Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity
- Eur J Med Chem. 2009 Mar;44(3):1172-9. doi: 10.1016/j.ejmech.2008.06.002.
- 1. Institut für Radiopharmazie, Forschungszentrum Dresden-Rossendorf, Postfach 510119, 01314 Dresden, Germany.
The antiproliferative activity screening on human tumor cell lines of a series of modified uracil and cytosine Bases as well as some corresponding acyclonucleosides, and comparison of structure-activity relationship revealed the importance of chemical reactivity of the substituent attached to the C5-position of uracil for the activity of studied compounds. Namely, the results obtained for the most active compounds, 5-(chloroacetylamino)uracil (2) and its acyclic sugar analogue 18, suggest that formation of a covalent bond between reactive substituent and several possible targets within the Thymidylate Synthase mechanism (sulphur of the cysteine residue, basic part of the enzyme, N,N-methylene tetrahydrofolate or its reactive iminium forms) is the most probable mode of action. In addition, novel C5-substituted uracil derivative 6 (5-[bis-(2-p-methoxybenzylthioethyl)amine]acetylaminouracil) exhibited high antiproliferative activity against HeLa and MiaPaCa-2 cell lines, by an as yet unknown mechanism.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Nucleoside Antimetabolite/AnalogResearch Areas: Cancer