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1 November 2003 New 5-Aminolevulinic Acid Esters—Efficient Protoporphyrin Precursors for Photodetection and Photodynamic Therapy
H. Brunner, F. Hausmann, R. Knuechel
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Abstract

Photodetection (PD) and photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA)–induced protoporphyrin IX (PPIX) accumulation are approaches to detect and treat dysplasia and early cancer in the gastrointestinal tract and in the urinary bladder. Because ALA-induced PPIX production is limited, we synthesized ALA ester hydrochlorides 3–22 and tested them in two different in vitro models (gastrointestinal tract: HT29–CCD18; urinary bladder: J82–UROTSA). PPIX accumulation after incubation with 0.12 mmol/L for 3 h and PPIX accumulation as a function of different incubation times were measured using flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to check cellular dark toxicity. Phototoxicity after irradiation was tested. ALA nonafluorohexylester hydrochloride 11, ALA thiohexylester hydrochloride 13 and ALA dibenzyldiester dihydrochloride 19 induced appreciably increased PPIX levels and showed improved phototoxicity compared with the references ALA hydrochloride 1, ALA hexylester hydrochloride 3 and ALA benzylester hydrochloride 4. Thus, the new compounds 11, 13 and 19 are promising compounds for PD and PDT.

H. Brunner, F. Hausmann, and R. Knuechel "New 5-Aminolevulinic Acid Esters—Efficient Protoporphyrin Precursors for Photodetection and Photodynamic Therapy," Photochemistry and Photobiology 78(5), 481-486, (1 November 2003). https://doi.org/10.1562/0031-8655(2003)078<0481:NAAEPP>2.0.CO;2
Received: 14 May 2003; Accepted: 1 August 2003; Published: 1 November 2003
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