Abstract
7 beta-Hydroxycholesterol, which has been shown to be selectively cytotoxic toward tumor cells cultured in vitro, was converted into the corresponding water-soluble phosphoric acid ester and linked to a pyrimidine nucleoside such as 5-fluoro-2'-deoxyuridine or 2'-deoxyuridine. 2-Chlorophenyl phosphorodichloridate (3), without activation, was used directly to phosphorylate the protected oxygenated sterol. The intermediate phosphorylated the 5'-OH group of nucleoside selectively, leading to compounds 1a and 1b after deprotection. These compounds were screened for their antiproliferative activity toward EL-4 murine leukemia cells in vitro and for their antitumor activity against the mice bearing Krebs II ascitic carcinoma in vivo.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / therapeutic use
-
Carcinoma, Krebs 2 / drug therapy
-
Cell Division / drug effects
-
Chemical Phenomena
-
Chemistry
-
Deoxyuracil Nucleotides / chemical synthesis*
-
Deoxyuracil Nucleotides / pharmacology
-
Deoxyuracil Nucleotides / therapeutic use
-
Female
-
Hydroxycholesterols* / chemical synthesis*
-
Hydroxycholesterols* / pharmacology
-
Hydroxycholesterols* / therapeutic use
-
Leukemia, Experimental / drug therapy
-
Leukemia, Experimental / pathology
-
Mice
-
Molecular Structure
-
Phosphorylation
-
Pyrimidine Nucleosides*
-
Tumor Cells, Cultured
Substances
-
Antineoplastic Agents
-
Deoxyuracil Nucleotides
-
Hydroxycholesterols
-
Pyrimidine Nucleosides
-
cholest-5-en-3 beta,7 alpha-diol