Acetylenic nucleosides. 4. 1-beta-D-arabinofuranosyl-5-ethynylcytosine. Improved synthesis and evaluation of biochemical and antiviral properties.
5-Ethynyl-1-beta-D-arabinofuranosylcytosine (EAC) was prepared from 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)cytosine by iodination followed by coupling with (trimethylsilyl)acetylene and deblocking. At 50 microM, EAC was found to inhibit the in vitro replication of herpes simplex virus type 1 and type 2 by greater than 99%. EAC also showed activity against a strain of HSV-1 resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine which has an alteration of the virus-induced thymidine kinase (TK). At 100 microM, EAC did not inhibit the in vitro growth of leukemia L1210 and HeLa cells. EAC was resistant to the action of dCR-CR deaminase, its rate of deamination being approximately 2% that of dCR. The compound was a poor substrate for dCR kinase, but it was phosphorylated by HSV-1- and HSV-2-induced TKs at 50% and 30%, respectively, the rate of thymidine.
Bobek
M
M
Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Kavai
I
I
Sharma
R A
RA
Grill
S
S
Dutschman
G
G
Cheng
Y C
YC
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D003641:Deamination; D010766:Phosphorylation; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; D003561:Cytarabine; C054004:1-arabinofuranosyl-5-ethynylcytosine