Table of Contents
Metal-Based Drugs
Volume 2008, Article ID 391418, 13 pages
Research Article

Synthesis and Biological Analysis of Thiotetra(ethylene glycol) monomethyl Ether-Functionalized Porphyrazines: Cellular Uptake and Toxicity Studies

1Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
2Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Chicago, IL 60612, USA
3Jesse Brown VAMC, 820 South Damen Avenue, Chicago, IL 60612, USA
4Department of Chemistry, Faculty of Natural Sciences, Imperial College London, Faculty Building, South Kensington Campus, London SW7 2AZ, UK

Received 29 May 2007; Revised 20 July 2007; Accepted 6 August 2007

Academic Editor: Michael J. Cook

Copyright © 2008 Sangwan Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The porphyrazines (pzs), a class of porphyrin analogues, are being investigated for their potential use as tumor imaging/therapeutic agents. We here examine six peripherally-functionalized M[pz(AnB4-n)] pzs with n=4, 3, or 2 (in a trans conformation) and M = H2 or Zn, where A is an [S((CH2)2O)4Me]2 unit and B is a fused β,β-diisopropyloxybenzo group. Cell viability/proliferation assays and fluorescence microscopy were carried out in both tumor and normal cells. Dark toxicity studies disclosed that four of the compounds exhibited toxicity in both normal and tumor cells; one was nontoxic in both normal and tumor cells, and one was selectively toxic to normal cells. Additionally, three of the pzs showed enhanced photo-induced toxicity with these effects in some cases being observed at treatment concentrations of up to ten-fold lower than that needed for a response in Photofrin. All six compounds were preferentially absorbed by tumor cells, suggesting that they have potential as in vitro diagnostic agents and as aids in the isolation and purification of aberrant cells from pathological specimens. In particular, two promising diagnostic candidates have been identified as part of this work.