Synthesis and antitumor activity of 1-β-D-arabinofuranosylcytosine conjugates of optical isomers of ether and thioether lipids |
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Authors: | Chung Hong II Seung-Ho An Alexander Nechaev Alan J Kirisits Rakesh Vig Charles R West |
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Affiliation: | (1) Department of Neurosurgery, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263 Buffalo, NY;(2) Present address: Cheil Foods & Chemicals, 522-1 Dokpyong-ri, Majang-myon, Ichon-kun, Kyonggi-do, Korea |
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Abstract: | Four 1-β-D-arabinofuranosylcytosine conjugates (ara-C) (1a, b and 2a, b) ofsn−1 andsn−3 isomers of 1-O-octadecyl-2-O-palmitoylglycerol and its 1-S-alkyl analogue have been synthesized, and their antitumor activity against L1210 lymphoid leukemia in mice were compared
with those of the previous conjugates (3a, b) of racemates in order to determine the significance of chirality of the glycerol
moieties for activity. Administration (i.p.) of a single dose (300 mg/kg) of conjugates ofsn−1 (1a),sn−3 (2a) andrac (3a) isomers of the ether lipid increased lifespan of i.p. implanted L1210 lymphoid leukemic DBA/2J mice by 169, 175 and
236%, respectively. Thesn−1 (1b),sn−3 (2b), andrac (3b) isomers of the thioether lipid with a single dose of 300 mg/kg produced an increase in lifespan values of 238, 263 and
250%, respectively. The results indicate that chirality of the glycerol moieties appears not to be critical for the activity,
and racemates 3a and 3b are promising prodrugs of ara-C for further clinical investigations.
This material was presented in part at the 81 st Annual Meeting of the American Association for Cancer Research in Washington,
D.C., May, 1990 (Abstract No. 2493). |
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