Synthesis and antiviral and cytostatic properties of 3'-deoxy-3'-fluoro- and 2'-azido-3'-fluoro-2',3'-dideoxy-D-ribofuranosides of natural heterocyclic bases.
A series of 3'-deoxy-3'-fluoro- and 2'-azido-2',3'-dideoxy-3'-fluoro-D-ribofuranosides of natural heterocyclic bases have been synthesized with the use of universal carbohydrate precursors, viz., 1-O-acetyl-2,5-di-O-benzoyl-3-deoxy-3-fluoro-D-ribofuranose and methyl 2-azido-5-O-benzoyl-2,3-dideoxy-3-fluoro-beta-D-ribofuranoside, respectively. The cytostatic and antiviral activity of the compounds was evaluated against a variety of tumor cell lines and DNA/RNA viruses, respectively. As the most active compound, from both a cytostatic and antiviral activity viewpoint, emerged 3'-deoxy-3'-fluoroadenosine. It inhibited the proliferation of some tumor cell lines (i.e. murine leukemia L1210 and human T-lymphocyte MT-4) at a concentration of 0.2-2 micrograms/mL, and proved inhibitory to the replication of positive-stranded RNA viruses (i.e. polio, Coxsackie, Sindbis, Semliki forest), double-stranded RNA viruses (i.e. reo), and some DNA viruses (i.e. vaccinia) at a concentration of 1-4 micrograms/mL, which is well below the cytotoxicity threshold (40 micrograms/mL).
Mikhailopulo
I A
IA
Institute of Bioorganic Chemistry, Byelorussian Academy of Sciences, Minsk, USSR.
Poopeiko
N E
NE
Pricota
T I
TI
Sivets
G G
GG
Kvasyuk
E I
EI
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D002522:Chlorocebus aethiops; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D015224:Dideoxynucleosides; D006845:Hydrocarbons, Fluorinated