Synthesis and Anti-HIV Activity of a Novel Series of Isoquinoline-Based CXCR4 Antagonists

Molecules. 2021 Oct 18;26(20):6297. doi: 10.3390/molecules26206297.

Abstract

An expansion of the structure-activity relationship study of CXCR4 antagonists led to the synthesis of a series of isoquinolines, bearing a tetrahydroquinoline or a 3-methylpyridinyl moiety as head group. All compounds were investigated for CXCR4 affinity and antagonism in competition binding and calcium mobilization assays, respectively. In addition, the anti-HIV activity of all analogues was determined. All compounds showed excellent activity, with compound 24c being the most promising one, since it displayed consistently low nanomolar activity in the various assays.

Keywords: CXCR4 antagonist; HIV; isoquinoline.

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Drug Design
  • HIV / drug effects*
  • HIV / isolation & purification
  • HIV / pathogenicity
  • HIV Infections / drug therapy*
  • HIV Infections / pathology
  • HIV Infections / virology
  • Humans
  • Isoquinolines / chemistry*
  • Molecular Structure
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • CXCR4 protein, human
  • Isoquinolines
  • Receptors, CXCR4