Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.

Abstract

5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA-HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA-HPO conjugates in photodynamic therapy.

• Authors: Chun-Feng Zhu, Sinan Battah, Xiaole Kong, Brandon J Reeder, Robert C Hider, Tao Zhou
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 3 Pg. 558-61 (Feb 01 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 25556100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Photosensitizing Agents
• Prodrugs
• Pyridones
• Aminolevulinic Acid

Topics

• Aminolevulinic Acid (chemistry)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Design
• Female
• Humans
• Light
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, therapeutic use, toxicity)
• Prodrugs (chemical synthesis, therapeutic use, toxicity)
• Pyridones (chemistry)