Human Serum Albumin Binding with Cotarnine Derivatives and Its Hemostatic, Wound-Healing, and Antibacterial...

Human serum albumin (HSA) plays a key role in regulating the transport and bioavailability of therapeutic molecules, making protein-ligand interaction studies essential for assessing biomedical compatibility. In this work, the interaction of cotarnine and its derivatives with HSA was systematically investigated using spectroscopic, thermodynamic, and molecular docking approaches, along with evaluation of antibacterial, wound healing, and hemostatic activities. Spectroscopic analyses confirmed efficient binding of the derivatives to HSA without disrupting its native secondary structure, while thermodynamic studies revealed spontaneous, enthalpy-driven interactions dominated by noncovalent forces. Docking studies identified favorable binding orientations within HSA binding pockets, complementing the experimental results. All derivatives of cotarnine show greater binding and biological activity, such as wound healing and hemostatic, than cotarnine. Among the derivatives, L2 exhibited the strongest binding affinity and superior biological performance, which can be attributed to enhanced hydrophobic interactions arising from its chloro-substituted aromatic moiety. Overall, the combined biophysical, computational, and biological findings highlight cotarnine derivatives, particularly L2, as promising multifunctional candidates for wound-healing and related biomedical applications.