Synthesis and properties of lipophilic derivatives of 5-fluorouracil |
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Authors: | A V Semakov A A Blinkov G P Gaenko A G Vostrova J G Molotkovsky |
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Institution: | 16472. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia
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Abstract: | 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. |
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