Publication

Abstract : Metformin hydrochloride is an oral hypoglycemic agent prescribed for the treatment of diabetes mellitus type II. Three fluorinated metformin derivatives (MTF1, MTF2 and MTF3) were synthesized and investigated for their human bloodstream – human serum albumin (HSA) interaction studies by multi-spectroscopic techniques (circular dichroism, steady state, time-resolved and synchronous fluorescence), combined with molecular docking and quantum chemical calculation. Steady state and time-resolved fluorescence indicate static fluorescence quenching as the main mechanism. Binding of HSA/metformin is moderate and there is just one main binding site in the protein structure for all samples. In addition, MTF1 can cause weak perturbations on the secondary structure of the albumin, while MTF2 and MTF3 cause moderate perturbations. Synchronous fluorescence spectroscopy showed that MTF1 and MTF3 can decrease the hydrophobicity around the Trp-214 amino acid residue. Molecular docking results suggest hydrogen bonding, van der Waals and hydrophobic interactions as the main binding forces for the association HSA:MTF1 and HSA:MTF2, while for HSA:MTF3 the main binding forces are hydrogen bonding and van der Waals interaction.