Experimental and Computational Studies of ND-Drived Schiff base ligands with HSA; Molecular Dynamics Simulation, QSAR Modeling and Molecular Docking Studies

Human Serum Albumin (HSA) is a negatively charged, is present in high concentration in plasma. Existenceof several binding sites and an extraordinary binding capacity with a high degree of conformational flexibilitymakes HSA a versatile carrier to transport a variety of endogenous and exogenous ligands including drugmolecule. Herein, twelve Schiff-base ligands (L۱-L۱۲) have been synthesised by the reaction of ۱,۵-naphthalenediamine (ND) with four aldehyde drivatives and characterised by different spectroscopictechniques. The interaction of these ligands with HSA was investigated under pseudo-physiologicalconditions by fluorescence and circular dichroism (CD). The fluorescence quenching of HSA at ۳۴۳ nm uponaddition of the L۱-L۱۲, reveals the formation of complexes between Schiff-bases and HSA. The magnitudeof the Kq values for L۱-L۱۲ ligands (greater than ۲.۰ × ۱۰۱۰ M−۱ s−۱) confirm the static mechanism forquenching. Furthermore, the CD spectra show that the random coil and antiparallel parts of the secondarystructure have trends inverse to the helix part in the presence of Schiff base ligands. The optimization of thestructures was performed by using DFT/B۳LYP method with the ۶–۳۱۱++G(d,p) basis set. Finally, themolecular docking studies with AutoDocVina software and molecular dynamics simulations using Gromacspackage were applied to estimate the binding affinity between HSA and L۱-L۱۲ ligands. The results showthe strong intreraction between the protein and the ligands with the binding affinities in the range of -۷.۲ ─ -۱۱.۱ kcal/mol. The diffrences of the binding constants for the interaction of L۱-L۱۲ with HSA was realizedby QSAR toolbox.