Journal Article

Cell-dependent interference of a series of new 6-aminoquinolone derivatives with viral (HIV/CMV) transactivation

Miguel Stevens, Jan Balzarini, Oriana Tabarrini, Graciela Andrei, Robert Snoeck, Violetta Cecchetti, Arnaldo Fravolini, Erik De Clercq and Christophe Pannecouque

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 5, pages 847-855
Published in print November 2005 | ISSN: 0305-7453
Published online September 2005 | e-ISSN: 1460-2091 | DOI:
Cell-dependent interference of a series of new 6-aminoquinolone derivatives with viral (HIV/CMV) transactivation

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  • Medical Oncology
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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-α)- 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-α release from PMA-induced OM-10.1 cells but allowed TNF-α 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-1α 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.

Keywords: Tat; TAR; latency

Journal Article.  5275 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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