A New Fluoroquinolone Derivative Exhibits Inhibitory Activity against Human Immunodeficiency Virus Type 1 Replication

Abstract

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.

8-Difluoromethoxy-4-Quinolone Derivatives as Anti-Feline Immunodeficiency Virus (FIV) Agents: Important Structural Features for Inhibitory Activity of FIV Replication

“…However, we failed to reproduce their results in our assay system [19]. Through the screening of our chemical library and a derivatization study, we found some arylpiperazinyl fluoroquinolones that inhibit HIV-1 replication both in acutely and in chronically HIV-1-infected cells [12,19,20]. These results were confirmed by another group [3].…”

“…Nozaki-Renard et al reported that some anti-bacterial fluoroquinolones protected human lymphocyte cell lines from HIV-1-induced cytopathicity [25,26]. However, we failed to reproduce their results in our assay system [19]. Through the screening of our chemical library and a derivatization study, we found some arylpiperazinyl fluoroquinolones that inhibit HIV-1 replication both in acutely and in chronically HIV-1-infected cells [12,19,20].…”

New Anti-Human Immunodeficiency Virus Type 1 6-Aminoquinolones: Mechanism of Action

“…Our results therefore suggest that WM5 may effectively sequester TAR RNA affecting HIV-1 transcription. Fluoroquinolone derivatives have recently been shown to be potent and selective inhibitors of HIV-1 replication (5,22,29,36,55). A representative compound of the series, K12, has been reported to inhibit HIV-1 transcription, reducing the synthesis of HIV-1 mRNA in chronically infected cells without significantly affecting Tat activity (5).…”

“…Quinolone derivatives have been shown to inhibit HIV-1 replication in de novo-and chronically infected cells (4,5,22,29,(35)(36)(37)55). A new fluoroquinolone, K12, bearing an omethoxyphenyl-piperazinyl group and a difluoromethoxyl group at positions 7 and 8, respectively, was reported to have strong and selective anti-HIV-1 activity (4).…”

Inhibition of Human Immunodeficiency Virus Type 1 Tat- trans -Activation-Responsive Region Interaction by an Antiviral Quinolone Derivative

“…Quinolone derivatives have been shown to inhibit HIV-1 replication in acutely and chronically infected cells (1, 2, 14,22,[24][25][26]36). Recently, our group developed a new class of 6-substituted quinolones and tested their antibacterial and anti-HIV-1 activities (6,30).…”