Investigation of the interaction between S-isoalkyl derivatives of the thiosalicylic acid and human serum albumin

Abstract

S-isoalkyl derivatives of thiosalicylic acid (isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) were selected in order to investigate the binding interaction with the human serum albumin (HSA) using different spectroscopic methods and molecular docking simulation. Association constants and number of binding sites were used to analyze the quenching mechanism. The experimental results showed that the fluorescence quenching of HSA by L1, L2 and L3 occurs because of static quenching and that binding processes were spontaneous, with the leading forces in bonding by hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Fluorescence spectroscopy, UV-Vis spectroscopy and synchronous fluorescence spectroscopy showed that ligands (L1, L2 and L3) can bind to HSA and that the binding of ligands induced some microenvironmental and conformational changes in HSA. The calculated distance between the donor and the acceptor according to fiFörster’s theory confirms the energy transfer efficiency between the acceptor and HSA. Results of site marker competitive experiments showed that the tested compounds bind to HSA in domain IIA (Site I). Molecular dynamics and docking calculations demonstrated that L3 binds to the Sudlow site I of HSA with lower values of binding energies compared to L1 and L2, indicating the formation of the most stable ligand-HSA complex. Understanding the binding mechanisms of S-isoalkyl derivatives of the thiosalicylic acid to HSA may provide valuable data for the future studies of their biological activity and application as potential antitumor drugs.

Communicated by Ramaswamy H. Sarma

Keywords:

• Human serum albumin
• thiosalicylic acid
• isoalkyl derivatives
• spectroscopic measurements
• docking simulations

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia through Grant Agreements with University of Kragujevac-Faculty of Medical Sciences (No: 451-03-47/2023-01/200111) and with Faculty of Science (No: 451-03-47/2023-01/200122), Serbian Science and Diaspora Collaboration Program: (Project acronym: TransMeCo), and Faculty of Medical Sciences, University of Kragujevac (Junior Project 08/19). This research was funded the program grant P1-0175 the Slovenian Research Agency (ARRS). We thank the EN-FIST Centre of Excellence, Dunajska 156, SI-1000 Ljubljana, Slovenia, for the use of a SuperNova diffractometer.