The 2-aminoglucosamide motif improves cellular uptake and photodynamic activity of tetraphenylporphyrin.

Benoit Di Stasio (1, 2) , Céline Frochot (1) , Dominique Dumas (3) , Pascale Even (1) , Jurriaan Zwier (4) , Audrey Müller (1) , Jacques Didelon (2) , François Guillemin (2) , Marie-Laure Viriot (1) , Muriel Barberi-Heyob (2)

1 DCPR - Département de Chimie Physique des Réactions
2 Inserm U569 - Epidémiologie, Démographie et Sciences Sociales : santé reproductive, sexualité et infection à VIH
3 LEMTA - Laboratoire d'Energétique et Mécanique Théorique et Appliquée
4 Institute of Molecular Chemistry

Several strategies have been proposed to improve the efficiency of photosensitizers used in photodynamic therapy (PDT). In this context, the synthesis of mono- (1) and di-glucosylated (2) porphyrins, and mono-glucosylated chlorin (3) was performed. HT29 human adenocarcinoma cells were significantly more sensitive to asymmetric and less hydrophobic glucosylated photosensitizers-mediated PDT (1, 3), compared to tetraphenylporphyrin (TPP). The lowest photosensitivity observed for TPP was consistent with the lowest uptake. Moreover, the most pronounced photodynamic activity measured for 3 was in relation with the improvement of cellular uptake, the singlet oxygen quantum yield and the high extinction coefficient value at 650 nm compared to porphyrins. Cellular localization analysis showed that 1 and 3 accumulated mainly inside the endoplasmic reticulum.

Mots clés: Porphyrin; Chlorin; Targeting; In vitro; Photodynamic therapy; Glucosylation

Domaines: Chimie-Physique [physics.chem-ph]

Benoit Di Stasio, Céline Frochot, Dominique Dumas, Pascale Even, Jurriaan Zwier, et al.. The 2-aminoglucosamide motif improves cellular uptake and photodynamic activity of tetraphenylporphyrin.. European Journal of Medicinal Chemistry, 2005, 40, pp.1111-1122. ⟨10.1016/j.ejmech.2005.04.007⟩. ⟨hal-00200179⟩