Biophysical and Computational Analysis of a Potent Antimalarial Compound Binding to Human Serum Albumin: Insights for Drug–Protein Interaction

We aimed to investigate the interaction mechanism of transport protein Human serum albumin (HSA) with a synthesized compound, QP-11, with tested antimalarial properties to monitor the changes in the protein because of QP-11 binding. The interaction between the antimalarial compound QP-11 and HSA was thoroughly investigated through a multidimensional approach, utilizing UV-VIS spectroscopy, fluorescence, time-resolved fluorescence, and CD (Circular dichroism), alongside molecular docking techniques. Our findings unveiled a robust 1:1 binding pattern, signifying a strong affinity between QP-11 and HSA. Employing static quenching, evidenced by time-resolved fluorescence spectroscopy, QP-11 was observed to induce fluorescence quenching of HSA, particularly binding to subdomain IIA. Thermodynamic parameters indicated that van der Waals forces and hydrogen bonding predominantly facilitated the binding, with increased temperature compromising complex stability. The 3D fluorescence and CD results demonstrated QP-11-induced conformational changes in HSA. Both experimental and in silico analyses suggested a spontaneous, exothermic binding reaction. The profound impact of the QP-11–HSA interaction underscores the potential for QP-11 in antimalarial drug development, encouraging further exploration for dose design and enhanced pharmacodynamic and pharmacokinetic properties.