Advanced

1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors

Salameh, Bader A.; Cumpstey, Ian LU ; Sundin, Anders LU ; Leffler, Hakon LU and Nilsson, Ulf LU (2010) In Bioorganic & Medicinal Chemistry 18(14). p.5367-5378
Abstract
Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010... (More)
Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Galactose, Inhibition, Triazole, Galectin, Azide
in
Bioorganic & Medicinal Chemistry
volume
18
issue
14
pages
5367 - 5378
publisher
Elsevier
external identifiers
  • wos:000279744700056
  • scopus:77955335001
ISSN
0968-0896
DOI
10.1016/j.bmc.2010.05.040
language
English
LU publication?
yes
id
2c9f5382-d477-432d-8ce3-0ca3cde1acfc (old id 1657693)
date added to LUP
2010-08-24 11:20:30
date last changed
2018-06-10 03:06:20
@article{2c9f5382-d477-432d-8ce3-0ca3cde1acfc,
  abstract     = {Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved.},
  author       = {Salameh, Bader A. and Cumpstey, Ian and Sundin, Anders and Leffler, Hakon and Nilsson, Ulf},
  issn         = {0968-0896},
  keyword      = {Galactose,Inhibition,Triazole,Galectin,Azide},
  language     = {eng},
  number       = {14},
  pages        = {5367--5378},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry},
  title        = {1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors},
  url          = {http://dx.doi.org/10.1016/j.bmc.2010.05.040},
  volume       = {18},
  year         = {2010},
}