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

doi:10.1021/acs.inorgchem.6b03000

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 journal › Article › peer-review

18 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 d_x²-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 language	English (US)
Pages (from-to)	5577-5585
Number of pages	9
Journal	Inorganic chemistry
Volume	56
Issue number	10
DOIs	https://doi.org/10.1021/acs.inorgchem.6b03000
State	Published - May 15 2017

All Science Journal Classification (ASJC) codes

Physical and Theoretical Chemistry
Inorganic Chemistry

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10.1021/acs.inorgchem.6b03000

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@article{063ea23f57e745909e5c5cd589120e33,

title = "Tolyporphin Macrocycles from the Cyanobacterium Tolypothrix nodosa Selectively Bind Copper and Silver and Reverse Multidrug Resistance",

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.",

author = "Prinsep, {Mich{\`e}le R.} and Appleton, {Trevor G.} and Hanson, {Graeme R.} and Ian Lane and Smith, {Charles D.} and Jonathan Puddick and Fairlie, {David P.}",

note = "Funding Information: We thank the late R. E. Moore G. M. L. Patterson, and L. K. Larsen of Department of Chemistry, University of Hawaii, Honolulu, HI, for culturing T. nodosa A. Jones (IMB) and G. MacFarlane (Chemistry Department, The University of Queensland) for measuring the EI MS and FAB MS spectra, P. Gread (Chemistry Department, University of Waikato) for assistance with HRESI MS analyses, and L. R. Gahan (Chemistry Department, University of Queensland) for helpful discussion. The chemistry was funded through an Australian Research Council grant (DP0210330) and a Waikato Medical Research Foundation grant. Studies of the biological activities of the tolyporphins were supported by NIH Grant CA 64983. We thank the National Health and Medical Research Council for a Senior Principal Research Fellowship to D.P.F. (1117017). Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

year = "2017",

month = may,

day = "15",

doi = "10.1021/acs.inorgchem.6b03000",

language = "English (US)",

volume = "56",

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journal = "Inorganic chemistry",

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T1 - Tolyporphin Macrocycles from the Cyanobacterium Tolypothrix nodosa Selectively Bind Copper and Silver and Reverse Multidrug Resistance

AU - Prinsep, Michèle R.

AU - Appleton, Trevor G.

AU - Hanson, Graeme R.

AU - Lane, Ian

AU - Smith, Charles D.

AU - Puddick, Jonathan

AU - Fairlie, David P.

N1 - Funding Information: We thank the late R. E. Moore G. M. L. Patterson, and L. K. Larsen of Department of Chemistry, University of Hawaii, Honolulu, HI, for culturing T. nodosa A. Jones (IMB) and G. MacFarlane (Chemistry Department, The University of Queensland) for measuring the EI MS and FAB MS spectra, P. Gread (Chemistry Department, University of Waikato) for assistance with HRESI MS analyses, and L. R. Gahan (Chemistry Department, University of Queensland) for helpful discussion. The chemistry was funded through an Australian Research Council grant (DP0210330) and a Waikato Medical Research Foundation grant. Studies of the biological activities of the tolyporphins were supported by NIH Grant CA 64983. We thank the National Health and Medical Research Council for a Senior Principal Research Fellowship to D.P.F. (1117017). Publisher Copyright: © 2017 American Chemical Society.

PY - 2017/5/15

Y1 - 2017/5/15

N2 - 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.

AB - 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.

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JO - Inorganic chemistry

JF - Inorganic chemistry

IS - 10

ER -

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

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