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

• Strong binding of Schiff base derived 7-amino-coumarin compounds to albumin.
• Dihalogeno and nitro substitution: higher bioactivity and affinity to the protein.
• Site I binders proved by fluorescence quenching and docking studies.
• Significant role of the phenolate moiety in the binding event.

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.

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