Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity dependent on photoactivation

G. Berkovitch; A. Nudelman; B. Ehenberg; A. Rephaeli; Z. Malik

doi:10.1117/12.822703

13 July 2009 Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity dependent on photoactivation

G. Berkovitch, A. Nudelman, B. Ehenberg, A. Rephaeli, Z. Malik

Author Affiliations +

Proceedings Volume 7380, Photodynamic Therapy: Back to the Future; 73800Z (2009) https://doi.org/10.1117/12.822703
Event: 12th World Congress of the International Photodynamic Association, 2009, Seattle, Washington, United States

Abstract

New approaches to PDT using multifunctional 5-aminolevulinic acid (ALA) based prodrugs activating mutual routes of toxicity are described. We investigated the mutual anti-cancer activity of ALA prodrugs which upon metabolic hydrolysis by unspecific esterases release ALA, formaldehyde or acetaldehye and the histone deacetylase inhibitor (HDACI) butyric acid. The most potent prodrug in this study was butyryloxyethyl 5-amino-4-oxopentanoate (AN-233) that stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells and generated an efficient photodynamic destruction. AN-233 induced a considerable high level of intracellular ROS in the cells following light irradiation, reduction of mitochondrial activity, dissipation of the mitochondrial membrane potential resulting in necrotic and apoptotic cell death. The main advantage of AN-233 over ALA stems from its ability to induce photodamage at a significantly lower dose than ALA.

Citation Download Citation

G. Berkovitch, A. Nudelman, B. Ehenberg, A. Rephaeli, and Z. Malik "Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity dependent on photoactivation", Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 73800Z (13 July 2009); https://doi.org/10.1117/12.822703

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