N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines

Jian Zhou; Arvind Negi; Styliana I. Mirallai; Rolf Warta; Christel Herold-Mende; Michael P. Carty; Xin-Shan Ye; Paul V. Murphy

doi:10.13025/14841

N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines

Jian Zhou
, Arvind Negi
, Styliana I. Mirallai
, Rolf Warta
, Christel Herold-Mende
, Michael P. Carty
, Xin-Shan Ye
, Paul V. Murphy

University College Dublin
University of Galway
Heidelberg University
Peking University Health Science Center

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

18 Citations (Scopus)

Abstract

1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The N-alkyl derivatives were inactive against the bacterial fucosidase, while inhibiting the bovine enzyme. Docking of inhibitors to homology models, generated for the bovine and human fucosidases, was carried out. N-Decyl-DFJ was toxic to cancer cell lines and was more potent than the other N-alkyl DFJs studied.

Original language	English
Pages (from-to)	418-433
Number of pages	16
Journal	Bioorganic Chemistry
Volume	84
DOIs	https://doi.org/10.13025/14841 https://doi.org/10.1016/j.bioorg.2018.12.003
Publication status	Published - Mar 2019

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

1-Deoxyfuconojirimycin
Anti-cancer activity
Fucosidase
Homology modelling
Iminosugar
N-alkylation

Access to Document

10.13025/14841Licence: CC BY-NC-ND
10.1016/j.bioorg.2018.12.003

Revision for SubmissionAccepted author manuscript, 1.64 MBLicence: CC BY-NC-ND

Cite this

@article{8d79d58e67e74b82ba6ae031eb64a106,

title = "N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines",

abstract = "1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The N-alkyl derivatives were inactive against the bacterial fucosidase, while inhibiting the bovine enzyme. Docking of inhibitors to homology models, generated for the bovine and human fucosidases, was carried out. N-Decyl-DFJ was toxic to cancer cell lines and was more potent than the other N-alkyl DFJs studied.",

keywords = "1-Deoxyfuconojirimycin, Anti-cancer activity, Fucosidase, Homology modelling, Iminosugar, N-alkylation",

author = "Jian Zhou and Arvind Negi and Mirallai, \{Styliana I.\} and Rolf Warta and Christel Herold-Mende and Carty, \{Michael P.\} and Xin-Shan Ye and Murphy, \{Paul V.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2019",

month = mar,

doi = "10.13025/14841",

language = "English",

volume = "84",

pages = "418--433",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors

T2 - Synthesis, molecular modelling and activity against cancer cell lines

AU - Zhou, Jian

AU - Negi, Arvind

AU - Mirallai, Styliana I.

AU - Warta, Rolf

AU - Herold-Mende, Christel

AU - Carty, Michael P.

AU - Ye, Xin-Shan

AU - Murphy, Paul V.

PY - 2019/3

Y1 - 2019/3

N2 - 1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The N-alkyl derivatives were inactive against the bacterial fucosidase, while inhibiting the bovine enzyme. Docking of inhibitors to homology models, generated for the bovine and human fucosidases, was carried out. N-Decyl-DFJ was toxic to cancer cell lines and was more potent than the other N-alkyl DFJs studied.

AB - 1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The N-alkyl derivatives were inactive against the bacterial fucosidase, while inhibiting the bovine enzyme. Docking of inhibitors to homology models, generated for the bovine and human fucosidases, was carried out. N-Decyl-DFJ was toxic to cancer cell lines and was more potent than the other N-alkyl DFJs studied.

KW - 1-Deoxyfuconojirimycin

KW - Anti-cancer activity

KW - Fucosidase

KW - Homology modelling

KW - Iminosugar

KW - N-alkylation

UR - http://hdl.handle.net/10379/16431

UR - https://www.scopus.com/pages/publications/85058219909

U2 - 10.13025/14841

DO - 10.13025/14841

M3 - Article

SN - 0045-2068

VL - 84

SP - 418

EP - 433

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

ER -

N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: Synthesis, molecular modelling and activity against cancer cell lines

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this