Tolyporphin Macrocycles from the Cyanobacterium Tolypothrix nodosa Selectively Bind Copper and Silver and Reverse Multidrug Resistance

Michèle R. Prinsep, Trevor G. Appleton, Graeme R. Hanson, Ian Lane, Charles D. Smith, Jonathan Puddick, David P. Fairlie

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Tolyporphins are glycosylated macrocycles isolated from lipophilic soil extracts of the cyanobacterium, Tolypothrix nodosa, and found to potentiate the cytotoxicity of antitumor drugs like vinblastine and adriamycin. Here we find that, unlike porphyrins, tolyporphins are not able to form complexes with most metal ions. However, they do react strongly with copper(II) and silver(II), forming square-planar metal complexes with an unpaired electron in a dx2-y2 orbital of the metal delocalized onto the ligating tolyporphin nitrogen atoms. Complexes were characterized by visible absorption spectra, mass spectrometry (EI, FAB, ESI, LDI-TOF, and MALDI-TOF) and multifrequency continuous-wave electron paramagnetic resonance spectra. Copper(II) and silver(II) complexes of tolyporphins A and E were found to have the interesting property of reversing multidrug resistance (MDR), with the copper complexes being less toxic than free tolyporphins. Reactive oxygen-free radicals were implicated in both the cytotoxic and MDR-reversing effects of free and metalated tolyporphins.

Original languageEnglish (US)
Pages (from-to)5577-5585
Number of pages9
JournalInorganic chemistry
Volume56
Issue number10
DOIs
StatePublished - May 15 2017

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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