Non-hydrolysable glycosylated porphyrins and chlorins: Potential new photodynamic therapy agents and applications in vivo imaging

MEDI 99

Sebastian A. Thompson, sthompson@gc.cuny.edu1, Diana Samaroo, dsamaroo@hunter.cuny.edu2, Mikki Vinodu, mvinodu@hunter.cuny.edu2, and Charles Michael Drain, cdrain@hunter.cuny.edu3. (1) Department of Chemistry & Biochemistry, Hunter College and Graduate Center of the City University of New York, 695 Park Ave., New York, NY 10021, (2) Department of Chemistry, Hunter College of CUNY, 695 Park Ave, New York, NY 10021, (3) Department of Chemistry, Hunter College & Graduate Center of the City University of New York, 695 Park Ave, New York, NY 10021
A non hydrolysable tetra-S-glycosylated porphyrin (PGlu-4) is presented as a potential new photodynamic therapeutic (PDT). PGlu-4 does not hydrolyze under physiological condition, is selective taken up by a variety of cancer cells, and is mainly found to be bound to or in the mitochondria. Apoptosis or necroses are activated depending on the concentration of the macrocycle and the irradiation power. The components of the cell culture media (e.g. albumin, glucose) strongly effect uptake and degree of PGlu-4 aggregation. Interaction of PGlu-4 with proteins effect distribution and degree of aggregation inside the cell as well. Chlorin derivatives were made to increase the absorption in the red region of the spectra, but we find that these have ca. 5-fold increase fluorescence quantum yields, therefore these may serve as good fluorescence imaging agents. We observe chlorin fluorescence located at the mitochondria when cell are treated as little as 10 nM compound.
 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007