Glycosylated porphyrin derivatives and their photodynamic activity in cancer cells

• Main Authors: Vedachalam, Seenuvasan, Choi, Bo-Hwa, Pasunooti, Kalyan Kumar, Ching, Kun Mei, Lee, Kijoon, Yoon, Ho Sup, Liu, Xue-Wei
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2012
• Subjects: DRNTU::Science::Biological sciences::Cytology
• Online Access: https://hdl.handle.net/10356/94433; http://hdl.handle.net/10220/7483
• Institution: Nanyang Technological University

The present study reports the design and synthesis of nine C2-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 D2-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.