AI Article Synopsis
- Thymidine phosphorylase (TP) is linked to several diseases like rheumatoid arthritis and cancer, making it an important target for drug development.
- A study tested twenty-five new compounds for their ability to inhibit TP, with six showing promising activity, particularly compound 5 which had an IC50 value close to the standard inhibitor.
- The most active compounds were further analyzed for their inhibition mechanisms and were found to be non-toxic to mouse fibroblast cells, suggesting potential for future therapeutic development.
Article Abstract
Thymidine phosphorylase (TP) over expression plays an important role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. In this regard, a series of twenty-five 2-arylquinazolin-4(3H)-one derivatives 1-25 were evaluated for thymidine phosphorylase inhibitory activity. Six compounds 5, 6, 20, 2, 23, and 3 were found to be active against thymidine phosphorylase enzyme with IC50 values in the range of 42.9-294.6μM. 7-Deazaxanthine (IC50=41.0±1.63μM) was used as a standard inhibitor. Compound 5 showed a significant activity (IC50=42.9±1.0μM), comparable to the standard. The enzyme kinetic studies on the most active compounds 5, 6, and 20 were performed for the determination of their modes of inhibition, and dissociation constants Ki. All active compounds were found to be largely non-cytotoxic against the mouse fibroblast 3T3 cell line. This study identifies a novel class of thymidine phosphorylase inhibitors which may be further investigated as leads to develop therapeutic agents.
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| http://dx.doi.org/10.1016/j.bioorg.2015.10.006 | DOI Listing |
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