Binding Behavior of Anticancer Agent Trametinib Across Different Mammalian Serum Albumins: A Comparative Perspective

Türkçe

Understanding the binding interactions between drugs and serum albumins is crucial for evaluating pharmacokinetics, bioavailability, and species-specific therapeutic responses. In this study, the binding behavior of the anticancer agent trametinib (TMB) using serum albumins derived from four distinct mammals, namely—human (HSA), bovine (BSA), goat (GSA), and sheep (SSA)—was investigated using steady-state fluorescence spectroscopy. TMB caused a concentration-dependent quenching of intrinsic albumin fluorescence, indicating complex formation. Analysis of Stern–Volmer and double logarithmic plots revealed that the quenching mechanism was predominantly static in nature, as supported by high bimolecular quenching rate constants (kq ~1012 M-1 s-1), which exceeded the diffusion-controlled limit. Binding parameters, including the association constant (Ka) and binding stoichiometry (n), were calculated, with all albumins exhibiting a 1:1 binding ratio. Among the studied proteins, BSA displayed the strongest affinity for TMB, followed by GSA, HSA, and SSA. Thermodynamic evaluation via Gibbs free energy change (ΔG) confirmed the spontaneity of the interaction, with ΔG values ranging from −25.2 to −28.9 kJ mol-1. These results not only provide molecular-level insight into TMB–albumin interactions but also support the rational selection of animal models in preclinical pharmacological studies based on their albumin binding profiles.