RT Journal Article
SR Electronic
T1 Antiviral, antimetabolic, and cytotoxic activities of 5-substituted 2'-deoxycytidines.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 217
OP 223
VO 21
IS 1
A1 E De Clercq
A1 J Balzarini
A1 J Descamps
A1 G F Huang
A1 P F Torrence
A1 D E Bergstrom
A1 A S Jones
A1 P Serafinowski
A1 G Verhelst
A1 R T Walker
YR 1982
UL http://molpharm.aspetjournals.org/content/21/1/217.abstract
AB Various 5-substituted 2'-deoxycytidines, including 5-bromo-dCyd, 5-iodo-dCyd, 5-nitro-dCyd, 5-ethynyl-dCyd, 5-propyl-dCyd, (E)-5-(2-bromovinyl)-dCyd, and (E)-5-(2-iodovinyl)-dCyd, were evaluated for their antiviral and antimetabolic properties in primary rabbit kidney (PRK) cell cultures and for their inhibitory effects on murine L1210 cell proliferation. All dCyd analogues proved to be selective inhibitors of herpes simplex virus (HSV) replication: 5-bromo-dCyd, 5-iodo-dCyd, 5-nitro-dCyd, and 5-ethynyl-dCyd were more selective in their anti-HSV activity than were the corresponding 5-substituted 2'-deoxyuridines, whereas 5-propyl-dCyd, (E)-5-(2-bromovinyl)-dCyd, and (E)-5-(2-iodovinyl)-dCyd were as selective as their dUrd counterparts. The dCyd analogues were also less cytotoxic (for both PRK and L1210 cells), as could be monitored by inhibition of either cell proliferation or host-cell DNA synthesis (incorporation of radiolabeled precursors). Of all 5-substituted 2'-deoxycytidines tested, the (E)-5-(2-halogenovinyl) derivatives emerged as the most potent and most selective inhibitors of HSV (Type 1) replication.