Combined spectroscopic and computational approaches for the recognition of bioactive flavonoid 6-hydroxyflavone by human serum albumin: Effects of non-enzymatic glycation in the binding

Serum albumin's stability and function are influenced by several structural changes. Non-enzymatic glycation (NEG) is one of the mechanisms which impairs and changes the physiological function of serum albumins. Advanced glycation end products (AGEs) are produced in long-term hyperglycamia and are responsible for structural cell and tissue failures associated with a variety of health disorders. The objective of our study is to assess the consequences of NEG in the molecular recognition of bioactive flavonoid 6-hydroxyflavone by human serum albumin (HSA) using various spectroscopic and computational analyses. UV–visible study revealed the possibility of ground-state interaction of 6HF with HSA/glycated HSA (gHSA) and the presence of static quenching mechanism have been supported by the quenching parameters derived from fluorescence quenching studies at three temperatures (290, 300 and 310 K). Due to glycation-related modulations around the binding sites of HSA, 6HF's interaction with gHSA has higher binding constants than that with HSA. The negative ΔG° showed the spontaneous nature of binding. Positive ΔS° and negative ΔH° indicated that hydrogen bonding and hydrophobic interactions are responsible for the binding. The percentage α-helix of HSA raised in the presence of 6HF, while the effect on gHSA is minor. Site probe experiments revealed that 6HF occupies the binding sites in subdomain IIA and IIIA, but it prefers binding to subdomain IIIA of gHSA. The outcomes from the molecular docking and MD simulation also correlates with the experimental results. This study analyses the changes in the molecular recognition of 6HF by HSA after glycation, which may aid in the understanding of comparable drug pharmacodynamics and offer crucial information for future therapeutic development.