Binding studies of potential amyloid-β inhibiting chalcone derivative with bovine serum albumin.

Chalcones (α-phenyl-β-benzoylethylene) and their natural-source derivatives have been investigated for their remarkable biological activities, like neuroprotective, anti-inflammatory, and anti-tumor properties. A triazole chalcone ligand (E)-3-(4-(dimethylamino)phenyl)-1-(4-((1-(2-(4-((E)-3-(4(dimethylamino)phenyl)acryloyl)phenoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)prop-2-en-1-one (L1) was synthesized by Cu(I)- catalysed click reaction. The mechanistic properties of L1 for therapy were evaluated by analyzing the binding interactions between L1 and bovine serum albumin (BSA) through photophysical and computational studies. The structural elucidation of ligand L1 was carried out by NMR and mass spectrometry. The Aβ inhibitory activity of L1 was studied by thioflavin T assay and transmission electron microscopy. The biomolecular interaction of L1 with bovine serum albumin was examined through multi-spectroscopic techniques in combination with in silico studies. UV-Visible absorption, fluorescence spectroscopy, circular dichroism, Förster resonance energy transfer, and three-dimensional fluorescence studies confirmed the formation of a BSA-L1 complex. The potential binding sites, mechanism of interactions, and variations in the environment of tyrosine and tryptophan amino acid residues of BSA were assessed at different temperatures. The binding constant for the Static quenching mechanism of intrinsic fluorescence of BSA was of the order of 10 M. The esterase enzyme activity assay in the presence of L1 revealed an increase in the protein enzyme activity. Molecular docking studies suggested L1 was predominantly bound to BSA by hydrogen bonds and Van der Waals forces.