Polysulfated sialic acid derivatives as anti-human immunodeficiency virus

Biomed Pharmacother. 2005 Sep;59(8):423-9. doi: 10.1016/j.biopha.2005.07.005.

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.

Publication types

  • Comparative Study

MeSH terms

  • Alkylation
  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / toxicity
  • Anticoagulants / administration & dosage
  • Anticoagulants / pharmacology
  • Dextran Sulfate / pharmacology
  • Dose-Response Relationship, Drug
  • HIV Core Protein p24 / metabolism
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects*
  • Humans
  • Inhibitory Concentration 50
  • Lethal Dose 50
  • Lipids / chemical synthesis
  • Lipids / pharmacology*
  • Lipids / toxicity
  • Macaca fascicularis
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Animal
  • N-Acetylneuraminic Acid / analogs & derivatives*
  • N-Acetylneuraminic Acid / chemical synthesis
  • N-Acetylneuraminic Acid / pharmacology
  • N-Acetylneuraminic Acid / toxicity
  • Sialic Acids / chemical synthesis
  • Sialic Acids / pharmacology*
  • Sialic Acids / toxicity
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • U937 Cells
  • Virus Replication / drug effects
  • Zidovudine / pharmacology

Substances

  • (2,2-bis(docosyloxymethyl)propyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium oxysulfonyl)glycero-alpha-galacto-2-nonulopyranosid)onate
  • Anti-HIV Agents
  • Anticoagulants
  • HIV Core Protein p24
  • Lipids
  • Sialic Acids
  • Zidovudine
  • Dextran Sulfate
  • N-Acetylneuraminic Acid