Synthesis and properties of lipophilic derivatives of 5-fluorouracil

Autor: Jul.G. Molotkovsky, A. V. Semakov, A. G. Vostrova, G. P. Gaenko, A. A. Blinkov
Rok vydání: 2013
Předmět:
Zdroj: Russian Journal of Bioorganic Chemistry. 39:299-305
ISSN: 1608-330X
1068-1620
DOI: 10.1134/s1068162013030138
Popis: A series of N 1-acyl derivatives of 5-fluorouracil (5-FU) bearing the residues of palmitic, p-myristoylaminobenzoic, p-oleoylaminobenzoic, and adamantane-1-carboxylic acids have been synthesized. The relative hydrolysis rates for the derivatives under physiological conditions (pH 7.2 and 37°C) have been determined, and it has been shown that the resistance of these compounds to hydrolysis increases as the steric accessibility of the amide group at residue N 1 of 5-FU decreases. The derivatives easily incorporate into the lipid bilayer; their liposomal preparations show a marked cytostatic activity on human breast lymphoma cells (LD50 ∼1 μM) and are of interest as potential antitumor preparations. In addition, a fluorescent analogue of the above derivatives, 1-[8-(3-perylenyl)octanoyl]-5-fluorouracil, has been synthesized, which is intended for studying the behavior of 5-FU derivatives in cells and tissues by instrumental methods.
Databáze: OpenAIRE
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