Fingolimod phosphoramidate prodrugs: Synthesis, photophysical characterisation and lipid bilayer interaction of fluorescent tagged Prodrug

Pertusati, Fabrizio ORCID: https://orcid.org/0000-0003-4532-9101, Serpi, Michaela ORCID: https://orcid.org/0000-0002-6162-7910, Morozzi, Chiara, James, Edward, Renno, Giacomo, Cardano, Francesca and Fin, Andrea 2024. Fingolimod phosphoramidate prodrugs: Synthesis, photophysical characterisation and lipid bilayer interaction of fluorescent tagged Prodrug. Journal of Molecular Structure 1312 (2) , 138614. 10.1016/j.molstruc.2024.138614

PDF - Published Version Available under License Creative Commons Attribution. Download (3MB)

Abstract

FTY720 (Fingolimod, Gilenya, 1), a structural analog of sphingosine (2) was the first orally administered drug approved for the treatment of multiple sclerosis (MS). However, the phosphate derivative of Fingolimod, namely Fingolimod-1-phosphate (FTY720-1P, 3) is the biologically active molecule in MS as well as in various lysosomal storage diseases such as mucolipidosis IV and Nieman-Pick. In all cases, Fingolimod requires to be phosphorylated, resembling the natural sphingosine phosphate (4), to accomplish its therapeutic/biological effects. Here, we report the synthesis of a small library of prodrugs that could provide the efficient delivery of 3, the bioactive species. Moreover, to gain insight about the biological behaviour of these novel candidates within human body such as cell and brain blood barrier penetration we have prepared and spectroscopically characterised a fluorescent tagged version of one of the new prodrugs. The behavior of our prodrugs with respect to biological membranes was evaluated by studying the interaction between the fluorescent prodrug 18 and DOPC/DPPC liposome models.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Start Date: 2024-05-20
Publisher:	Elsevier
ISSN:	0022-2860
Date of First Compliant Deposit:	24 May 2024
Date of Acceptance:	11 May 2024
Last Modified:	24 May 2024 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/169153

Actions (repository staff only)

Edit Item