In vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine.

Abstract

The in vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine (4'-thio-DMDC), was examined. 4'-Thio-DMDC inhibited the growth of various cell lines established from human solid cancers, particularly the growth of lung and bladder carcinomas and melanomas. 4'-Thio-DMDC exhibited potent antitumor activity against subcutaneously implanted murine sarcoma S-180 and human fibrosarcoma HT-1080 xenografts. It was shown that 4'-thio-DMDC suppressed cell growth by inhibiting cellular DNA synthesis, and phosphorylation of the 5'-position of its deoxyribose by deoxycytidine kinase was needed for its antitumor activity. 4'-Thio-DMDC is a poor substrate for cytidine deaminase, thus it is a promising agent for the treatment of malignant solid tumors because it will not be converted into its inactive uridine form.

• Authors: S Miura, M Tanaka, Y Yoshimura, H Satoh, S Sakata, H Machida, A Matsuda, T Sasaki
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 19 Issue 10 Pg. 1311-5 (Oct 1996) ISSN: 0918-6158 [Print] Japan
• PMID: 8913503 (Publication Type: Journal Article)

Chemical References

• 4'-thio-2'-deoxy-2'-methylidenecytidine
• Antineoplastic Agents
• Thionucleosides
• Deoxycytidine
• RNA
• Cytidine Deaminase
• 2'-deoxy-2'-methylenecytidine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cytidine Deaminase (metabolism)
• DNA Replication (drug effects)
• Deoxycytidine (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Female
• Humans
• Mice
• Phosphorylation
• Protein Biosynthesis
• RNA (biosynthesis)
• Thionucleosides (chemical synthesis, pharmacology)
• Tumor Cells, Cultured (drug effects)