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Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy

Battah, S; Hider, RC; MacRobert, AJ; Dobbin, PS; Zhou, T; (2017) Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy. Journal of Medicinal Chemistry , 60 (8) pp. 3498-3510. 10.1021/acs.jmedchem.7b00346. Green open access

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Abstract

Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.

Type: Article
Title: Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.jmedchem.7b00346
Publisher version: http://dx.doi.org/10.1021/acs.jmedchem.7b00346
Language: English
Additional information: This is an open access article published under a Creative Commons Attribution (CC-BY) License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Keywords: Photodynamic Therapy (PDT); 5-aminolaevulinic acid (ALA); iron chelator; hydroxypyridinone (HPO); protoporphyrin IX (PpIX)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1549615
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