Neutralization of HIV-1 and inhibition of HIV-1-induced syncytia by 1,8-naphthalimide photoactive compound.
The antiviral property of a newly designed class of 1,8-naphthalimide photochemical compounds was investigated. One such photoactive compound, 1,14-bis-(N-hexyl-3'-bromo-1,8'-naphthalimide-4'-yl)-1,4,11,14- tetraazatetradecane-5,10-dione (diED66Br), when activated to an excited state by visible light (420 nm), effectively neutralized the in vitro infectivity of human immunodeficiency virus (HIV-1). Light-activated diED66Br also inhibited syncytium formation induced by cells infected with HIV-1. Nonactivated diED66Br was completely ineffective. The neutralizing and syncytium-inhibiting doses of activated diED66Br had no effect on normal human peripheral blood mononuclear cells. Radioimmunoprecipitation analysis indicated that diED66Br neutralizing activity resulted primarily from its ability to inhibit the binding of HIV-1 envelope glycoprotein gp120 to the CD4 cellular receptors. Although the exact molecular mechanism of viral neutralization by diED66Br has not been elucidated, its ability to neutralize HIV-1 infectivity and to inhibit syncytium formation supports further investigations of this photochemical as a potential therapeutic treatment of HIV-1 infection.
Chanh
T C
TC
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228.
Lewis
D E
DE
Allan
J S
JS
Sogandares-Bernal
F
F
Judy
M M
MM
Utecht
R E
RE
Matthews
J L
JL
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000528:radiation effects; D000998:Antiviral Agents / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D016655:HIV Core Protein p24 / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D053644:Naphthalimides; D010777:Photochemistry; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D053644:Naphthalimides; C084861:1,14-bis-(N-hexyl-3'-bromo-1,8'-naphthalimide-4'-yl)-1,4,11,14-tetraazatetradecane-5,10-dione; D015057:1-Naphthylamine