Abstract |
Aromatic 3,3'-diesters of thiodigalactoside were synthesized in a rapid three-step sequence from commercially available thiodigalactoside and evaluated as inhibitors of cancer- and immunity-related galectins. For each of galectins-1, -3, -7, and -9N-terminal domain, aromatic 3,3'-diesters of thiodigalactoside were found to have affinities in the low micromolar range, which represents a 7-70 fold enhancement over thiodigalactoside itself. No significant improvement was found for galectin-8 N-terminal domain. Two of the compounds were selected for testing in cell culture and were shown to have potent antimigratory effects on human PC-3 prostate and human A549 nonsmall-cell lung cancer cells.
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Authors | Tamara Delaine, Ian Cumpstey, Laurent Ingrassia, Marie Le Mercier, Paul Okechukwu, Hakon Leffler, Robert Kiss, Ulf J Nilsson |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 51
Issue 24
Pg. 8109-14
(Dec 25 2008)
ISSN: 1520-4804 [Electronic] United States |
PMID | 19053747
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Esters
- Galectins
- Thiogalactosides
- thiodigalactoside
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Topics |
- Cell Line, Tumor
- Cell Movement
- Drug Design
- Drug Screening Assays, Antitumor
- Esters
- Galectins
(chemistry)
- Humans
- Inhibitory Concentration 50
- Kinetics
- Lung Neoplasms
(therapy)
- Male
- Models, Chemical
- Prostatic Neoplasms
(therapy)
- Protein Structure, Tertiary
- Thiogalactosides
(chemistry, metabolism)
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