Anti-HIV-1 activity of a tripodal receptor that recognizes mannose oligomers

Eur J Med Chem. 2015 Dec 1:106:132-43. doi: 10.1016/j.ejmech.2015.10.027. Epub 2015 Oct 21.

Abstract

The glycoprotein gp120 of the HIV-1 viral envelope has a high content in mannose residues, particularly α-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5-triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes α-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1.

Keywords: AIDS; Antiviral agents; HIV; Integrase; Polyphenols.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • HIV Envelope Protein gp120 / antagonists & inhibitors*
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / enzymology*
  • HIV-1 / metabolism
  • Mannans / chemical synthesis
  • Mannans / chemistry
  • Mannans / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • HIV Envelope Protein gp120
  • HIV Integrase Inhibitors
  • Mannans
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1