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Synthese von 4‐Alkylcytosinnucleosiden und deren cytostatische Wirkung im L1210 Leukämiemodell der Maus
Author(s) -
Schott Herbert,
Häussler Markus P.,
Schwendener Reto A.
Publication year - 1994
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.15619940504
Subject(s) - chemistry , uracil , l1210 cells , residue (chemistry) , cytosine , nucleoside , deoxyribose , stereochemistry , nucleoside analogue , ribose , nucleic acid , biochemistry , cytotoxicity , in vitro , dna , enzyme
Synthesis of 4‐Alkylcytosine Nucleosides and Evaluation of Cytostatic Activity in the L1210 Murine Leukemia 4‐Alkylcytosine nucleosides 2 were prepared by nucleophilic substitution of the 4‐(1, 2, 4‐triazol‐1‐yl) residue of uracil nucleoside derivatives 1 using different amino compounds. The antitumor activity against L1210 murine leukemia of fifteen 4‐alkylcytosine nucleosides dissolved in buffer or incorporated into liposomes was tested. Liposomal 1‐(β‐ D ‐arabinofuranosyl)‐4‐octadecylamino‐2(1 H ) ‐pyrimidinone ( 2d ) having the highest activity gave an increase of life span (ILS) of 706% and 6/6 survivors at 400 μmol/kg. The structurally related and well‐known antitumor drug 1‐(β‐ D ‐arabinofuranosyl)cytosine (araC) dissolved in buffer gave only 179% ILS and 0/6 survivors under corresponding conditions. Derivatives 2a‐c and 2e‐f having shorter or longer alkyl chains were less active. All the other derivatives showed no antitumor effect. The activity of the 4‐alkylcytosine nucleoside was also lost, when the arabinose residue was replaced by ribose or deoxyribose.