Developing a structure-function relationship for anionic porphyrazines exhibiting selective anti-tumor activity

Benjamin J. Vesper, Sangwan Lee, Neal D. Hammer, Kim M. Elseth, Anthony G.M. Barrett, Brian M. Hoffman, James A. Radosevich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The porphyrazines (pzs) are a class of porphyrin derivatives being studied for their use as optical imaging agents and photodynamic therapy (PDT) anti-tumor agents. A previous study revealed that the anionic pz, 18 - of the form H2[pz(An;B4-n)], where A is [S(CH2)3CO2-], B is a fused β′,β′-diisopropyloxy benzo group, with n = 2 (trans)-selectively killed tumor cells, while analogous neutral and positively charged pzs lacked this property. In this report, we compare the properties of a suite of three H2 [pz(An;B4-n)] pzs containing the same A and B groups as 18, but differing in their values of n: pzs 4 (n = 4) and 11 (n = 3), and 18 (n = 2, trans) exhibit a progressive variation in charge due to the carboxylates, balance between hydrophobic/hydrophilic character, as well as a progressive variation in the singlet oxygen quantum yield (ΦΔ): ΦΔ (18) > ΦΔ (11) > φΔ (4). The biological activity of the pzs was tested in human lung carcinoma (A549) and SV40 transformed embryonic (WI-38 VA13) cell lines. Pzs 4 and 11 exhibited significant toxicity in both tumor and normal cells, while 18 showed selective anti-tumor cell activity in a dose-dependent manner. As the number of net negative charges decreased, the compounds became less toxic to normal cells, and the killing effect observed with these compounds was light independent. These observations indicate that the toxicity may have little to do with singlet oxygen quantum yields, but rather is more dependent on the net number of negative charges a pz contains. The study reported herein presents an example of how the porphyrazines can be easily modified to vary their biological behavior and specifically suggest that anionic porphyrazines pzs with lower n (fewer carboxylates, larger hydrophobic core) are more specific tumor killers, while those with larger n (increased net negative charge) are more potent tumor killers.

Original languageEnglish (US)
Pages (from-to)180-186
Number of pages7
JournalJournal of Photochemistry and Photobiology B: Biology
Issue number3
StatePublished - Mar 1 2006


  • Anionic
  • Anti-tumor
  • Photodynamic therapy
  • Porphyrazine
  • Proliferation
  • Tetraazaporphyrin

ASJC Scopus subject areas

  • Radiation
  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging


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