Tolyporphin macrocycles from the cyanobacterium Tolypothrix nodosa selectively bind copper and silver and reverse multidrug resistance

Prinsep, Michele R., Appleton, Trevor G., Hanson, Graeme R., Lane, Ian, Smith, Charles D., Puddick, Jonathan and Fairlie, David P. (2017) Tolyporphin macrocycles from the cyanobacterium Tolypothrix nodosa selectively bind copper and silver and reverse multidrug resistance. Inorganic Chemistry, 56 10: 5577-5585. doi:10.1021/acs.inorgchem.6b03000


Author Prinsep, Michele R.
Appleton, Trevor G.
Hanson, Graeme R.
Lane, Ian
Smith, Charles D.
Puddick, Jonathan
Fairlie, David P.
Title Tolyporphin macrocycles from the cyanobacterium Tolypothrix nodosa selectively bind copper and silver and reverse multidrug resistance
Formatted title
Tolyporphin macrocycles from the cyanobacterium Tolypothrix nodosa selectively bind copper and silver and reverse multidrug resistance
Journal name Inorganic Chemistry   Check publisher's open access policy
ISSN 1520-510X
0020-1669
Publication date 2017-05-15
Year available 2017
Sub-type Article (original research)
DOI 10.1021/acs.inorgchem.6b03000
Open Access Status Not yet assessed
Volume 56
Issue 10
Start page 5577
End page 5585
Total pages 9
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1606 Physical and Theoretical Chemistry
1604 Inorganic Chemistry
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 d -y 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.
Formatted 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.
Keyword Chemistry, Inorganic & Nuclear
Chemistry
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP0210330
CA 64983
1117017
Institutional Status UQ

 
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