CD4 mimics targeting the HIV entry mechanism and their hybrid molecules with a CXCR4 antagonist

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5853-8. doi: 10.1016/j.bmcl.2010.07.106. Epub 2010 Aug 3.

Abstract

Small molecules behaving as CD4 mimics were previously reported as HIV-1 entry inhibitors that block the gp120-CD4 interaction and induce a conformational change in gp120, exposing its co-receptor-binding site. A structure-activity relationship (SAR) study of a series of CD4 mimic analogs was conducted to investigate the contribution from the piperidine moiety of CD4 mimic 1 to anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. In addition, several hybrid molecules based on conjugation of a CD4 mimic analog with a selective CXCR4 antagonist were also synthesized and their utility evaluated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / metabolism
  • CD4 Antigens / chemistry
  • CD4 Antigens / metabolism
  • Cell Line
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / metabolism
  • HIV Fusion Inhibitors / chemical synthesis
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / toxicity
  • Humans
  • Piperidines / chemistry
  • Protein Binding
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / metabolism
  • Structure-Activity Relationship

Substances

  • CD4 Antigens
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors
  • Piperidines
  • Receptors, CXCR4
  • gp120 protein, Human immunodeficiency virus 1
  • piperidine