Synthesis and in Vitro Screening of New Series of 2,6-Dipeptidyl-anthraquinones: Influence of Side Chain Length on HIV-1 Nucleocapsid Inhibitors

J Med Chem. 2016 Mar 10;59(5):1914-24. doi: 10.1021/acs.jmedchem.5b01494. Epub 2016 Feb 3.

Abstract

2,6-Dipeptidyl-anthraquinones are a promising class of nucleic acid-binding compounds that act as NC inhibitors in vitro. We designed, synthesized, and tested new series of 2,6-disubstituted-anthraquinones, which are able to bind viral nucleic acid substrates of NC. We demonstrate here that these novel derivatives interact preferentially with noncanonical structures of TAR and cTAR, stabilize their dynamics, and interfere with NC chaperone activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemical synthesis
  • Alanine / chemistry
  • Alanine / pharmacology
  • Anthraquinones / chemical synthesis
  • Anthraquinones / chemistry
  • Anthraquinones / pharmacology*
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Binding Sites / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / chemistry
  • Glycine / pharmacology
  • HIV-1 / chemistry
  • HIV-1 / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nucleocapsid / antagonists & inhibitors*
  • Nucleocapsid / metabolism
  • Response Elements / drug effects
  • Structure-Activity Relationship

Substances

  • Anthraquinones
  • Anti-HIV Agents
  • Alanine
  • Glycine