Elucidation of the interaction between human serum albumin (HSA) and 3,4-methylenedioxyde-6-iodo-benzaldehyde-thiosemicarbazone, a potential drug for Leishmania amazonensis: Multiple spectroscopic and dynamics simulation approach

The interaction between human serum albumin (HSA), the most abundant protein in the human circulatory system, and the potential anti-parasitic drug (E)-2-((6-iodobenzo[d][1,3]dioxol-5-yl)methylene)hydrazinecarbothioamide (6-IPTSC) was evaluated in vitro by spectroscopic techniques (circular dichroism, steady-state, time-resolved and synchronous fluorescence) combined with molecular docking and dynamics simulation. The interaction HSA:6-IPTSC can occur via a static process, which involves a ground-state association. The molecule 6-IPTSC binds moderately (Kb ~ 104 M−1) and spontaneously (ΔG° < 0) with HSA. The experimental thermodynamic values ΔH° < 0 and ΔS° > 0 resulted in negative values for ΔG° at 296, 303 and 310 K, indicating that the binding HSA:6-IPTSC is entropically and enthalpically driven. There is just one binding site in HSA for 6-IPTSC, namely Sudlow's site I. The binding process does not perturb significantly the secondary structure of the protein, as well as the microenvironment around the Tyr residue. Molecular docking results suggest that inside Sudlow's site I the potential anti-parasitic drug can interact with Lys(K)-197, Trp(W)-213, Gln(Q)-219, Arg(R)-220, Glu(E)-448, and Ser(S)-453 residues via hydrogen bonding and hydrophobic forces. Overall, the dynamics simulation results complemented the molecular docking discussion, mainly showing that Gln(Q)-219, Arg(R)-220, and Glu(E)-448 residues are not the primary amino acids involving in the binding ability HSA:6-IPTSC. Besides, these results confirm that 6-IPTSC does not perturb the secondary structure of the protein significantly.