Combinations of isoprinosine and 3'-azido-3'-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1

Schinazi, Raymond F.; Cannon, Deborah; Arnold, Barbara H.; Martino-Saltzman, David

doi:10.1128/aac.32.12.1784

Cited by 44 publications

(37 citation statements)

References 19 publications

(14 reference statements)

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“…HIV-1 (strain LAV-1) was obtained from the Centers for Disease Control, Atlanta, Ga., and propagated in phytohemagglutinin-stimulated human PBM cells as described previously (33). The details of the methods used for infection and assaying the anti-HIV-1 effect in infected human PBM cells have been reported previously (33).…”

mentioning

confidence: 99%

“…PBM cells from healthy HIV-1-and hepatitis B virus-seronegative donors were isolated and propagated as described previously (33). HIV-1 (strain LAV-1) was obtained from the Centers for Disease Control, Atlanta, Ga., and propagated in phytohemagglutinin-stimulated human PBM cells as described previously (33).…”

mentioning

confidence: 99%

“…The RT assays were performed at 37°C in 96-well microdilution plates by methods described previously (33,36). The results were expressed as disintegrations per minute per milliliter of the originally clarified supernatant.…”

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confidence: 99%

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Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro

Eriksson

Schinazi

1989

Antimicrob Agents Chemother

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Combinations of 3'-azido-3'-deoxythymidine and phosphonoformate produced a moderate synergistic inhibitory effect against human immunodeficiency virus type 1 in vitro at concentrations that are easily achieved in humans. The synergistic effect was more pronounced with increasing concentrations and was not secondary to toxic effects of the drugs. 3'-Azido-3'-deoxythymidine neither inhibited the replication of human cytomegalovirus in human embryonic lung fibroblasts nor interfered with the anticytomegalovirus effect of phosphonoformate. By using partially purified reverse transcriptase of human immunodeficiency virus type 1 and human cytomegalovirus DNA polymerase, various combinations of 3'-azido-3'-deoxythymidine-5'-triphosphate and phosphonoformate produced strong indications of additive interactions. The synergistic interactions in infected cells and the additive effects observed at the reverse transcriptase level indicate that mechanisms other than the reverse transcriptase may be of importance for the inhibition of human immunodeficiency virus replication by these two compounds. A concomitant treatment of cytomegalovirus infections, such as cytomegalovirus retinitis, with phosphonoformate in patients with acquired immunodeficiency syndrome receiving 3'-azido-3'-deoxythymidine may be appropriate, and this combination may also be useful in controlling human immunodeficiency virus infection.

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Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro

Eriksson

Schinazi

1989

Antimicrob Agents Chemother

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“…The RT results were expressed in disintegrations per minute per milliliter of originally clarified supernatant. 25 The compounds were evaluated for their potential toxic effects on uninfected phytohemagglutinin-stimulated human PBMCs and also in CEM and Vero cells. PBMCs were obtained from whole blood of healthy HIV-1 and hepatitis B virus-seronegative volunteers and collected by single-step Ficoll-Hypaque discontinuous gradient centrifugation.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel 2'-Spirocyclopropanoid 4'-Deoxythreosyl Phosphonic Acid Nucleoside Analogues

Shen¹,

Hong

2013

Bulletin of the Korean Chemical Society

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Efficient synthetic route to novel 2'-spirocyclopropanoid 4'-deoxythreosyl phosphonic acid nucleosides was described from 1,4-dihydroxy-2-butene. Cyclopropane moiety was prepared via ester enolate alkylation using (2-chloroethyl)dimethylsulfonium iodide. Synthesized nucleoside analogues 16, 19, 23 and 26 were tested for anti-HIV activity as well as cytotoxicity. However, none of them showed any anti-HIV activity or cytotoxicity up to 100 µM.

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“…human peripheral blood mononuclear cells (PBMCs) have been published previously (Schinazi et al, 1988(Schinazi et al, , 1990 (Belen'kii & Schinazi, 1994 (Model EL 312e;Inc.,Winooski,VT,USA). The 50% inhibition concentration (IC 50 ) was determined from the concentration-response curve using the median effect method (Stuyver et al, 2002;Belen'kii & Schinazi, 1994).…”

Section: Antiviral Assays the Procedures For The Antiviral Assays Inmentioning

confidence: 99%

PAMAM Dendrimers and Branched Polyethyleneglycol (Nanoparticles) Prodrugs of (-)-β-D-(2R, 4R)-dioxolane-thymine (DOT) and Their Anti-HIV Activity

Liang

Janarthanan

Rapp

et al. 2006

Antivir Chem Chemother

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The synthesis, characterization, anti-HIV activity and cytotoxicity of dendrimers of (-)-β β-D-(2R,4R)-dioxolane-thymine (DOT) and polyethylene glycol (PEG)-DOT conjugates are described. Dendrimers in this study were polyamidoamine (PAMAM) generation 2.0, 3.0, 5.0 and 6.0, along with 8.0-branched PEG with a molecular weight of 40 kDa. DOT was attached to PAMAM dendrimers or branched PEG via ester or phosphate groups. Size exclusion chromatography was used to purify the dendrimers and PEG conjugates, which were characterized by NMR and MALDI-TOF mass spectrometry. The synthesized PAMAM dendrimers and PEG conjugates were evaluated for anti-HIV activity against HIV-1 LAI in primary human peripheral blood mononuclear cells (PBMCs) and cytotoxicity in PBMCs, CEM and Vero cells. PAMAM dendrimers of DOT with ester linkages and particularly phosphate linkers showed an increase in anti-HIV potency in comparison with DOT alone (140-and 56-fold, respectively). Unfortunately, the PAMAM dendrimers also exhibited increased cytotoxicity. Anti-HIV activity of PEG-DOT conjugates was found to be lower than that of DOT.

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Combinations of isoprinosine and 3'-azido-3'-deoxythymidine in lymphocytes infected with human immunodeficiency virus type 1

Abstract: Since clinical trials are being planned with the immunomodulating drug isoprinosine combined with the antiviral drug 3'-azido-3'-deoxythymidine (AZT) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex,

Cited by 44 publications

References 19 publications

Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro

Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro

Synthesis of Novel 2'-Spirocyclopropanoid 4'-Deoxythreosyl Phosphonic Acid Nucleoside Analogues

PAMAM Dendrimers and Branched Polyethyleneglycol (Nanoparticles) Prodrugs of (-)-β-D-(2R, 4R)-dioxolane-thymine (DOT) and Their Anti-HIV Activity

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