Aleksandra Owczarzy, Kacper Laprus, Andrzej Zięba, Małgorzata Maciążek-Jurczyk

Spectroscopic studies of the interaction between substance with potential anticancer activity and carrier protein

2024-12-02

Subject of study. Cancer diseases are one of the leading causes of premature death, and the number of new cases is constantly increasing. Current cancer treatment schemes using registered drugs are often insufficiently effective and, at the same time, have many side effects. For this reason, it is necessary to search for new substances with anticancer potential.

The goal of the study. The aim of this study was to analyze the interaction between 5-methyl-12H-chino[3,4-b]pyrido[5,6-e]thiazine chloride (AZMM6) and 1-acid glycoprotein and to evaluate the effect of AZMM6 on the secondary and tertiary structures of the studied protein.

Materials and methods. The studies were conducted using UV-VIS absorption spectroscopy, fluorescence spectroscopy, and circular dichroism spectroscopy. Based on the Stern-Volmer equation, for the AZMM6-AGP complex, at excitation wavelengths ex 275 nm and 295 nm, the Stern-Volmer constant (KS-V) and the bimolecular quenching constant rate (kq) were calculated. The Klotz equation was used to calculate the association constant (Ka) and the number of binding classes (n). The AZMM6 binding sites in the AGP molecule were also determined. Circular dichroism spectroscopy was used to evaluate the changes in the secondary structure of the studied protein. To analyze the changes in the environment around the aromatic amino acid residues present in AGP, the spectral parameter A, the full width at half maximum (FWHM), and the second derivative of the differential spectra were used.

Results. On the basis of the spectroscopic analyses, the determined binding constants and the nature of the interaction indicate a weak binding of AZMM6 to AGP.

Conclusions. AZMM6 binds to AGP to a small extent and, thus, it can produce therapeutic as well as a strong toxic effect. Therefore, further studies using human albumin and other plasma transport proteins are required. Moreover, another technique such as nanoITC is needed.

Keywords: 5-methyl-12H-chino[3,4-b]pyrido[5,6-e]thiazine chloride, 1 acid glycoprotein, spectroscopy UV-VIS, fluorescence spectroscopy, circular dichroism spectroscopy.

© Farm Pol, 2024, 80(7): 429–439