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Unravelling the interaction mechanism between clioquinol and bovine serum albumin by multi-spectroscopic and molecular docking approaches.

Authors
  • Tantimongcolwat, Tanawut1
  • Prachayasittikul, Supaluk2
  • Prachayasittikul, Virapong3
  • 1 Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhonpathom 73170, Thailand. Electronic address: [email protected] , (Thailand)
  • 2 Center for Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Nakhonpathom 73170, Thailand. , (Thailand)
  • 3 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhonpathom 73170, Thailand. , (Thailand)
Type
Published Article
Journal
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
Publication Date
Jun 05, 2019
Volume
216
Pages
25–34
Identifiers
DOI: 10.1016/j.saa.2019.03.004
PMID: 30865872
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Clioquinol has recently been proposed for the treatment of Alzheimer's disease. It is able to diminish β-amyloid protein aggregation and to restore cognition of Alzheimer's mice. However, its therapeutic benefits for Alzheimer's disease in human remain controversy and need further confirmation. Herein, we have explored the interaction mechanism of clioquinol toward bovine serum albumin (BSA) by means of multi-spectroscopic and docking simulation approaches. Clioquinol interacts with BSA by a combined mechanism of static and dynamic processes. Application of the Hill's equation to fluorescence quenching experiment revealed that the binding constant of the BSA-clioquinol complex is extremely high at 108 M-1 level. Competitive displacement and docking analysis consistently suggested that there are the multiple binding modes of clioquinol toward BSA. Competitive binding study showed that clioquinol shares the binding sites with ibuprofen and digitoxin on albumin, referring to be site II and site III binding compounds. Besides, partial binding in site I was also observed. Docking simulation confirmed that clioquinol favors to bind in site I, site II, site III, fatty acid binding site 5, and the protein cleft between subdomain IB and IIIB of the BSA. Due to its small size and electric dipole property, clioquinol may easily fit in multiple pockets of the BSA. Our finding suggests the potential role of BSA as a clioquinol carrier in the vascular system. Nonetheless, clioquinol-induced BSA aggregation has been observed by the three-dimensional fluorescence technique. This phenomenon may not only impair the BSA, but may also affect other endogenous proteins, which eventually causes adverse effects to human. Therefore, the redesigned or modified molecular structure of clioquinol may reduce its toxicity and improve its bioavailability. Copyright © 2019 Elsevier B.V. All rights reserved.

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