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Thioureido N-acetyllactosamine derivatives as potent galectin-7 and 9N inhibitors

Salameh, Bader LU ; Sundin, Anders LU ; Leffler, Hakon LU and Nilsson, Ulf LU (2006) In Bioorganic & Medicinal Chemistry 14(4). p.1215-1220
Abstract
Derivatives of N-acetyllactosamine carrying structurally diverse thioureido groups at galactose C3 were prepared from a C3'-azido N-acetyllactosamine derivative in a three-step reaction sequence involving azide reduction and isothiocyanate formation by thiophosgene treatment of the C3-amine, followed by reaction of the isothiocyanate with a panel of amines. Evaluation of the N-acetyllactosamine thioureas as inhibitors against galectins-1, 3, 7, 8N (N-terminal domain), and 9N (N-terminal domain) revealed thiourea-mediated affinity enhancements for galectins-1, 3, 7, and 9N. In particular, good inhibitors were discovered against galectin-7 and 9N (K-d 23 and 47 mu M, respectively, for a 3-pyridylinethylthiourea derivative), which represents... (More)
Derivatives of N-acetyllactosamine carrying structurally diverse thioureido groups at galactose C3 were prepared from a C3'-azido N-acetyllactosamine derivative in a three-step reaction sequence involving azide reduction and isothiocyanate formation by thiophosgene treatment of the C3-amine, followed by reaction of the isothiocyanate with a panel of amines. Evaluation of the N-acetyllactosamine thioureas as inhibitors against galectins-1, 3, 7, 8N (N-terminal domain), and 9N (N-terminal domain) revealed thiourea-mediated affinity enhancements for galectins-1, 3, 7, and 9N. In particular, good inhibitors were discovered against galectin-7 and 9N (K-d 23 and 47 mu M, respectively, for a 3-pyridylinethylthiourea derivative), which represents more than an order of magnitude affinity enhancement over the parent natural N-acetyllactosamine. (c) 2005 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
N-acetyllactosamine, thiourea, galectin, inhibitor
in
Bioorganic & Medicinal Chemistry
volume
14
issue
4
pages
1215 - 1220
publisher
Elsevier
external identifiers
  • wos:000234909700036
  • pmid:16242339
  • scopus:30344486680
ISSN
0968-0896
DOI
10.1016/j.bmc.2005.09.050
language
English
LU publication?
yes
id
ea4cabf8-25a8-4564-a55f-f64eb236e67f (old id 419553)
date added to LUP
2007-10-17 18:18:34
date last changed
2019-01-06 06:09:16
@article{ea4cabf8-25a8-4564-a55f-f64eb236e67f,
  abstract     = {Derivatives of N-acetyllactosamine carrying structurally diverse thioureido groups at galactose C3 were prepared from a C3'-azido N-acetyllactosamine derivative in a three-step reaction sequence involving azide reduction and isothiocyanate formation by thiophosgene treatment of the C3-amine, followed by reaction of the isothiocyanate with a panel of amines. Evaluation of the N-acetyllactosamine thioureas as inhibitors against galectins-1, 3, 7, 8N (N-terminal domain), and 9N (N-terminal domain) revealed thiourea-mediated affinity enhancements for galectins-1, 3, 7, and 9N. In particular, good inhibitors were discovered against galectin-7 and 9N (K-d 23 and 47 mu M, respectively, for a 3-pyridylinethylthiourea derivative), which represents more than an order of magnitude affinity enhancement over the parent natural N-acetyllactosamine. (c) 2005 Elsevier Ltd. All rights reserved.},
  author       = {Salameh, Bader and Sundin, Anders and Leffler, Hakon and Nilsson, Ulf},
  issn         = {0968-0896},
  keyword      = {N-acetyllactosamine,thiourea,galectin,inhibitor},
  language     = {eng},
  number       = {4},
  pages        = {1215--1220},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry},
  title        = {Thioureido N-acetyllactosamine derivatives as potent galectin-7 and 9N inhibitors},
  url          = {http://dx.doi.org/10.1016/j.bmc.2005.09.050},
  volume       = {14},
  year         = {2006},
}