A structure–activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities
| Autor: | Lingyi Sun, Wai Keung Chui, Gigi N.C. Chiu, Bee Jen Tan, Anton V. Dolzhenko, Hriday Bera |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Stereochemistry
Angiogenesis Angiogenesis Inhibitors Ring (chemistry) Inhibitory postsynaptic potential Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Biomarkers Tumor Humans Structure–activity relationship Enzyme Inhibitors Thymidine phosphorylase IC50 Triazine Pharmacology Thymidine Phosphorylase Dose-Response Relationship Drug Molecular Structure Triazines Vascular Endothelial Growth Factors Organic Chemistry General Medicine Triazoles Kinetics Matrix Metalloproteinase 9 chemistry Biochemistry Thymidine |
| Zdroj: | European Journal of Medicinal Chemistry. 67:325-334 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2013.06.051 |
| Popis: | Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the 5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying degree of inhibitory activity towards thymidine phosphorylase, comparable or better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 μM). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory mechanism in the presence of variable concentrations of thymidine (dThd). In addition, selected compounds were found to have a noticeable inhibitory effect on the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231 breast cancer cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect