Document 0812
 DOCN  M94B0812
 TI    Anti-human immunodeficiency virus activities of the beta-L enantiomer of
       2',3'-dideoxycytidine and its 5-fluoro derivative in vitro.
 DT    9412
 AU    Gosselin G; Schinazi RF; Sommadossi JP; Mathe C; Bergogne MC; Aubertin
       AM; Kirn A; Imbach JL; Laboratoire de Chimie Bioorganique, URA Centre
       National de la; Recherche Scientifique 488, Universite de Montpellier
       II,; Sciences et Techniques du Languedoc, France.
 SO    Antimicrob Agents Chemother. 1994 Jun;38(6):1292-7. Unique Identifier :
       AIDSLINE MED/94379781
 AB    The L enantiomer of 2',3'-dideoxycytidine (DDC) was recently shown to
       inhibit selectively human immunodeficiency virus type 1 (HIV-1) in
       vitro. In the current study, the potent anti-HIV activity of L-DDC was
       confirmed and extended to several HIV-1 and HIV-2 strains in various
       cell culture systems, including primary human lymphocytes and
       macrophages. Furthermore, its 5-fluoro congener,
       beta-L-2',3'-dideoxy-5-fluorocytidine (L-FDDC), was found to have more
       potent anti-HIV activity and a higher therapeutic index in acutely
       infected human peripheral blood mononuclear cells. These compounds had
       no marked activity against HIV-1 isolates resistant to the oxathiolane
       pyrimidine nucleosides (-)-beta-L-2',3'-dideoxy-5-fluoro-3'-thiacytidine
       [(-)-FTC] and (-)-beta-L-2',3'-dideoxy-3'-thiacytidine, but
       3'-azido-3'-deoxythymidine (AZT)-resistant viruses were susceptible to
       L-DDC and L-FDDC. Cytotoxicity studies with human myeloid progenitor
       cells indicated that L-DDC and L-FDDC had median inhibitory
       concentrations comparable to those of AZT, DDC, and FDDC, but L-DDC and
       L-FDDC were significantly less toxic than AZT, DDC, and FDDC when
       erythroid progenitor cells were used. L-FDDC had the highest selectivity
       indices (6,000 and 9,000 for erythroid and myeloid progenitor cells,
       respectively) of all the compounds evaluated. Further preclinical
       development of L-FDDC is warranted in order to determine its potential
       usefulness in the treatment of HIV infections.
 DE    Antiviral Agents/*PHARMACOLOGY  Bone Marrow/DRUG EFFECTS  Cell Line
       Drug Resistance  Human  HIV/*DRUG EFFECTS  Stereoisomers  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't,
       P.H.S.  Zalcitabine/*ANALOGS & DERIVATIVES/*PHARMACOLOGY/TOXICITY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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