Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase
Language English Country Great Britain, England Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
20053558
DOI
10.1016/j.bmcl.2009.12.081
PII: S0960-894X(09)01804-6
Knihovny.cz E-resources
- MeSH
- Inhibitory Concentration 50 MeSH
- Rats MeSH
- Humans MeSH
- Lymphoma, T-Cell enzymology MeSH
- Nucleosides chemistry pharmacology MeSH
- Organophosphonates chemistry pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Thymidine Phosphorylase antagonists & inhibitors metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Nucleosides MeSH
- Organophosphonates MeSH
- Thymidine Phosphorylase MeSH
Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic acids were evaluated for their ability to inhibit thymidine phosphorylase (TP, EC 2.4.2.4) purified from spontaneous T-cell lymphomas of an inbred Sprague-Dawley rat strain. From a large set of tested compounds, among them a number of pyrrolidine-based derivatives, 10 nucleotide analogues with IC(50) values below 1 microM were selected. Out of them, four compounds strongly inhibited the enzyme with IC(50) values lying in a range of 11-45 nM. These most potent compounds might be bi-substrate analogues.
References provided by Crossref.org
Pyrrolidine nucleotide analogs with a tunable conformation
