Exploring the combination characteristics of lumefantrine, an antimalarial drug and human serum albumin through spectroscopic and molecular docking studies

• Main Authors: Musa, Kabiru Abubakar, Ridzwan, Nor Farrah Wahidah, Mohamad, Saharuddin B., Tayyab, Saad
• Format: Article
• Published: Taylor & Francis 2021
• Subjects: QH301 Biology
• Online Access: http://eprints.um.edu.my/26504/

Binding of lumefantrine (LUM), an antimalarial drug to human serum albumin (HSA), the main carrier protein in human blood circulation was investigated using fluorescence quenching titration, UV-vis absorption and circular dichroism (CD) spectroscopy as well as molecular docking. LUM-induced quenching of the protein (HSA) fluorescence was characterized as static quenching, as revealed by the decrease in the value of the Stern-Volmer quenching constant, K-sv with increasing temperature, thus suggesting LUM-HSA complex formation. This was also confirmed from the UV-vis absorption spectral results. Values of the association constant, K-a for LUM-HSA interaction were found to be within the range, 7.27-5.01 x 10(4) M-1 at three different temperatures, i.e. 288 K, 298 K and 308 K, which indicated moderate binding affinity between LUM and HSA. The LUM-HSA complex was stabilized by hydrophobic interactions, H-bonds, as well as van der Waals forces, as predicted from the thermodynamic data (Delta S = +50.34 J mol(-1) K-1 and Delta H = -12.3 kJ mol(-1)) of the binding reaction. Far-UV and near-UV CD spectral results demonstrated smaller changes in both secondary and tertiary structures of HSA upon LUM binding, while three-dimensional fluorescence spectra suggested alterations in the microenvironment around protein fluorophores (Trp and Tyr). LUM binding to HSA offered stability to the protein against thermal stress. Competitive drug displacement results designated Sudlow's Site I, located in subdomain IIA of HSA as the preferred binding site of LUM on HSA, which was well supported by molecular docking analysis.