Abstract
Considering as a lead molecule the chemokine CXCR4 receptor antagonist AMD-3100, which shows significant anti-HIV activity in vitro and in vivo, we investigated a series of structurally related macrocyclic polyamines incorporating o,o'-phenanthroline or 2,2'-bipyridyl scaffolds as potential antiviral agents with lower toxicity and increased activity against both wild type X4-tropic and dual tropic HIV strains. The antiviral activity of these compounds was evaluated by susceptibility assays in PBMC (Peripheral Blood Mononuclear Cells) and compared to that of AMD-3100. The newly investigated compounds showed IC(50)s values in the low micromolar range and significantly inhibited the viral replication of wild type X4-tropic isolate and dual tropic strains. These macrocyclic polyamines constitute a promising class of HIV entry inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry*
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / pharmacology*
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Anti-HIV Agents / therapeutic use
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Benzylamines
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Cyclams
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Drug Resistance, Multiple*
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Drug Resistance, Viral*
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HIV Fusion Inhibitors / chemical synthesis
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HIV Fusion Inhibitors / chemistry*
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HIV Fusion Inhibitors / pharmacology*
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HIV Fusion Inhibitors / therapeutic use
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HIV Infections / drug therapy
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HIV-1 / drug effects*
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Heterocyclic Compounds / chemical synthesis
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Heterocyclic Compounds / chemistry
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Heterocyclic Compounds / pharmacology
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Heterocyclic Compounds / therapeutic use
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Humans
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Molecular Structure
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Phenotype
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Polyamines / chemical synthesis
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Polyamines / chemistry
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Polyamines / pharmacology
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Polyamines / therapeutic use
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Receptors, CXCR4 / antagonists & inhibitors
Substances
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Amines
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Anti-HIV Agents
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Benzylamines
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Cyclams
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HIV Fusion Inhibitors
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Heterocyclic Compounds
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Polyamines
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Receptors, CXCR4
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