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 (K D ~ 0.03-2.09 M).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 proteinligand 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.

Interaction of Small Zinc Complexes with Globular Proteins and Free Tryptophan

“…However, the correction is really not necessary if the absorbance of the complex is less than 0.02, which is the case for Complex 6 over the range of concentrations used in this study [58]. For Complexes 3 and 4, the absorbance exceeds 0.02 and the observed fluorescence, obs , was corrected for the inner-filter effect using the following equation [34,59]:…”

Drug likeness prediction of 5-hydroxy-substituted coumarins with high affinity to 5-HT1A and 5-HT2A receptors

“…In recent years, various research groups have been involved in the examinations of conformational changes of HSA, joined with the interaction between protein and biologically active natural and synthetic compounds such as coumarin and its analogues (Dömötör et al, 2014;Garg et al, 2013;Gokara et al, 2010;Yeggoni et al, 2014). The potency of coumarins may be modified by the number of small substituents, such as the hydroxy, alkoxy or carbonyl groups in various positions of coumarin moiety (Abdelhafez et al, 2010;Drzewiecka et al, 2013;Hassan et al, 2016;Paul et al, 2013;Sarkanj et al, 2013;Tsay et al, 2013).…”

Comparative studies on the human serum albumin binding of the clinically approved EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the investigational inhibitor KP2187

“…The binding of the protonated (HL + ) and charge neutral (L 0 ) forms of GEF and KP2187 to certain sites was studied in the next step. The drug binding site I of HSA is described as a continuous non-polar cavity with three hydrophobic sub-chambers and two polar patches fairly large, structurally resilient pocket was shown to bind ligands of various size and structure [12,33] and even compounds which have similar chemical structure could bind to this site in different relative orientations [43]. The pocket is positively charged; therefore interactions with anionic or partially negative moieties of ligands are favoured for binding.…”