Interaction mechanism of an antimalarial drug, sulfadoxine with human serum albumin

The main aim of this study was to characterize the molecular interaction between sulfadoxine and the major transport protein in the blood plasma, human serum albumin using fluorescence, absorption, circular dichroism, and voltammetric techniques along with computational methods. Sulfadoxine-induced changes in the fluorescence signal of human serum albumin hinted the complex formation between sulfadoxine and human serum albumin. Both values of the bimolecular quenching rate constant and UV-vis absorption spectral results characterized the quenching of human serum albumin fluorescence as static quenching. Analysis of the quenching results showed a moderate binding affinity of 3.39 × 10⁴ M⁻¹ at 300 K between sulfadoxine and human serum albumin. Thermodynamic data (entropy change = +104.42 J mol⁻¹ K⁻¹, enthalpy change = +5.25 kJ mol⁻¹) suggested the participation of hydrophobic interactions as the main binding force in the complex formation. Secondary and tertiary structural changes along with microenvironmental perturbation around protein fluorophores were also noticed upon sulfadoxine binding. The voltammetric spectral analysis further supported the complex formation between human serum albumin and sulfadoxine. Competitive ligand displacement results, as well as computational analysis, revealed binding of sulfadoxine to Sudlow’s Site I, located in subdomain IIA of human serum albumin.