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  • Title: A study of the stability of tri(glucosyloxyphenyl)chlorin, a sensitizer for photodynamic therapy, in human colon tumoural cells: a liquid chromatography and MALDI-TOF mass spectrometry analysis.
    Author: Laville I, Pigaglio S, Blais JC, Loock B, Maillard P, Grierson DS, Blais J.
    Journal: Bioorg Med Chem; 2004 Jul 01; 12(13):3673-82. PubMed ID: 15186852.
    Abstract:
    Asymmetrical glycoconjugated tetrapyrrolic macrocycles are under study as efficient sensitizers for photodynamic therapy (PDT). In this context, tri(meta-O-beta-glucopyranosyloxyphenyl)chlorin [TPC(m-O-Glu)(3)] 2a/3a was found to be four times more photoactive in vitro than Foscan. In a further study of this interesting glycoconjugate, its metabolism by cellular glycosidases in HT29 cells has to be explored. Cellular extracts of HT29 cells incubated with TPC(m-O-Glu)(3) (24h, 6microM) were analyzed by MALDI-TOF mass spectrometry and high performance liquid chromatography (HPLC). In MALDI-TOF mass spectra, the presence of compounds distinct from TPC(m-O-Glu)(3) (m/z 1151) were observed at m/z 989, 827 and 665 corresponding to the loss of one, two or three glucose units (162u) and were be ascribed to TPC(m-OH)(m-O-Glu)(2) 2/3b,b',b", TPC(m-OH)(2)(m-O-Glu) 2/3c,c',c" and TPC(m-OH)(3) isomers 2d/3d, respectively. The porphyrins resulting from chlorin oxidation TPP(m-O-Glu)(3) 4a, TPP(m-OH)(m-O-Glu)(2) 4b,b", TPP(m-OH)(2)(m-O-Glu) 4c,c" and TPP(m-OH)(3) 4d were also observed. The HPLC profile (lambda(anal)=420 nm) showed eight peaks consistent with mass spectra. The kinetics of deglucosylation was studied from HPLC profiles between 1 and 48h incubation. The concentration of triglucoconjugated and diglucoconjugated molecules was maximum around 3 and 8h incubation, respectively, whereas, totally deglucosylated species appeared only after incubation for more than 10h. The fully deglycosylated porphyrin TPP(m-OH)(3) is the final metabolite, being observed at a concentration 15 times higher than that of the remaining TPC(m-O-Glu)(3) 2a/3a. Compared to the photobiological activity of the parent molecule [TPC(m-O-Glu)(3)], a three times higher TPP(m-OH)(3) concentration was necessary to observe a similar in vitro photoactivity.
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