Document 0264
 DOCN  M9550264
 TI    Inhibition of retrovirus-induced syncytium formation by photoproducts of
       a brominated 1,8-naphthalimide compound.
 DT    9505
 AU    Chanh TC; Lewis DE; Judy MM; Sogandares-Bernal F; Michalek GR; Utecht
       RE; Skiles H; Chang SC; Matthews JL; Department of Virology and
       Immunology, Southwest Foundation for; Biomedical Research, San Antonio,
       TX 78228.
 SO    Antiviral Res. 1994 Oct;25(2):133-46. Unique Identifier : AIDSLINE
       MED/95150556
 AB    A major disadvantage of conventional phototherapy is the requirement for
       the in situ delivery of stimulating photoenergy subsequent to the
       binding of photochemicals to target malignant cells, or virus-infected
       cells, or viruses. This drawback has resulted in considerable limitation
       in the use of photochemicals in photomedicine. To circumvent this
       problem, we have investigated the antiviral efficacy of a brominated
       1,8-naphthalimide photocompound, termed LY66Br
       [3-bromo-4-(hexylamino)-N-hexyl-1,8-naphthalimide], which upon exposure
       to visible light at 420 nm generates independently of oxygen one or more
       stable antiviral molecular photoproducts (e.g., is 'preactivated').
       Human cell lines infected with the human immunodeficiency virus type 1
       (HIV-1), or with the human T-lymphotropic virus type-1 (HTLV-I) exposed
       to photochemical products of LY66Br (P-LY66Br) completely lost their
       ability to form syncytia in vitro. Photoproducts of P-LY66Br retain full
       antiviral activity for at least 3 and 6 weeks when stored at room
       temperature and at -80 degrees C, respectively. Concentrations of
       P-LY66Br, effective in inhibiting syncytium formation mediated by HIV-1
       and HTLV-I, were nontoxic to normal red cell components of whole blood
       (red blood cell 2,3-diphosphoglyceric acid, adenosine triphosphate,
       osmotic fragility or blood type antigens). Additionally, no evidence of
       acute toxicity was demonstrated in mice following an intravenous bolus
       inoculation to achieve plasma concentration of 600 microM of P-LY66Br.
       These findings represent the first demonstration of inhibition of
       retrovirus-induced syncytium formation by a photochemical product, and
       justify further investigation of the preactivation process of
       photochemicals in the treatment of systemic viral infections such as the
       acquired immunodeficiency syndrome (AIDS), in cancer therapy, and in
       sterilization of banked blood products.
 DE    Animal  Antiviral Agents/CHEMICAL SYNTHESIS/*PHARMACOLOGY/RADIATION
       EFFECTS/TOXICITY  Cytopathogenic Effect, Viral/*DRUG EFFECTS
       Erythrocytes/DRUG EFFECTS  Female  Giant Cells/*DRUG EFFECTS/VIROLOGY
       HIV-1/*DRUG EFFECTS/PHYSIOLOGY  HTLV-I/*DRUG EFFECTS/PHYSIOLOGY  Male
       Mice  Mice, Inbred BALB C  Photochemistry  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  1-Naphthylamine/*ANALOGS &
       DERIVATIVES/CHEMICAL SYNTHESIS/  PHARMACOLOGY/RADIATION EFFECTS/TOXICITY
       JOURNAL ARTICLE

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