Unveiling the binding interactions of selected antimalarial drugs with major plasma transporter

Title : Unveiling the binding interactions of selected antimalarial drugs with major plasma transporter

Abstract:

Using a variety of spectroscopic methods and in silico analysis, the binding interactions between three antimalarial medications, mefloquine (MEF), lumefantrine (LUM), and pyrimethamine (PYR) and the primary plasma transporter, human serum albumin (HSA) were examined. Molecular docking analysis designated Sudlow’s Site I, located in subdomain IIA of HSA, as the preferred binding site of these drugs, which was also supported by competitive drug displacement results. The quenching of protein (HSA) fluorescence induced by these drugs was characterized as static quenching, thus suggesting drug-HSA complex formation. This was also supported by UV-Vis absorption spectral results. Moderate binding affinity between these drugs and HSA was revealed from the association constant, K_a values (1.32-7.27 ´ 10⁴ M^-1). Both molecular docking results and thermodynamic data predicted noncovalent forces, viz., hydrogen bonds, hydrophobic and van der Waals forces, to stabilize drug-HSA complexes. Smaller modifications to secondary and tertiary structures as well as microenvironmental alterations surrounding protein fluorophores were also brought about by drug binding.

Audience Take Away Notes:

• The audience will learn about the characteristics of antimalarial drug-HSA interaction
• It will reflect the efficacy of these drugs in the presence of other drugs, which bind to the same site on HSA
• Drug-drug interactions can be studied using the binding characteristics of antimalarial drugs

Biography:

Dr. Saad Tayyab studied Biochemistry at Aligarh Muslim University, India, completing Masters and Ph.D. degrees in 1981 and 1987, respectively. He is currently working as a Professor of Pharmaceutical Chemistry at UCSI University, Kuala Lumpur, Malaysia. Before joining UCSI University, Dr. Saad served at Universiti Malaya (2004-2018), Haramaya University, Ethiopia (2001-2004), Aligarh Muslim University, India (1988-2001), and the University of Kashmir, India (1987-1988). He was admitted as a Fellow, Royal Society of Chemistry, UK, in 2017, Fellow, Royal Society of Biology, UK, in 2019, Member, American Chemical Society in 2020, and Member, Sigma Xi in 2024. He is serving as an Editorial Board member for several journals. He has published over 150 journal papers, 17 popular articles, 1 book, 2 book chapters, and 1 learning aid. Several research students (16 Ph.D., 6 M.Phil., 1 M.D., and 13 M.Sc.) completed their degrees under his supervision, and he guided 32 undergraduate projects. His research interests include drug-protein interaction, protein folding, protein/enzyme stability, and protein structure-function. He possesses an h-index of 27, and his name is included in the reviewers’ lists of many international journals.