Identification of a new class of low molecular weight antagonists against the chemokine receptor CXCR4 having the dipicolylamine-zinc(II) complex structure

J Med Chem. 2006 Jun 1;49(11):3412-5. doi: 10.1021/jm060025u.

Abstract

Several low molecular weight nonpeptide compounds having the dipicolylamine-zinc(II) complex structure were identified as potent and selective antagonists of the chemokine receptor CXCR4. These compounds showed strong inhibitory activity against CXCL12 binding to CXCR4, and the top compound exhibited significant anti-HIV activity. Zinc(II)-dipicolylamine unit-containing compounds proved to be useful and attractive lead compounds for chemotherapy of these diseases as nonpeptide CXCR4 antagonists possessing the novel scaffold structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology
  • Cricetinae
  • Cricetulus
  • HIV-1 / drug effects
  • Models, Molecular
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Picolines / chemical synthesis*
  • Picolines / chemistry
  • Picolines / pharmacology
  • Radioligand Assay
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Zinc*

Substances

  • Anti-HIV Agents
  • Chelating Agents
  • Organometallic Compounds
  • Picolines
  • Receptors, CXCR4
  • zinc(II) dipicolylamine
  • Zinc
  • Calcium