Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 70, Issue -, Pages 685-691Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2013.10.053
Keywords
Adenosine; Ecto-5 '-nucleotidase; Enzyme inhibition; Sulfonic acids; Binding mode; Cytotoxicity
Categories
Funding
- German-Pakistani Research Collaboration Program
- Canadian Institutes of Health Research (CIHR)
- Fonds de Recherche du Quebec - Sante (FRQS)
- Jurgen Manchot Foundation, Dusseldorf, Germany
Ask authors/readers for more resources
Ecto-5'-nucleotidase (CD73) is well known for its implication in cancer. Inhibition of ecto-5'-nucleotidases is thought to provide an attractive approach to cancer therapy. This study identifies sulfonic acid compounds as efficient inhibitors of ecto-5'-nucleotidases. The compounds were tested against recombinant human and rat ecto-5'-nucleotidases. The most potent new sulfonic acid inhibitor 6-amino-4-hydroxynaphthalene-2-sulfonic acid (1) of ecto-5'-nucleotidase had an IC50 of 1.32 +/- 0.09 mu M for the human and 10.4 +/- 3.3 mu M for the rat enzyme. Generally, all compounds were more active against the human enzyme. Plausible binding mode models were developed for this new class of inhibitors. Furthermore, several sulfonic acid inhibitors were efficient cytotoxic agents when tested on H157 cancer cell lines. Hence, new ecto-5'-nucleotidases inhibitors displayed significant potential for further development as compounds for anti-cancer therapy. (C) 2013 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available