Biophysical insight into the interaction mechanism of 4-bromo-N-(thiazol-2-yl)benzenesulfonamide and human serum albumin using multi-spectroscopic and computational studies.

Autor: Ayimbila F; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand., Phopin K; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand., Ruankham W; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand., Pingaew R; Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110 Thailand., Prachayasittikul S; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand., Prachayasittikul V; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand., Tantimongcolwat T; Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700 Thailand. Electronic address: tanawut.tan@mahidol.ac.th.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2024 Nov 09; Vol. 204, pp. 106961. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1016/j.ejps.2024.106961
Abstrakt: 4-Bromo-N-(thiazol-2-yl)benzenesulfonamide (1) is enriched with bioactive components and is highlighted for its pharmacological properties. However, its pharmacokinetic characteristics are yet to be reported. The interaction of compound 1 with carrier proteins in the bloodstream is an important factor that affects its potential therapeutic efficacy. This study aimed to elucidate the pharmacokinetic mechanisms of compound 1 in relation to human serum albumin (HSA) using multi-spectroscopic and computational techniques. Its predicted drug-like properties revealed no mutagenicity, although potential hepatotoxicity and interactions with certain cytochrome P450 enzymes were observed. Spectroscopic analyses extensively provided the interaction between HSA and 1 through a static fluorescence quenching mechanism with spontaneous hydrophobic interactions and hydrogen bonding. The binding constant of the HSA‒1 complex was relatively moderate to strong at a level of 10 6 M -1 . Various spectroscopic techniques including ultraviolet-visible, Fourier transform infrared, and circular dichroism spectroscopies indicated that its binding induced alteration in the α-helix content of HSA. Competitive binding and molecular docking studies designated the preferential binding of 1 to sub-structural domain IIA binding site I of HSA. Molecular dynamic simulations further illustrated the formation of a stable complex between 1 and HSA, accompanied by conformational changes in the protein. Importantly, esterase capacity of the HSA‒1 complex increased compared to the free HSA. Therefore, elucidation of the HSA‒1 binding mechanism provides valuable insights into the pharmacokinetics, suggesting potential benefits for the further development of 1 as a therapeutic agent.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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