Planta Med 2014; 80 - P2O2
DOI: 10.1055/s-0034-1394998

Hemisynthesis of glycosylated derivatives of pheophorbide a

E Cieckiewicz 1, L Angenot 1, V Mathieu 3, B Pirotte 2, P de Tullio 2, M Frédérich 1
  • 1Université de Liège, CIRM, Laboratory of Pharmacognosy (B36), Av de l'Hôpital, 1, 4000 Liège, Belgium
  • 2Université de Liège, CIRM, Laboratory of Medicinal Chemistry (B36), Av de l'Hôpital, 1, 4000 Liège, Belgium
  • 3Laboratoire de Cancérologie et Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Campus de La Plaine, CP205/1, Boulevard du Triomphe, 1050 Bruxelles, Belgium

Pheophorbide a is a photoactivable compound isolated from Carpinus betulus leaves EtOAc extract [1]. The photoactivable compounds, like the pheophorbide a are able to be used in photodynamic therapy. The photodynamic therapy (PDT) requires the combination of tissue oxygen, visible light and photosensitizer. Like many other photosensitizers, pheophorbide a doesn't have selectivity toward tumoral tissues [2]. To circumvent this drawback, we decided to synthesize a conjugated form of pheophorbide a with carbohydrates moieties known for their affinity to galectins [3]. These are a family of carbohydrate-binding proteins with an affinity for β-galactosides. Galectin-1 is particularly overexpressed in several tumors and plays important roles in the progression and dissemination of tumoral cells [3]. The present work details the semisynthesis of original glycosylated derivatives of pheophorbide a. Organic synthesis were monitored by analytical method including solid-phase extraction (SPE) liquid chromatography (LC) coupled with Nuclear Magnetic Resonance Spectroscopy (NMR) (LC-SPE-NMR). The combination of LC-SPE-NMR facilitated direct identification of mass-limited semisynthetic products while the isolation and purification by traditional methods failed to identify products of interest. Indeed, the semisynthesis were performed on small amounts of pheophorbide a because of the low percentage of the photosensitizer in C. betulus leaves EtOAc extract [1]. The use of LC-SPE-NMR allows a fast structure-elucidation for semisynthetic compounds present in small quantities in mixtures. MS analysis completed the data required for complete structural identification.

Keywords: Photodynamic therapy, pheophorbide a, glycosylated derivatives, Carpinus betulus, galectin 1

References:

[1] Cieckiewicz E, Angenot L, Gras T, Kiss R, Frédérich M. Potential anticancer activity of young Carpinus betulus leaves. Phytomedicine 2012; 19: 272 – 283.

[2] Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel D, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson BC, Golab J. Photodynamic therapy of cancer: an update. CA Cancer J Clin 2011; 61: 250 – 281.

[3] Rabinovich G. Galectin-1 as a potential cancer target. Br J cancer 2005; 92: 1188 – 1192.