Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 34 - 40 |
| Number of pages | 7 |
| Journal | Bioorganic Chemistry |
| Volume | 50 |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
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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, Hriday; Lee, Min Huey; Sun, Lingyi; Dolzhenko, Anton V; Chui, Wai-Keung.
In: Bioorganic Chemistry, Vol. 50, 2013, p. 34 - 40.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones
AU - Bera, Hriday
AU - Lee, Min Huey
AU - Sun, Lingyi
AU - Dolzhenko, Anton V
AU - Chui, Wai-Keung
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.sciencedirect.com/science/article/pii/S0045206813000461?via=ihub
U2 - 10.1016/j.bioorg.2013.07.004
DO - 10.1016/j.bioorg.2013.07.004
M3 - Article
VL - 50
SP - 34
EP - 40
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
SN - 0045-2068
ER -