Synthesis, Characterization, and Biological Activity of a New Potent Class of Anti-HIV Agents, the Peroxoniobium-Substituted Heteropolytungstates

Kim, Gyu-Shik; Judd, Deborah A.; Hill, Craig L.; Schinazi, Raymond F.

doi:10.1021/jm00032a016

Cited by 74 publications

(37 citation statements)

References 6 publications

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“…Various POMs have been reported to interact with viral surface proteins and to inhibit the replication of several types of viruses [10][11][12][13][14]. Recent studies have shown that POMs have superior ability to selectively precipitate prion proteins, a property which could be useful in the development of immonoassays capable of detecting extremely low concentrations of infectious prions in blood and cerebrospinal fluid [15].…”

Section: Introductionmentioning

confidence: 99%

Structural characterization and reactivity of γ-octamolybdate functionalized by proline

Cartuyvels

Hecke

Meervelt

et al. 2008

Journal of Inorganic Biochemistry

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Section: Introductionmentioning

confidence: 99%

Structural characterization and reactivity of γ-octamolybdate functionalized by proline

Cartuyvels

Hecke

Meervelt

et al. 2008

Journal of Inorganic Biochemistry

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“…Several studies have indicated that certain paM are significantly inhibitory to human immunodeficiency virus (HIV) in vitro (Hill et al, 1990(Hill et al, , 1993Yamamoto et al, 1992;Inouye et al, 1993;Blasecki, 1994;Judd et al, 1994;Kim et al, 1994;Swart & Meijer, 1994;Moore etal., 1995;Shigeta et al, 1995). Herpesviruses have been reported to be inhibited by some of these compounds both in vitro (Fukuma et al, 1991;Yamamoto et al, 1992;Ikeda et al, 1993) and in vivo (Ikeda et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Influenza Virus-Inhibitory Effects of a Series of Germanium- and Silicon-Centred Polyoxometalates

Huffman

Sidwell

Barnard

et al. 1997

Antivir Chem Chemother

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A series of germanium- or silicon-centred heteropolytungstates (polyoxometalates) with the Barrel, Keggin or double Keggin structure were evaluated in vitro for their effects against influenza A (IV-A) and B (IV-B) viruses. Their 50% effective concentrations (EC50) against recent isolates of IV-A (H1N1) and IV-B ranged from 0.1 to 7.8 μM against IV-A (H3N2), the EC50 concentrations were often 10-fold higher. Recent clinical isolates of IV-A were generally more susceptible to these antiviral effects than older, laboratory-adapted strains. These experiments used inhibition of viral CPE in MDCK cells as determined microscopically and by Neutral Red (NR) uptake. Virus yield reduction studies indicated the 90% effective concentrations (EC90) ranged from 0.2 to 32 μM against these viruses. Cytotoxic or cell inhibitory concentrations (CC50), determined by NR uptake and total cell count, ranged from 38 to 189 μM, indicating high selective indices for some of these compounds. Altering time of addition of an active compound relative to infecting cells with IV-A (HINl) showed greatest efficacy when given early in viral replication. Five of the most active polyoxometalates were evaluated against IV-B infections in mice using intraperitoneal treatment beginning 4 h prior to virus exposure. Two of the compounds, one with the Barrel structure and the other with a double Keggin structure, were particularly inhibitory, preventing deaths, reducing arterial oxygen decline and lowering lung consolidation. Lung virus titres were reduced by a maximum of 0.7 log10. Therapy initiated 8 h post-virus exposure was not effective against this in vivo infection.

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“…W 601g 2-); (6) decatungstate (W1Q0324-), and (7) the Preyssler ion [(NaP 5W3 00114)14-j (Hill etal.199Ga,b) (Table 1). The potent and selective anti-human immunodeficiency virus type-1 (HIV-1) activity of polyoxometalates in infected human peripheral blood mononuclear (PBM) cells or cultured CD4+T-cell lines was reported by several workers (Hill et el., 199Ga,b;Yamamoto et al, 1992;Kim et al, 1994). Polyoxometalates also proved broadly inhibitory against retro-, myxo-, herpes-, toga-, rhabdoand arenavirus replication in vitro (Yamamoto et al, 1992;Ikeda et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

In vitro Antimyxovirus and Anti-Human Immunodeficiency Virus Activities of Polyoxometalates

Shigeta

Mori

Watanabe

et al. 1995

Antivir Chem Chemother

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Polyoxometalates have been shown to inhibit the replication of retro-, toga-, paramyxo- and herpesviruses. The primary mechanism of the anti-human immunodeficiency virus type 1 (HIV-1) action of polyoxometalates seems to be inhibition of binding of virus to cells and inhibition of syncytium formation. Since myxoviruses and HIV-1 are known to interact with the cytoplasmic membrane by adsorption and penetration of virus and by fusion of infected and uninfected cells, 25 polyoxometalates were examined for anti-ortho-, anti-paramyxovirus and anti-HIV-1 activity in vitro. Of the 25 compounds evaluated, 24 showed antiviral effects against influenza virus A, 11 showed activity against respiratory syncytial virus, six showed activity against measles virus, and 23 were considered effective against HIV-1 at a lower concentration than that producing cytotoxicity. Four polyoxotungstates which had potent inhibitory effects were examined for inhibitory effects against additional ortho- and paramyxoviruses, and proved to have a broad spectrum of antimyxoviral activity. HS-058, the Keggin sandwich compound K10Fe4(H2O)2(PW9O34)2·nH2O, was inhibitory against influenza viruses A and B, respiratory syncytial virus, measles virus, and parainfluenza virus 2, with median effective concentrations of 1.4, 21.8, 7.4, 0.8 and 0.32 μ,M, respectively. However, HS-058 had no effect on parainfluenza virus 3 or mumps virus. The median cytotoxic concentration of HS-058 for Madin-Darby canine kidney (MDCK) and HEp-2 cells was more than 200 μM and that for HMV-2 and Vero cells was about 50 μM. When HS-058 was added at different times after influenza A and respiratory syncytial virus infection, it inhibited binding of the latter but not of the former to cells. However, at higher concentrations, HS-054 and HS-058 inhibited haemolysis of chick erythrocytes by influenza virus and syncytium formation involving respiratory syncytial virus-infected cells and uninfected cells. Four times the median effective antiviral concentration of HS-058 completely inhibited the growth of influenza virus A in MDCK cells when compound was added before virus adsorption. Furthermore, when HS-058 was added after virus adsorption, it inhibited the yield of virus in MDCK cells infected at low but not at high multiplicity of infection.

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Synthesis, Characterization, and Biological Activity of a New Potent Class of Anti-HIV Agents, the Peroxoniobium-Substituted Heteropolytungstates

Cited by 74 publications

References 6 publications

Structural characterization and reactivity of γ-octamolybdate functionalized by proline

Structural characterization and reactivity of γ-octamolybdate functionalized by proline

Influenza Virus-Inhibitory Effects of a Series of Germanium- and Silicon-Centred Polyoxometalates

In vitro Antimyxovirus and Anti-Human Immunodeficiency Virus Activities of Polyoxometalates

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