Synthesis and cytostatic and antiviral activities of 1-beta-D-ribofuranosyl-5-alkylcytosine (5-alkylcytidine) cyclic 3',5'-monophosphates.
A series of 5-alkylcytidines and their 5'-monophosphates and cyclic 3',5'-monophosphates have been synthesized and evaluated for antiviral and antitumor activity. The 5-alkyl cyclic nucleotides were not cytostatic (ID50 greater than 200 micrograms/mL) against leukemia L1210 cells and a deoxycytidine kinase-deficient subline thereof. Certain of the corresponding nucleosides and their 5'-monophosphates did show activity within the range of 35-162 micrograms/mL, as did the unsubstituted cytidine cyclic 3',5'-monophosphate. No antiviral activity was found for any of the compounds at 400 micrograms/mL. A drug design rationale for utilization of 5-alkylcytidines based on their potential conversion to biologically active 5-alkyl-2'-deoxyuridines is not supported by these experimental findings.
Béres
J
J
Department of Chemistry, University of Utah, Salt Lake City 84112.
Bentrude
W G
WG
Otvös
L
L
Balzarini
J
J
De Clercq
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D003563:Cyclic CMP / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D003597:Cytosine Nucleotides / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003597:Cytosine Nucleotides; D003563:Cyclic CMP; D011494:Protein Kinases