The Influence of Oxidative Stress on Serum Albumin Structure as a Carrier of Selected Diazaphenothiazine with Potential Anticancer Activity

Abstract

Albumin is one of the most important proteins in human blood. Among its multiple functions, drug binding is crucial in terms of drug distribution in human body. This protein undergoes many modifications that are certain to influence protein activity and affect its structure. One such reaction is albumin oxidation. Chloramine T is a strong oxidant. Solutions of human serum albumin, both non-modified and modified by chloramine T, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. 10H-3,6-diazaphenothiazine (DAPT) has anticancer activity and it has been studied for the first time in terms of binding with human serum albumin—its potential as a transporting protein. Using fluorescence spectroscopy, in the presence of dansylated amino acids, dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), DAPT binding with two main albumin sites—in subdomain IIA and IIIA—has been evaluated. Based on the conducted data, in order to measure the stability of DAPT complexes with human (HSA) and oxidized (oHSA) serum albumin, association constant (Ka) for ligand-HSA and ligand-oHSA complexes were calculated. It has been presumed that oxidation is not an important issue in terms of 10H-3,6-diazaphenothiazine binding to albumin. It means that the distribution of this substance is similar regardless of changes in albumin structure caused by oxidation, natural occurring in the organism.

Spectroscopic Studies of Quinobenzothiazine Derivative in Terms of the In Vitro Interaction with Selected Human Plasma Proteins. Part 1

“…Similar to the present study, Maciążek–Jurczyk et al [ 22 ] used spectral parameter A and FWHM values to analyze the changes in the tertiary structure of native and oxidized human serum albumin. They observed a decrease in the values of spectral parameter A and FWHM, pointing to the increase in the environmental hydrophobicity of tyrosyl and tryptophanyl residues.…”

“…The analysis of protein fluorescence quenching by increasing ligand concentration allows the monitoring of intermolecular interactions. A major requirement for fluorescence quenching is the appropriate distance between the excited fluorophore and the ligand [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

“…The albumin structure consists of three α-helical domains, I–III, and each of them is divided into subdomains A and B [ 6 ]. In the albumin molecule, there are two sites with a characteristic structure and high affinity for drug binding called Sudlow sites I and II located in hydrophobic cavities in subdomains IIA and IIIA [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Pre-Formulation Studies: Physicochemical Characteristics and In Vitro Release Kinetics of Insulin from Selected Hydrogels

“…Spectral parameter A ( ) was used because of its sensitivity to small changes in insulin maximum fluorescence. As in the present study, Maciążek–Jurczyk et al [ 81 ], based on the parameters A as well as FWHM values, analyzed the changes in the tertiary structure of native and oxidized human serum albumin. They observed the decrease in the values of parameters A and FWHM, pointing to the increase in tyrosyl residues and environmental hydrophobicity.…”

Lipophilicity and Pharmacokinetic Properties of New Anticancer Dipyridothiazine with 1,2,3-Triazole Substituents

“…Dipyridothiazines are modified phenothiazine structures into which two pyridine rings have been introduced instead of two benzene rings [13]. In recent years, significant and highly promising anticancer activities of these heterocyclic systems have been proven [14][15][16][17]. Additionally, selected derivatives of this group showed immunomodulatory and antioxidant potential [18,19].…”