Glycosylated porphyrin derivatives and their photodynamic activity in cancer cells

The present study reports the design and synthesis of nine C ₂-symmetric 5,15-[bis(arayl)]-10α,20β-[bis(1,2:3,4-di-O- isopropylidene-α-d-galactopyranose-6-yl)]porphyrins (3-11) bearing electron donating or electron withdrawing substituents and a D ₂-symmetric 5α,10β,15α,20β-tetrakis(1,2:3,4-di- O-isopropylidene-α-d-galactopyranose-6-yl)porphyrin (12). In the system we design, the C₆ of pyranose sugar is elegantly fused into the porphyrin core as meso carbon, which renders a new type of photodynanic inducers. The biological effects of these derivatives were assessed in HeLa and HCT116 human cancer cells. In particular, the tetra-glycofused structure 12 exhibited the highest cellular uptake and photocytotoxicity. Unlike the reported sugar-porphyrin conjugates, which normally localize in mitochondria or endoplasmic reticulum, the unique glycofused porphyrins in this study were dominantly localized in lysosomes. The measurement of the dual flurorescence of annexin V-FITC/PI by flow cytometry revealed that the cell death was caused by apoptosis. Further PARP cleavage study suggested that apoptosis induced by the treatment of compound 12 was via caspase-dependent apoptotic pathway in cancer cells.