title: Differential interactions of the broad spectrum drugs artemisinin, dihydroartemisinin and artesunate with serum albumin.
abstract: Artemisinin is a drug, widely used in malaria treatment. As the binding affinity of artemisinin and its derivatives dihydroartemisinin and artesunate to blood serum proteins might influence the effectiveness of the drug, binding of artemisinin and derivatives to serum albumin was studied under near physiological conditions. Binding kinetics indicate a simple, single-step association process for all artemisinin derivatives. The determined changes in enthalpy and entropy upon drug binding clearly indicate that hydrophobic forces are most important for artemisinin and dihydroartemisinin binding, whereas binding of artesunate is governed by both hydrophilic and hydrophobic forces. Key residues, which are most likely involved in binding of the respective compounds, were identified in subsequent protein/drug docking studies. The obtained results not only explain differences in between artemisinin and derivatives but generally illustrate how slight modifications in a drug can significantly affect principles underlying drug binding to target proteins.
authors.affiliation: Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany. anbazhagan@scbt.sastra.edu
authors.forename: Anbazhagan
authors.initials: A
authors.lastname: Veerappan
authors.forename: Tolga
authors.initials: T
authors.lastname: Eichhorn
authors.forename: Maen
authors.initials: M
authors.lastname: Zeino
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.forename: Dirk
authors.initials: D
authors.lastname: Schneider
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077332:Artesunate; D002417:Cattle; D004359:Drug Therapy, Combination; D057927:Hydrophobic and Hydrophilic Interactions; D008288:Malaria / Q000188:drug therapy; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D037621:Artemisinins; D012709:Serum Albumin; D000077332:Artesunate; C039060:artenimol; C031327:artemisinin
keywords: Antimalaria agent; Artemisinin; Artesunate; BSA; Serum protein