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
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Baxter, Fiona O. (2001)This thesis reports structure-function assessments made using site-directed mutagenesis of the human enzyme 5alpha-reductase (5AR), an enzyme crucial for normal masculine development. These assessments utilised the ...
Yong, A.; Obanijesu, Emmanuel (2015)Monoethylene glycol (MEG), a common hydrate inhibitor in natural gas transportation pipelines is usually regenerated and reused to minimize operating costs. In this study, three corrosion inhibitors and a scale inhibitor ...
Tan, Yong-jun (1996)This thesis mainly concerns the application of electrochemical impedance spectroscopy (EIS) and electrochemical noise analysis (ENA) to the study of CO(subscript)2 corrosion of mild steel and its inhibition. The primary ...