Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejmech.2014.03.063
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
Authors: Bera, H.
Ojha, P.K.
Tan, B.J.
Sun, L.
Dolzhenko, A.V. 
Chui, W.-K. 
Chiu, G.N.C. 
Keywords: Antiangiogenesis
Breast cancer
Mixed-type inhibition
Pyrazolo[1,5-a][1,3,5]triazine
Thymidine phosphorylase inhibitors
Issue Date: 6-May-2014
Citation: Bera, H., Ojha, P.K., Tan, B.J., Sun, L., Dolzhenko, A.V., Chui, W.-K., Chiu, G.N.C. (2014-05-06). 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. European Journal of Medicinal Chemistry 78 : 294-303. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejmech.2014.03.063
Abstract: 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.
Source Title: European Journal of Medicinal Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/105840
ISSN: 17683254
DOI: 10.1016/j.ejmech.2014.03.063
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

18
checked on May 17, 2018

WEB OF SCIENCETM
Citations

16
checked on May 9, 2018

Page view(s)

60
checked on May 18, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.