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

Article Article scientifique Article Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells eng 2018 author Herceg Viktorija 768015 author Adriouach Souad 869600 author Janikowska Karolina 824204 author Allémann Eric 0000-0002-6598-9521 26730 author Lange Norbert 135650 author Babic Andréj 742457 372-380 10.1016/j.bioorg.2018.03.020 29627657 0045-2068 http://linkinghub.elsevier.com/retrieve/pii/S0045206818300245 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. 5-Aminolevulinic acid Prodrugs Beta-glucuronidase Fluorescence Photodiagnosis Breast cancer Dewey 615 31 Section des sciences pharmaceutiques 17 false 883 Technologie pharmaceutique Bioorganic Chemistry 78 425eb677-f7c5-4976-b0ab-03e53b646fe1 Article (Accepted version) Public Herceg-GLU-ALA-Hex.pdf 774259 application/pdf CC BY-NC Private 2019-04-11 openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells	Bioorganic Chemistry			2018	577	488

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Janikowska, Karolina