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Title

Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells

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Published in Bioorganic Chemistry. 2018, vol. 78, p. 372-380
Abstract Treatment of cancer cells by clinically approved hexyl ester of 5-aminolevulinic acid (ALA-Hex) induces accumulation of fluorescent porphyrins in tumors. This allows fluorescence photodiagnosis (PD) of bladder cancer by blue light illumination. However, PD of other cancers is hampered by acute toxicity of the compound limiting its use to local applications. We have designed and synthesized a new prodrug of ALA-Hex that tackles the stability-activity paradox of amino-modified 5-ALA prodrugs. The glucuronide prodrug Glu-ALA-Hex demonstrates excellent stability under physiological conditions and activation in the presence of the target enzyme. β-glucuronidase-triggered release of 5-ALA is programmed to yield fluorescence in tumor environment with elevated β-glucuronidase activity, a characteristic of many solid tumors. Glu-ALA-Hex produces similar levels of fluorescence as ALA-Hex in breast cancer MCF7 cells in vitro but with much lower non-specific cell toxicity.
Keywords 5-Aminolevulinic acidProdrugsBeta-glucuronidaseFluorescencePhotodiagnosisBreast cancer
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PMID: 29627657
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Article (Author postprint) (756 Kb) - private document Private access (until 2019-04-11)
Other version: http://linkinghub.elsevier.com/retrieve/pii/S0045206818300245
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Research group Technologie pharmaceutique
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(ISO format)
HERCEG, Viktorija et al. Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells. In: Bioorganic Chemistry, 2018, vol. 78, p. 372-380. https://archive-ouverte.unige.ch/unige:104599

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Deposited on : 2018-05-22

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