Synthesis of 3'-beta-carbamoylmethylcytidine (CAMC) and its derivatives as potential antitumor agents.
3'-beta-Carbamoylmethylcytidine (CAMC) and its derivatives were synthesized using an intramolecular Reformatsky-type reaction promoted by SmI2 as the key step. In vitro tumor cell growth inhibitory activity was evaluated and CAMC was found to exhibit potent cytotoxicity against various human tumor cell lines. From a structure-activity relationship study it was postulated that the cytotoxic mechanism of action of CAMC did not require phosphorylation at the 5'-hydroxyl group. This study provides a novel strategy for the development of a new type of antitumor nucleoside.
Ichikawa
Satoshi
S
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.
Minakawa
Noriaki
N
Shuto
Satoshi
S
Tanaka
Motohiro
M
Sasaki
Takuma
T
Matsuda
Akira
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation
C522214:3'-beta-carbamoylmethylcytidine; D000970:Antineoplastic Agents; D002219:Carbamates; D007202:Indicators and Reagents; C513402:2'-C-methylcytidine; D003562:Cytidine