Synthesis and biological activity of 2-fluoro adenine and 6-methyl purine nucleoside analogs as prodrugs for suicide gene therapy of cancer.
A novel series of 6-methylpurine nucleoside derivatives with substitutions at 5-position have been synthesised These compounds bear a 5'-heterocycle such as triazole or a imidazole with a two carbon chain, and an ether, thio ether or amine. To extend the SAR study of 2-fluoroadenine and 6-methyl purine nucleosides, their corresponding alpha-linker nucleosides with L-xylose and L-lyxose were also synthesized. All of these compounds have been evaluated for their substrate activity with E. coli PNP.
Silamkoti
A V
AV
Southern Research Institute, Birmingham, AL 35255-5305, USA.
Allan
P W
PW
Hassan
A E A
AE
Fowler
A T
AT
Sorscher
E J
EJ
Parker
W B
WB
Secrist
J A
JA
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008956:Models, Chemical; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D011684:Purine Nucleosides / Q000737:chemistry; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry; D011687:Purines / Q000737:chemistry*; D013379:Substrate Specificity; D014994:Xylose / Q000737:chemistry
D000970:Antineoplastic Agents; D009705:Nucleosides; D011355:Prodrugs; D011684:Purine Nucleosides; D011687:Purines; C016588:6-methylpurine; C038208:2-fluoroadenine; D002244:Carbon; D014994:Xylose; D011683:Purine-Nucleoside Phosphorylase; D000225:Adenine