2'-C-cyano-2'-deoxy-1-β-D-arabinofuranosyl-cytosine (CNDAC): A mechanism-based DNA-strand-breaking antitumor nucleoside

Article abstract of DOI:10.1080/15257779508012407

The antitumor mechanism of action of 2'-C-cyano-2'-deoxy-1-β-D- arabinofuranosyl (CNDAC) has been examined. CNDAC was designed as a potentially DNA-self-strand-breaking nucleoside. It had potent antitumor effects against various solid tumors in vitro as well as in vivo. Using a chain-extension method with Vent (exo^-) DNA polymerase and a short primer/template system, we found that 5'-triphosphate of CNDAC (CNDACTP) was incorporated into the primer at a site opposite a guanine residue in the template. After further chain-extension reaction of the primer containing CNDAC at the 3'-terminus, chain elongation was not observed. Therefore, CNDACTP appeared to act as a chain-terminator. Analyses of the structure of the 3'-terminus in the primer revealed 2'-C-cyano-2',3'-didehydro-2',3'- dideoxycytidine (ddCNC) together with CNDAC and 2'-C-cyano-2'-deoxy-1-β-D- ribofuranosylcytosine (CNDC). The existence of ddCNC in the 3'-end of the primer would be due to the self-strand-break by the nucleotide incorporated next to CNDAC. We also found that CNDAC was epimerized to CNDC in near- neutral to alkaline media. Therefore, CNDC found in the primer was epimerized after incorporation of CNDACTP into the primer. We also described the metabolism of CNDAC.

Full text of DOI:10.1080/15257779508012407

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2′-C-Cyano-2′-deoxy-1-β-D-
arabinofuranosylcytosine (CNDAC): A
Mechanism-Based DNA-Strand-Breaking
Antitumor Nucleoside1
Akira Matsuda a & Atsushi Azuma a
a Faculty of Pharmaceutical Sciences , Hokkaido University , Kita-12,
Nishi-6, Kita-ku, Sapporo, 060, Japan
Published online: 16 Feb 2007.
To cite this article: Akira Matsuda & Atsushi Azuma (1995) 2′-C-Cyano-2′-deoxy-1-β-D-
arabinofuranosylcytosine (CNDAC): A Mechanism-Based DNA-Strand-Breaking Antitumor Nucleoside1 ,
Nucleosides and Nucleotides, 14:3-5, 461-471
To link to this article: http://dx.doi.org/10.1080/15257779508012407
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