Human serum albumin subdomain IB is physiologically adapted for payloading homopterocarpin to human aldehyde dehydrogenase: Combinatorial in vitro and in silico approaches

The in vitro interactions of homopterocarpin, a potent antioxidant and anti-ulcerative isoflavonoid, with human serum albumin (HSA) and human aldehyde dehydrogenase (hALDH) were explored using various spectroscopic methods, in silico and molecular dynamic (MD) studies. The result showed that homopterocarpin quenched the intrinsic fluorescences of HSA and hALDH. The interactions were entropically favorable, driven primarily by hydrophobic interactions. The proteins have one binding site for the isoflavonoid. This interaction increased the proteins hydrodynamic radii by over 5% and caused a slight change in HSA surface hydrophobicity Homopterocarpin preferentially binds to HSA subdomain IB with a binding affinity of -10.1 kcal/mol before interaction stoke with hALDH (-8.4 kcal/mol). HSA-homopterocarpin complex attained pharmacokinetic-pharmacodynamics reversible equilibration time faster than ALDH-homopterocarpin. However, the probable and eventual therapeutic effect of homopterocarpin is the mixed inhibition ALDH activity having a Ki value of 20.74 mu M. The MD results revealed the stabilization of the complex in HSA-homopterocarpin and ALDH-homopterocarpin from their respective spatial structures of the complex. The findings of this research will provide significant benefits in understanding the pharmacokinetics characteristics of homopterocarpin at the clinical level.

Automated summary

This study investigated the in vitro interactions of a potent antioxidant and anti-ulcerative isoflavonoid, homopterocarpin, with human serum albumin (HSA) and human aldehyde dehydrogenase (hALDH) using various spectroscopic methods, in silico and molecular dynamic (MD) studies. The results showed that homopterocarpin quenched the intrinsic fluorescences of HSA and hALDH and the interactions were mainly driven by hydrophobic interactions. The binding affinity of homopterocarpin to HSA was higher than to hALDH, and the complex between HSA and homopterocarpin exhibited faster reversible equilibration time compared to ALDH-homopterocarpin complex. The findings of this research have significant implications for understanding the pharmacokinetics characteristics of homopterocarpin at the clinical level.