Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II
In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5] triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deaz...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
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Elsevier Masson SAS
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/34693 |
| _version_ | 1848754292895252480 |
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| author | Bera, H. Ojha, P. Tan, B. Sun, L. Dolzhenko, Anton Chui, W. Chiu, G. |
| author_facet | Bera, H. Ojha, P. Tan, B. Sun, L. Dolzhenko, Anton Chui, W. Chiu, G. |
| author_sort | Bera, H. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5] triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 µM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties. © 2014 Elsevier Masson SAS. All rights reserved. |
| first_indexed | 2025-11-14T08:38:06Z |
| format | Journal Article |
| id | curtin-20.500.11937-34693 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:38:06Z |
| publishDate | 2014 |
| publisher | Elsevier Masson SAS |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-346932017-09-13T12:22:47Z Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II Bera, H. Ojha, P. Tan, B. Sun, L. Dolzhenko, Anton Chui, W. Chiu, G. In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5] triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 µM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties. © 2014 Elsevier Masson SAS. All rights reserved. 2014 Journal Article http://hdl.handle.net/20.500.11937/34693 10.1016/j.ejmech.2014.03.063 Elsevier Masson SAS restricted |
| spellingShingle | Bera, H. Ojha, P. Tan, B. Sun, L. Dolzhenko, Anton Chui, W. Chiu, G. Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II |
| title | Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II |
| title_full | Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II |
| title_fullStr | Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II |
| title_full_unstemmed | Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II |
| title_short | Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: Synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II |
| title_sort | discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. part ii |
| url | http://hdl.handle.net/20.500.11937/34693 |