Spectroscopic investigation of the anticancer alkaloid piperlongumine binding to human serum albumin from the viewpoint of drug delivery

Abstract

Piperlongumine (PL) is a very promising natural agent with a high potential for cancer treatment. To overcome the poor water solubility of PL, there is a need to develop a novel water-soluble formulation in which PL is non-covalently bound to human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic techniques under simulated physiological conditions. Spectroscopic evidence showed that the interaction of PL with HSA could form a PL-HSA complex. The binding constant (K ) values increased with increasing temperature, and a similar dependence was observed for the number of binding sites (n) values. The number of PL molecules bound to HSA reached 8.1 when the temperature was raised to 308 K. Thermodynamic calculation results suggested that the binding reaction occurred spontaneously but was an entropy-driven process, and hydrophobic forces played a major role in stabilizing the complex. Furthermore, PL binding induced conformational and microenvironmental changes in HSA. Displacement studies indicated that PL and warfarin had separate binding regions in site I. Therefore, it would be possible to develop a novel water-soluble formulation involving PL and HSA. This study may provide some valuable information in terms of improving the poor water solubility of PL.

Details of the cooperative binding of piperlongumine with rat serum albumin obtained by spectroscopic and computational analyses

“…Table 1 shows that K a calculated using the fluorescence intensities at 340 nm and the areas below the spectra are in good agreement. The order of magnitude of K a is 10 4 M −1 , that according to literature corresponds to a moderate constant for albumins 7 . The number of sites (n) remained close to one, which is expected due to the first order binding equilibrium model, and the increment of K a as the temperature rises, indicates its influence on the stability of the complex.…”

“…Considering the lipophilic characteristics of PPL, its transport through plasma must be assisted by carrier proteins, such as albumin. A few works present in the literature bring the first results of the interaction of PPL with human albumin 6,7 . Nevertheless, no information about the interaction between PPL and rat serum albumin (RSA) is known.…”

Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells

“…Pharmaceutical chemists may be able to derive compounds characterized by improved anticancer activity and appropriate drug-like physicochemical parameters. In addition, the use of modern drug delivery systems may improve the efficacy and solve issues related to water solubility [33]. Recently, great efforts have been made in to optimize PL activity through physicochemical parameters, pharmacokinetics, and safety, making PL a good candidate for future anticancer therapy.…”

Experimental Approaches and Computational Modeling of Rat Serum Albumin and Its Interaction with Piperine

“…The interaction density function (IDF) method was applied to the fluorescence spectroscopy data in order to determine the binding constant, since the value of the binding constant is essential to comprehend the affinity of piperine toward RSA and therefore the efficiency of its transport in the blood stream. A moderate binding constant (10 4 –10 6 M –1 ) is desirable because it reflects an extended half-life and a better distribution of the compound in the body [28]. With the IDF method, it was possible to determine the number of sites and the existence (or otherwise) of cooperative properties between them.…”