Abstract
We report the synthesis of a novel alkyl polysulfated sialic acid derivative denoted as NMSO3. NMSO3 exhibited potent inhibition against both laboratory and clinical human immunodeficiency virus type 1 (HIV-1). The anti-viral activity of this compound (1 uM) was compared to dextran sulfate (3 uM), and was found to be more potent against HIV-1IIIb than AZT (10 uM). The anti-coagulation time was more than 15-fold shorter than that of dextran sulfate. An in vivo anti-viral study of NMSO3 in NOD-SCID-PBL mice HIV model showed complete protection of the animals from virus challenge at the concentration of 10 mg/kg. This suggests that NMSO3 can be effective in the treatment of HIV-infected individuals.
MeSH terms
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Alkylation
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Animals
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / pharmacology*
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Anti-HIV Agents / toxicity
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Anticoagulants / administration & dosage
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Anticoagulants / pharmacology
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Dextran Sulfate / pharmacology
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Dose-Response Relationship, Drug
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HIV Core Protein p24 / metabolism
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HIV Infections / prevention & control*
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HIV-1 / drug effects*
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Humans
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Inhibitory Concentration 50
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Lethal Dose 50
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Lipids / chemical synthesis
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Lipids / pharmacology*
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Lipids / toxicity
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Macaca fascicularis
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Models, Animal
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N-Acetylneuraminic Acid / analogs & derivatives*
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N-Acetylneuraminic Acid / chemical synthesis
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N-Acetylneuraminic Acid / pharmacology
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N-Acetylneuraminic Acid / toxicity
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Sialic Acids / chemical synthesis
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Sialic Acids / pharmacology*
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Sialic Acids / toxicity
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T-Lymphocytes / drug effects
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T-Lymphocytes / metabolism
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T-Lymphocytes / virology
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U937 Cells
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Virus Replication / drug effects
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Zidovudine / pharmacology
Substances
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(2,2-bis(docosyloxymethyl)propyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium oxysulfonyl)glycero-alpha-galacto-2-nonulopyranosid)onate
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Anti-HIV Agents
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Anticoagulants
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HIV Core Protein p24
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Lipids
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Sialic Acids
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Zidovudine
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Dextran Sulfate
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N-Acetylneuraminic Acid