Characterization of the interaction of diosgenin with human serum albumin and α1-acid glycoprotein using biophysical and bioinformatic tools

Abstract

Diosgenin (DIO), a steroidal sapogenin with high therapeutic potential, has been shown to exhibit a myriad of pharmacologically significant properties and is commonly used as a template for synthesizing steroidal drugs. The efficacy of bioactive compounds as a potential drug depends mainly upon their interaction with proteins in the circulatory system. Therefore, the interaction of DIO with the major carrier proteins in humans, i.e. human serum albumin (HSA) and α 1 -acid glycoprotein (AAG), was characterized using multispectroscopic and molecular docking techniques. Analysis of fluorescence enhancement data showed intermediate binding affinity for both DIO–HSA and DIO–AAG interactions. Circular dichroism spectral results revealed minimal conformational alterations in HSA upon DIO binding, but the effect on AAG was more significant. Competitive ligand displacement results suggested that DIO does not bind strongly to the main drug binding sites of HSA. However, DIO was found to favor binding to subdomain IB of HSA based on molecular docking data. For AAG, the binding location of DIO was determined for the two variants of AAG (A and F1*S variants) using molecular docking. For variant A, the binding site was situated in lobes I and II of the central binding pocket of the protein, while in variant F1*S, DIO was docked to a cleft on the protein surface. Hydrophobic interactions and van der Waals forces were mainly responsible for complexation between DIO and both proteins. Additionally, there was involvement of hydrogen bonding between DIO and both variants of AAG, but not between DIO and HSA. • AAG binds to DIO with slightly stronger affinity than HSA. • Hydrophobic forces are mainly responsible for DIO binding to both proteins. • DIO binds to HSA at subdomain IB. • DIO binds to variant F1*S of AAG at a cleft at the surface. • DIO binds to variant A of AAG at the central cavity.