TY - JOUR
T1 - N-Alkyl-1,5-dideoxy-1,5-imino-L-fucitols as fucosidase inhibitors: 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.
N1 - Funding Information:
Research presented herein was supported by Science Foundation Ireland (07/IN.1/B966), the Irish Research Council (GOI PhD Scholarships to JZ, AN) and the European Commission through COST Action CM1106. The authors thank Guan-Nan Wang for recording NMR spectra and to Nadine Martinet for organization of the COST Action CM1106 screening library that led to identification of the activity for 16 . The authors thank Dr. Stephen Rea and Dr. Helen Dodson for gifts of tumour cells.
Publisher Copyright:
© 2018 Elsevier Inc.
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 - N-alkylation
KW - Iminosugar
KW - Fucosidase
KW - Homology modelling
KW - Anti-cancer activity
UR - http://www.scopus.com/inward/record.url?scp=85058219909&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2018.12.003
DO - 10.1016/j.bioorg.2018.12.003
M3 - Article
C2 - 30554081
AN - SCOPUS:85058219909
SN - 0045-2068
VL - 84
SP - 418
EP - 433
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
ER -
