title: Interaction of anticancer reduced Schiff base coumarin derivatives with human serum albumin investigated by fluorescence quenching and molecular modeling.
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.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Dömötör
authors.affiliation: Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.affiliation: Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
authors.forename: Darius
authors.initials: D
authors.lastname: Karcz
authors.affiliation: Department of Science, Institute of Technology Tallaght, Dublin 24, Ireland.
authors.forename: Maureen
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Department of Science, Institute of Technology Tallaght, Dublin 24, Ireland.
authors.forename: Bernadette S
authors.initials: BS
authors.lastname: Creaven
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary; HAS-USZ Bioinorganic Chemistry Research Group, Dóm tér 7, H-6720 Szeged, Hungary. Electronic address: enyedy@chem.u-szeged.hu.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Enyedy
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D003374:Coumarins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011522:Protons; D012545:Schiff Bases / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D011522:Protons; D012545:Schiff Bases; D012709:Serum Albumin; C030123:coumarin
keywords: 7-Amino-coumarin; Dissociation constants; Docking; Fluorometry; Human serum albumin