8 research outputs found
Interaction of Cationic Protoberberine Alkaloids with Human Serum Albumin. No Spectroscopic Evidence on Binding to Sudlow’s Site 1
Physicochemical
studies on drug interactions with human serum albumin
(HSA) are relevant for elucidation, at the molecular level, of the
processes occurring in vivo. In this work using optical spectroscopic
methods (fluorescence, absorption, circular dichroism), we have investigated
aqueous HSA solutions containing pharmaceutically important isoquinoline
alkaloids, berberine and palmatine. The primary objective was to verify
whether the two compounds are located in the subdomain IIA of the
secondary HSA structure as reported in literature. We prove that the
excited state of Trp214 residue is not quenched by the alkaloids;
all observed changes in fluorescence spectra are due to inner filter
effects. Furthermore, differential absorption spectra indicate that
the ligands remain in a waterlike microenvironment. We infer that
bound alkaloid molecules are located at the protein/water interface.
Yet, such binding mode can induce some unfolding of the HSA molecule
detectable in the far-UV circular dichroism (CD) spectra. We have
also performed, for the first time, pulse radiolysis studies of hydrated
electron scavenging in the HSA/alkaloid systems and have measured
steady-state absorption spectra of irradiated samples. The results
reveal that neither berberine nor palmatine is effectively protected
by the protein against one-electron reduction, which is consistent
with the aforementioned conclusion