Monophosphoric acid diesters of 7 beta-hydroxycholesterol and of pyrimidine nucleosides as potential antitumor agents: synthesis and preliminary evaluation of antitumor activity.
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.
Ji
Y H
YH
Laboratoire de Chimie Organique des Substances Naturelles, URA CNRS No. 31, Strasbourg, France.
Moog
C
C
Schmitt
G
G
Bischoff
P
P
Luu
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002287:Carcinoma, Krebs 2 / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003856:Deoxyuracil Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006888:Hydroxycholesterols / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D010766:Phosphorylation; D011741:Pyrimidine Nucleosides; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003856:Deoxyuracil Nucleotides; D006888:Hydroxycholesterols; D011741:Pyrimidine Nucleosides; C011724:cholest-5-en-3 beta,7 alpha-diol