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Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy

Battah, Sinan and Hider, Robert C and MacRobert, Alexander J and Dobbin, Paul S and Zhou, Tao (2017) 'Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy.' Journal of Medicinal Chemistry, 60 (8). 3498 - 3510. ISSN 0022-2623

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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.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 29 Jun 2017 14:43
Last Modified: 13 Aug 2019 21:15
URI: http://repository.essex.ac.uk/id/eprint/19916

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