In Vitro Study of the Interaction Between HSA and 4-Bromoindolylchalcone, a Potent Human MAO-B Inhibitor: Spectroscopic and Molecular Modeling Studies

Based on our previous report, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9) showed potent and reversible hMAO-B inhibitor with K-i=0.010 +/- 0.005 mu M and a selectivity index of 120 - better than selegiline, the standard drug for hMAO-B. To continue the pharmacological investigation of IC9, the present study describes in vitro interaction between the titled compound and human serum albumin (HSA) under physiological condition by spectroscopic techniques (UV-Vis, circular dichroism, steady-state, synchronous, 3D and time-resolved fluorescence) combined with molecular docking and quantum chemical calculations. There is a moderate ground-state association between HSA:IC9, which is enthalpically and entropically driven. This association occurs mainly inside Sudlow's site I. There is a weak perturbation on the secondary structure and on the microenvironment around Trp residue as evidenced by circular dichroism and synchronous fluorescence. Molecular docking suggested that IC9 can interact via hydrogen bonding, hydrophobic and electrostatic forces, whereas quantum chemical calculations suggested that the presence of a bromine atom is supporting the ability of binding between IC9 and HSA through an electrostatic interaction.