Interaction of anticancer reduced Schiff base coumarin derivatives with human serum albumin investigated by fluorescence quenching and molecular modeling

Orsolya Dömötör, Tiziano Tuccinardi, Darius Karcz, Maureen Walsh, Bernadette S. Creaven, Éva A. Enyedy

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The specific binding of five reduced Schiff base derived 7-amino-coumarin compounds with antitumor activity to human serum albumin, the principal binding protein of blood, was studied by fluorescence spectroscopy. Their conditional binding constants were computed and the reversible binding at the Sudlow's site I was found to be strong (KD ∼ 0.03-2.09 μM). Based on the data albumin can provide a depot for the compounds and is responsible for their biodistribution and transport processes. The experimental data is complemented by protein-ligand docking calculations for two representatives which support the observations. The proton dissociation constants of the compounds were also determined by UV-Vis spectrophotometric and fluorometric titrations to obtain the actual charges and distribution of the species in the various protonation states at physiological pH.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalBioorganic Chemistry
Volume52
DOIs
Publication statusPublished - Jan 1 2014

    Fingerprint

Keywords

  • 7-Amino-coumarin
  • Dissociation constants
  • Docking
  • Fluorometry
  • Human serum albumin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this