Table of Contents
Metal-Based Drugs
Volume 3, Issue 2, Pages 85-89
http://dx.doi.org/10.1155/MBD.1996.85

Porphyrins and Metalloporphyrins: Potential Hypoxic Agents

1Dept. of Chemistry, University of British Columbia, Vancouver V6T 1Z1, Canada
2BC Cancer Research Centre, Vancouver V5Z 1L3, Canada

Received 13 February 1996; Accepted 24 February 1996

Copyright © 1996 Hindawi Publishing Corporation. 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.

Abstract

Synthetic water-soluble porphyrins and their metalloporphyrin derivatives with Co(III), Cu(II), Ru(II) and Pt(II), containing various functional groups within the meso-positions of the porphyrin, were synthesised and evaluated as hypoxic agents, especially as cytotoxins and radiosensitisers. Cobalt complexes of the porphyrins containing positively charged methylpyridinium groups showed selective toxicity toward hypoxic Chinese Hamster Ovary (CHO) cells. The Co(III) complexes of the cationic and the anionic porphyrins are all weak radiosensitisers toward hypoxic cells, the highest sensitisation enhancement ratio (SER = 1.22, at 50 μM) being with a porphyrin complex containing a cis-arrangement of two nitro and two methylpyridinium meso-substituents. A copper complex of a tetracationic porphyrin showed slight radiosensitisation activity with an SER value of about 1.1. The other metalloporphyrins showed no hypoxic selectivity or radiosensitisation activity. In total, over 50 porphyrin free bases have been synthesised, of which half are water-soluble and have been metallated; thus, the chemistry is now in place for further development of water-soluble hypoxic agents.