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. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Cell-dependent interference of a series of new 6-aminoquinolone derivatives with viral (HIV/CMV) transactivation.
TABARRINI, Oriana;CECCHETTI, Violetta;FRAVOLINI, Arnaldo;
2005
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-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. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
