Inhibition of retrovirus-induced syncytium formation by photoproducts of a brominated 1,8-naphthalimide compound.
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.
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228.
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TC
Chanh
D E
DE
Lewis
M M
MM
Judy
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Sogandares-Bernal
G R
GR
Michalek
R E
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Utecht
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Skiles
S C
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Chang
J L
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Matthews
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects / Q000633:toxicity; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D015726:Giant Cells / Q000187:drug effects* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053644:Naphthalimides; D010777:Photochemistry
C091895:3-bromo-4-(hexylamino)-N-hexyl-1,8-naphthalimide; D000998:Antiviral Agents; D053644:Naphthalimides; D015057:1-Naphthylamine