Interaction of Cationic Protoberberine Alkaloids with Human Serum Albumin. No Spectroscopic Evidence on Binding to Sudlow’s Site 1

Abstract

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.

Interaction of 1-pyrene sulfonic acid sodium salt with human serum albumin

“…However, the results of such studies may be difficult for unambiguous interpretation if absorption and fluorescence spectra of HSA significantly overlap with the ligand absorption spectrum, what is often the case in drug containing systems. For example, we have recently shown [16] that changes in HSA fluorescence spectra observed with addition of protoberberine alkaloids reflect solely inner filter effects, and not the drug binding to site 1 as reported in literature [17,18].…”

“…The signal from each sample was acquired up to 1×10 4 counts in the peak. The instrument response function was recorded by collecting the light scattered from a Ludox silica suspension, and used for subsequent deconvolution of the fluorescence signal; see [16] for more details.…”

Binding of a potential anti-hepatoma drug cis,cis,trans-[Pt(NH3)2Cl2(O2CCH2CH2COOH)-(OCONHC16H33)] with serum albumin – thermodynamic and conformational investigations

“…[11][12][13] The protein was reported to serve as a transporter for a variety of endogenous and exogenous compounds such as drugs, fatty acids and dyes in the bloodstream. [11][12][13] The protein was reported to serve as a transporter for a variety of endogenous and exogenous compounds such as drugs, fatty acids and dyes in the bloodstream.…”

Synthesis of Tailed Metalloporphyrins Modified with 2‐Chloronicotinic Acid and Interactions with Human Serum Albumin

“…Study of the interactions of HSA with drug molecules requires interdisciplinary research, being a relevant topic in life sciences, pharmacology, chemistry, and medicine. [21][22][23][24][25][26][27][28][29][30][31] When a porphyrin enters a living organism, it may combine with a protein such as HSA, and this will control its accumulation, distribution, and metabolism in the body. Therefore, there have been numerous studies on the interaction of porphyrins with HSA.…”

“…Understanding the interaction between drug molecules and HSA, including the transportation and metabolism of drugs in the human body, could facilitate the identification of novel drugs and the improvement of existing medicines. Study of the interactions of HSA with drug molecules requires interdisciplinary research, being a relevant topic in life sciences, pharmacology, chemistry, and medicine . When a porphyrin enters a living organism, it may combine with a protein such as HSA, and this will control its accumulation, distribution, and metabolism in the body.…”