Synthesis, photophysical properties and sugar-dependent in vitro photocytotoxicity of pyrrolidine-fused chlorins bearing S-glycosides

Eight S-glycosylated 5,10,15,20-tetrakis(tetrafluorophenyl)porphyrins (1a', 1b', la and 11b (a: S-glucosylated, b: S-galactosylated)) and their 1,3-dipolar cycloadducts, i.e. chlorins 2a', 2b', 2a and 2b were prepared by nucleophilic substitution of the pentafluorophenyl groups with S-glycoside. These photosensitizers were characterized by (1)H, (13)C and (91)F NMR spectroscopies and elemental analysis. The photocytotoxicity of the S-glycosylated photosensitizers and the parent porphyrin (1) and chlorin (2) was examined in HeLa cells. Photosensitizers 1, 2, 1a', 1b', 2a, and 2b, showed no significant photocytotoxicity at the concentration of 0.5 mu M, while the deprotected photosensitizers la, 1b, 2a and 2b were photocytotoxic. The strong inhibition by sodium azide of the photocytotoxicity of these photosensitizers suggested that 102 is the main mediator. The S-glucosylated photosensitizers; la and 2a showed higher photocytotoxicity than S-galactosylated 1b and 2b, respectively. The cellular uptake of la and 2a increased up to 24 h, while that of 1b and 2b was saturated by 12 h. (c) 2009 Elsevier B.V. All rights reserved.