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Design and synthesis of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates for photodynamic therapy: enhancement of protoporphyrin IX production and photo-toxicity in tumor cells

Zhou, T; Shao, L-L; Battah, S; Zhu, C-F; Hider, RC; Reeder, BJ; Jabeen, A; ... Liang, X; + view all (2016) Design and synthesis of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates for photodynamic therapy: enhancement of protoporphyrin IX production and photo-toxicity in tumor cells. MedChemComm , 7 (6) pp. 1190-1196. 10.1039/c6md00040a. Green open access

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Abstract

5-Aminolaevulinic acid (ALA) and its derivatives have been widely used in photodynamic therapy (PDT) as precursors of the photosensitizer, protoporphyrin IX (PpIX) in dermatology and urology. However, ALA-PDT is limited by the low bioavailability of ALA due to the fact that ALA is poorly absorbed by cells by virtue of its zwitterionic nature at physiological pH. In order to improve the therapeutic effect and induce higher levels of PpIX, a series of ALA prodrugs were synthesized by the conjugation of ALA to 3-hydroxypyridin-4-one (HPO) iron chelator using an amino acid linkage via amide bonds. Pharmacokinetic studies indicated that one ALA–HPO conjugate significantly enhanced PpIX production in a range of tumor cell lines over ALA alone or the co-administration of ALA and CP94 (1,2-diethyl-3-hydroxypyridin-4-one). The intracellular porphyrin fluorescence levels showed good correlation with cellular photo-toxicity following light exposure, suggesting the potential application of the ALA–HPO conjugates in photodynamic therapy.

Type: Article
Title: Design and synthesis of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates for photodynamic therapy: enhancement of protoporphyrin IX production and photo-toxicity in tumor cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/c6md00040a
Publisher version: http://dx.doi.org/10.1039/c6md00040a
Language: English
Additional information: © Royal Society of Chemistry 2016
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Chemistry, Medicinal, Pharmacology & Pharmacy, Delta-Aminolevulinic-Acid, Iron-Chelating Agents, In-Vivo, Accumulation, Derivatives, Fluorescence, Efficacy, Cancer, Esters, 5-ALA
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/1509460
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