Synthesis and anti-cancer activity of some novel 5-azacytosine nucleosides.
1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine to obtain alpha and beta anomers of nucleosides. All four nucleosides were reduced to the corresponding dihydro derivatives and deblocked to give target compounds. All eight target compounds were evaluated in a series of human cancer cell lines in culture. Only 2'-deoxy-4'-thio-5-azacytidine (3beta) was found to be cytotoxic in all the cell lines and was further evaluated in vivo. Details of the synthesis and biological activity are reported.
Tiwari
Kamal N
KN
Southern Research Institute, Birmingham, Alabama 35255-5305, USA.
Cappellacci
Loredana
L
Montgomery
John A
JA
Secrist
John A
JA
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002236:Carbohydrate Conformation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003562:Cytidine / Q000031:analogs & derivatives; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010429:Pentoses / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology; D013457:Sulfur Compounds / Q000737:chemistry
C120717:4-thio-2-deoxy-pentofuranose; D000970:Antineoplastic Agents; D010429:Pentoses; D011741:Pyrimidine Nucleosides; D013457:Sulfur Compounds; C039854:5-azacytosine; D003562:Cytidine; D003596:Cytosine; D001374:Azacitidine