Title: Cell-dependent interference of a series of new 6-aminoquinolone derivatives with viral (HIV/CMV) transactivation
Authors: Stevens, Miguel ×
Balzarini, Jan
Tabarrini, Oriana
Andrei, Graciela
Snoeck, Robert
Cecchetti, Violetta
Fravolini, Arnaldo
De Clercq, Erik
Pannecouque, Christophe #
Issue Date: Nov-2005
Publisher: Oxford University Press
Series Title: The Journal of Antimicrobial Chemotherapy vol:56 issue:5 pages:847-855
Abstract: OBJECTIVES: Quinolone derivatives have been shown to inhibit human immunodeficiency virus (HIV) replication at the transcriptional level. Recently, a series of new 6-aminoquinolones that are endowed with more pronounced anti-HIV activities compared with the formerly reported quinolone derivatives have been published. These potent 6-aminoquinolones were further evaluated for their broad-spectrum antiviral properties. METHODS: Latently HIV-1-infected cell lines as well as cytomegalovirus (CMV)-infected fibroblasts were used to evaluate the antiviral potency of the 6-aminoquinolone derivatives. Additionally green fluorescent protein (GFP) transactivation experiments using different promoters were conducted. RESULTS: The compounds completely suppressed tumour necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 expression in latently HIV-1-infected OM-10.1 and U1 cell lines at non-toxic concentrations. In addition, HIV-1 mRNA production was dramatically suppressed in both cell lines in a dose-dependent manner. In the same concentration range, the compounds inhibited TNF-alpha release from PMA-induced OM-10.1 cells but allowed TNF-alpha production from PMA-induced U1 cells at all concentrations tested. The 6-aminoquinolone derivatives were not only inhibitory to the Tat-mediated transactivation of the HIV-1 LTR promoter, but were also found to interfere in a cell-dependent way with the transactivation process mediated from the human CMV immediate early and the human EF-1alpha promoter. Additionally, the 6-aminoquinolone derivatives were also found to be inhibitory to CMV replication in fibroblast cells. CONCLUSIONS: It thus appears that the antiviral spectrum of this class of compounds is not confined to the specific inhibition of HIV but encompasses CMV as well. This broad-spectrum activity window might provide an interesting platform for future applications for the 6-aminoquinolone derivatives.
ISSN: 0305-7453
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Department of Microbiology & Immunology - miscellaneous
× corresponding author
# (joint) last author

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