j
State	Published - 2023/04/26

Keywords

alpha-Glucosidases/metabolism
Structure-Activity Relationship
Molecular Docking Simulation
Glycoside Hydrolase Inhibitors/pharmacology
Glycoside Hydrolases
Molecular Structure

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10.1039/d3ob00404j

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title = "Design and synthesis of iso-allo-DNJ and L-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase",

abstract = "A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC50 = 9.3 μM) than the others. Molecular docking study revealed different docking modes of the iso-allo-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.",

keywords = "alpha-Glucosidases/metabolism, Structure-Activity Relationship, Molecular Docking Simulation, Glycoside Hydrolase Inhibitors/pharmacology, Glycoside Hydrolases, Molecular Structure",

author = "Lin-Feng Yang and Ming Zhang and Yuna Shimadate and Atsushi Kato and Hou, {Tian-Yang Liu} and Yi-Xian Li and Yue-Mei Jia and Fleet, {George W J} and Chu-Yi Yu",

year = "2023",

month = apr,

day = "26",

doi = "10.1039/d3ob00404j",

language = "英語",

volume = "21",

pages = "3453--3464",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Design and synthesis of iso-allo-DNJ and L-isoDALDP derivatives

T2 - pursuit of potent and selective inhibitors of α-glucosidase

AU - Yang, Lin-Feng

AU - Zhang, Ming

AU - Shimadate, Yuna

AU - Kato, Atsushi

AU - Hou, Tian-Yang Liu

AU - Li, Yi-Xian

AU - Jia, Yue-Mei

AU - Fleet, George W J

AU - Yu, Chu-Yi

PY - 2023/4/26

Y1 - 2023/4/26

N2 - A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC50 = 9.3 μM) than the others. Molecular docking study revealed different docking modes of the iso-allo-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.

AB - A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC50 = 9.3 μM) than the others. Molecular docking study revealed different docking modes of the iso-allo-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.

KW - alpha-Glucosidases/metabolism

KW - Structure-Activity Relationship

KW - Molecular Docking Simulation

KW - Glycoside Hydrolase Inhibitors/pharmacology

KW - Glycoside Hydrolases

KW - Molecular Structure

U2 - 10.1039/d3ob00404j

DO - 10.1039/d3ob00404j

M3 - 学術論文

C2 - 37039337

SN - 1477-0520

VL - 21

SP - 3453

EP - 3464

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 16

ER -

Design and synthesis of iso-allo-DNJ and L-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase

Abstract

Keywords

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