Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.ejmech.2013.03.063
DC Field | Value | |
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dc.title | Synthesis of pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors of thymidine phosphorylase | |
dc.contributor.author | Sun, L. | |
dc.contributor.author | Bera, H. | |
dc.contributor.author | Chui, W.K. | |
dc.date.accessioned | 2014-10-29T01:59:33Z | |
dc.date.available | 2014-10-29T01:59:33Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Sun, L., Bera, H., Chui, W.K. (2013). Synthesis of pyrazolo[1,5-a][1,3,5]triazine derivatives as inhibitors of thymidine phosphorylase. European Journal of Medicinal Chemistry 65 : 1-11. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejmech.2013.03.063 | |
dc.identifier.issn | 02235234 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/106406 | |
dc.description.abstract | Thymidine phosphorylase (TP) is an enzyme that promotes tumor growth and metastasis and therefore is an attractive druggable target. Using a reported TP inhibitor, 7-deazaxanthine (7DX), as the lead compound; this study was set up to evaluate whether pyrazolo[1,5-a][1,3,5]triazin-2,4-diones and pyrazolo[ 1,5- a][1,3,5]triazin-2-thioxo-4-ones would exhibit TP inhibitory activity. The pyrazolo[1,5-a][1,3,5] triazine nucleus was constructed using a reaction that annulated the 1,3,5-triazine ring onto a pyrazole scaffold. Among the 52 compounds synthesized and tested, it was found that 1,3-dihydro-pyrazolo[1,5-a] [1,3,5]triazin-2-thioxo-4-ones exhibited various extent of inhibitory activity against TP. The best compound 17p, which bears a para-substituted pentafluorosulfur group, showed an IC50 value of 0.04 μM, which was around 800 times more potent than the 7DX (IC50 = 32 μM) under the same bioassay conditions. The results of the study suggested that a substituent with +σ and +π properties inserted at position 4 of a phenyl ring that is attached to position 8 of the pyrazolo[1,5-a][1,3,5]triazin- 2-thioxo-4-one scaffold would give excellent TP inhibitory action. In addition, 17p was found to be a non-competitive inhibitor thus suggested that it might interact with TP at a position different from the substrate binding site. © 2013 Elsevier Masson SAS. All rights reserved. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.ejmech.2013.03.063 | |
dc.source | Scopus | |
dc.subject | Enzyme inhibitor | |
dc.subject | Pyrazolo[1,5-a][1,3,5]triazines | |
dc.subject | Thymidine phosphorylase | |
dc.type | Article | |
dc.contributor.department | PHARMACY | |
dc.description.doi | 10.1016/j.ejmech.2013.03.063 | |
dc.description.sourcetitle | European Journal of Medicinal Chemistry | |
dc.description.volume | 65 | |
dc.description.page | 1-11 | |
dc.description.coden | EJMCA | |
dc.identifier.isiut | 000322850100001 | |
Appears in Collections: | Staff Publications |
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