Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones
In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacologi...
| Main Authors: | , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
2013
|
| Online Access: | http://hdl.handle.net/20.500.11937/24261 |
| _version_ | 1848751379309395968 |
|---|---|
| author | Bera, H. Lee, M. Sun, L. Dolzhenko, Anton Chui, W. |
| author_facet | Bera, H. Lee, M. Sun, L. Dolzhenko, Anton Chui, W. |
| author_sort | Bera, H. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 lM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions. © 2013 Elsevier Inc. All rights reserved. |
| first_indexed | 2025-11-14T07:51:47Z |
| format | Journal Article |
| id | curtin-20.500.11937-24261 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:51:47Z |
| publishDate | 2013 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-242612017-09-13T12:22:46Z Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones Bera, H. Lee, M. Sun, L. Dolzhenko, Anton Chui, W. In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1, 3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 lM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leading to a reduced inhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions. © 2013 Elsevier Inc. All rights reserved. 2013 Journal Article http://hdl.handle.net/20.500.11937/24261 10.1016/j.bioorg.2013.07.004 restricted |
| spellingShingle | Bera, H. Lee, M. Sun, L. Dolzhenko, Anton Chui, W. Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| title | Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| title_full | Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| title_fullStr | Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| title_full_unstemmed | Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| title_short | Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| title_sort | synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones |
| url | http://hdl.handle.net/20.500.11937/24261 |