Cell-dependent interference of a series of new 6-aminoquinolone derivatives with viral (HIV/CMV) transactivation
In: Journal of antimicrobial chemotherapy (Print), Jg. 56 (2005), Heft 5, S. 847-855
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academicJournal
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Zugriff:
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-a 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.
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Cell-dependent interference of a series of new 6-aminoquinolone derivatives with viral (HIV/CMV) transactivation
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Autor/in / Beteiligte Person: | STEVENS, Miguel ; BALZARINI, Jan ; TABARRINI, Oriana ; ANDREI, Graciela ; SNOECK, Robert ; CECCHETTI, Violetta ; FRAVOLINI, Arnaldo ; DE CLERCQ, Erik ; PANNECOUQUE, Christophe |
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Zeitschrift: | Journal of antimicrobial chemotherapy (Print), Jg. 56 (2005), Heft 5, S. 847-855 |
Veröffentlichung: | Oxford: Oxford University Press, 2005 |
Medientyp: | academicJournal |
Umfang: | print, 31 ref |
ISSN: | 0305-7453 (print) |
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