The inhibitory activity of several fluoroquinolone antibiotics against human immunodeficiency virus type 1 (HIV-1) replication was investigated. R-71762, (±) 9-fluoro-3-fluoromethyl-2,3-dihydro-10-[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, protected MT-4 cells from HIV-1-induced cytopathic effects. Furthermore, the compound inhibited virus replication both in acutely and in chronically HIV-1-infected cells. On the other hand, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin and enoxacin, that were previously reported to be protective against HIV-1-induced cytopathic effects, did not show any protective activity in our assay system. These results indicate that R-71762 is a novel inhibitor of HIV-1 replication and is effective even in HIV-1 chronically infected cells.
ABSTRACT. The inhibitory activities of various 8-difluoromethoxy-4-quinolone derivatives against feline immunodeficiency virus (FIV) replication in the chronically infected cell line P-CrFK were investigated. Certain derivatives were found to inhibit FIV production from PCrFK cells in a dose-dependent manner without exhibiting cytotoxic effects at inhibitory concentrations. Based on this study, the structures important for anti-FIV activity are suggested to be (i) a carboxyl group at position C-3, and (ii) an aromatic modification at position 4 of the C-7 piperazinyl moiety.-KEY WORDS: antiviral agent, arylpiperazinyl fluoroquinolone, feline immunodeficiency virus (FIV), inhibitor of FIV replication.
The mode of action of R-91650, an arylpiperazinyl fluoroquinolone, on feline immunodeficiency virus (FIV) replication inhibitory activity was investigated. R-91650 inhibited replication of FIV at non-cytotoxic concentration levels in both acutely infected peripheral blood mononuclear cells and chronically infected P-CrFK cells. The compound reduced the intracellular p24 concentration levels in P-CrFK cells in a dose-dependent manner. Northern blot analysis revealed that R-91650 selectively prevented the accumulation of FIV mRNA in P-CrFK cells. However, the compound did not inhibit FIV-long terminal repeat (LTR) promoter activity in the reporter gene expression analysis. These data suggest that R-91650 is a novel inhibitor of FIV replication that inhibits a certain step or steps following transcription initiation of the FIV-LTR promoter.
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