Abstract
Novel non-nucleobase-derived inhibitors of the angiogenic enzyme, thymidine phosphorylase, have been identified using molecular modelling, synthesis and biological evaluation. These inhibitors are 2,4,5-trioxoimidazolidines bearing N-(substituted)phenylalkyl groups, together with, in most cases, N′-(CH2)n-carboxylic acid, ester or amide side chains. The best compound from this series is 3-(2,4,5-trioxo-3-phenylethyl- imidazolodin-1-yl)propionamide, with an IC50 of 40 μM against Escherichia coli TP. Molecular modelling suggests that this ligand, when complexed with closed-cleft human TP, would have the phenylalkyl group in the active site region normally occupied by a thymine-containing structure. © 2011 Elsevier Masson SAS. All rights reserved.
Original language | English |
---|---|
Pages (from-to) | 1165-1171 |
Number of pages | 6 |
Journal | European Journal of Medicinal Chemistry |
Volume | 46 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2011 |
Keywords
- Anti-angiogenic
- Hydantoin
- Molecular modelling
- Parabanic acid
- Thymidine phosphorylase
- Trioxoimidazolidine