Synthesis and biological evaluation of cationic TopFluor cholesterol analogues.

Abstract

Cholesterol is not only a major component of the cell membrane, but also plays an important role in a wide range of biological processes and pathologies. It is therefore crucial to develop appropriate tools for visualizing intracellular cholesterol transport. Here, we describe new cationic analogues of BODIPY-Cholesterol (TopFluor-Cholesterol, TF-Chol), which combine a positive charge on the sterol side chain and a BODIPY group connected via a C-4 linker. In contrast to TF-Chol, the new analogues TF-1 and TF-3 possessing acetyl groups on the A ring (C-3 position on steroid) internalized much faster and displayed slightly different levels of intracellular localization. Their applicability for cholesterol monitoring was indicated by the fact that they strongly label compartments with accumulated cholesterol in cells carrying a mutation of the Niemann-Pick disease-associated cholesterol transporter, NPC1.

• Authors: Michal Jurášek, Jan Valečka, Ivan Novotný, Zdeněk Kejík, Jan Fähnrich, Anna Marešová, Jan Tauchen, Petr Bartůněk, Bohumil Dolenský, Milan Jakubek, Pavel B Drašar, Jarmila Králová
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 117 Pg. 105410 (12 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 34700109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
• Boron Compounds
• Cholesterol

Topics

• Biological Transport
• Boron Compounds (analysis, chemical synthesis, chemistry, metabolism)
• Cell Line
• Cholesterol (analogs & derivatives, analysis, chemical synthesis, metabolism)
• Humans
• Optical Imaging