Elucidating the interaction of letrozole with human serum albumin by combination of spectroscopic and molecular modeling techniques

Human serum albumin (HSA) is the most abundant protein found in human blood and is extensively employed in clinical applications such as hypovolemic shock treatment. Also, there has been a lot of attempt to use HSA as a carrier to deliver various drugs to their specific targets. Thus, clarify of structure, dynamics, functions, and features of HSA-drug complexes play an important role from the viewpoint of pharmaceutical and/or biochemical sciences. In this study, the interaction of letrozole, as a non-steroidal aromatase inhibitor, with HSA has been studied by combining different techniques such as UV-Vis, fluorescence spectroscopy, and computational methods. The binding of letrozole quenches the serum albumin fluorescence intensities. A clear decrease in fluorescence intensities of letrozole-HSA complex with the increase in temperature showed the static mode of fluorescence quenching. The results of Stern-Volmer procedure analysis showed that letrozole is bound only to a site from the HSA. The results of thermodynamic analysis showed that reaction between HSA and letrozole is spontaneous and exothermic. Furthermore, by monitoring the intrinsic fluorescence and using site markers competitive measurement, the binding of letrozole in the neighborhood of Sudlow's site I of HSA has been proved. Finally, computational methods substantiated the experimental findings and it was revealed that letrozole was bound to Arg-209, Trp-214, Ala-350, and Gly-238 residues of subdomain IIA and IIIA of HSA, respectively.