Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors
In our lead finding program, a series of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positi...
| Main Authors: | , , , , |
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| Format: | Journal Article |
| Published: |
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/33573 |
| _version_ | 1848753984388464640 |
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| author | Bera, H. Dolzhenko, Anton Sun, L. Dutta Gupta, S. Chui, W. |
| author_facet | Bera, H. Dolzhenko, Anton Sun, L. Dutta Gupta, S. Chui, W. |
| author_sort | Bera, H. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | In our lead finding program, a series of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positions showed varying degrees of TP inhibitory activity comparable with positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 µm). Enzyme inhibition kinetics study suggested that compound IVn behaved as a mixed-type inhibitor of the enzyme with respect to thymidine (dThd) as a variable substrate. Compound IVn was also found to inhibit PMA-induced MMP-9 expression in MDA-MB-231 cells at sublethal concentrations. Computational docking study was performed to illustrate the enzyme inhibition kinetics and to explore the ligand-enzyme interactions. © 2013 John Wiley & Sons A/S. |
| first_indexed | 2025-11-14T08:33:12Z |
| format | Journal Article |
| id | curtin-20.500.11937-33573 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:33:12Z |
| publishDate | 2013 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-335732017-09-13T12:23:29Z Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors Bera, H. Dolzhenko, Anton Sun, L. Dutta Gupta, S. Chui, W. In our lead finding program, a series of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives were synthesized, and their in vitro thymidine phosphorylase inhibitory potential was explored. Among the different derivatives, compounds having keto group (C = O) at C7 and thioketo group (C = S) at C5 positions showed varying degrees of TP inhibitory activity comparable with positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 µm). Enzyme inhibition kinetics study suggested that compound IVn behaved as a mixed-type inhibitor of the enzyme with respect to thymidine (dThd) as a variable substrate. Compound IVn was also found to inhibit PMA-induced MMP-9 expression in MDA-MB-231 cells at sublethal concentrations. Computational docking study was performed to illustrate the enzyme inhibition kinetics and to explore the ligand-enzyme interactions. © 2013 John Wiley & Sons A/S. 2013 Journal Article http://hdl.handle.net/20.500.11937/33573 10.1111/cbdd.12171 restricted |
| spellingShingle | Bera, H. Dolzhenko, Anton Sun, L. Dutta Gupta, S. Chui, W. Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| title | Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| title_full | Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| title_fullStr | Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| title_full_unstemmed | Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| title_short | Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| title_sort | synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors |
| url | http://hdl.handle.net/20.500.11937/33573 |