Document 0568
 DOCN  M9440568
 TI    Antiviral activity of 2',3'-dideoxy-beta-L-5-fluorocytidine
       (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC) against
       hepatitis B virus and human immunodeficiency virus type 1 in vitro.
 DT    9404
 AU    Lin TS; Luo MZ; Liu MC; Pai SB; Dutschman GE; Cheng YC; Department of
       Pharmacology and the Comprehensive Cancer Center,; Yale University
       School of Medicine, New Haven, CT 06510.
 SO    Biochem Pharmacol. 1994 Jan 20;47(2):171-4. Unique Identifier : AIDSLINE
       MED/94137264
 AB    2',3'-Dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and
       2',3'-dideoxy-beta-L-cytidine (beta-L-ddC), two nucleosides with
       unnatural L-configuration, have been synthesized and found to have
       potent antiviral activity against hepatitis B virus (HBV) and human
       immunodeficiency virus type 1 (HIV-1) in vitro with very little
       toxicity. At 1 microM, both beta-L-ddC and beta-L-FddC inhibited the
       growth of HBV by more than 90%, while at the same concentration the
       D-configuration counterparts, 2',3'-dideoxy-beta-D-cytidine (ddC) and
       2',3'-dideoxy-beta-D-5-fluorocytidine (beta-D-FddC), did not show
       antiviral activity against HBV. The order of anti-HIV-1 activity was
       beta-L-FddC > ddC; beta-D-FddC > beta-L-ddC. The dose-limiting toxicity
       of ddC is neuropathy which is believed to be caused by the inhibition of
       the synthesis of mitochondrial DNA. ddC severely inhibited the
       mitochondrial DNA synthesis of CEM cells yielding an IC50 value of 0.022
       microM. Conversely, both beta-L-FddC and beta-L-ddC did not demonstrate
       any inhibition against mitochondrial DNA synthesis up to 100 microM
       concentration.
 DE    Antiviral Agents/*PHARMACOLOGY  Cells, Cultured/DRUG EFFECTS
       Comparative Study  DNA/BIOSYNTHESIS  Hepatitis B/MICROBIOLOGY  Hepatitis
       B Virus/*DRUG EFFECTS  HIV-1/*DRUG EFFECTS  Stereoisomers  Support, U.S.
       Gov't, P.H.S.  Virus Replication/DRUG EFFECTS  Zalcitabine/*ANALOGS &
       DERIVATIVES/CHEMICAL SYNTHESIS/  *PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).