DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex

Thaylan Pinheiro Araujo, Valentina Gandin, Paul Kavanagh, Jeremy Phillip Braude, Luca Nodari, Diego Montagner*, Andrea Erxleben

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A novel bimetallic Fe(III) complex with the bis(triaza-cyclononane) ligand 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol (bcmp) is reported. [Fe2{bcmp(-H)}(μ-OH)Cl2]Cl2 (2) contains two octahedral Fe(III) centers bound to the two triaza-cyclononane rings of bcmp. The coordination sphere is completed by one chlorine, one bridging phenolate oxygen and one bridging hydroxide group. The complex has been characterized by elemental analysis, Mössbauer spectroscopy, UV–Vis spectroscopy, pH potentiometric titration, ESI mass spectrometry and cyclic voltammetry. The complex hydrolyzes the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) with a maximum activity a pH 7. Michaelis–Menten behavior is observed with kcat = 3.56 × 10−4 s−1 and Km = 0.56 mM (pH 7.0, 40 °C). The interaction of 2 with CT DNA was studied by electronic absorption spectroscopy and gel electrophoresis. Notably, the complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration (10 μM) in the presence of an external reducing agent (ascorbic acid). Finally, the in vitro antiproliferative activity of 2 was assessed on a panel of human cancer cell lines and results revealed that the complex exhibited a significant cytotoxic effects in particular versus colon LoVo cancer cells, wih IC50 value 2.5 times lower than that shown by the reference metallodrug cisplatin (3.54 versus 8.53 μM).

Original languageEnglish
Pages (from-to)170-175
Number of pages6
JournalInorganica Chimica Acta
Volume452
Early online date03 Mar 2016
DOIs
Publication statusPublished - 01 Oct 2016

Fingerprint

Cytotoxicity
cleavage
DNA
deoxyribonucleic acid
cancer
Cells
Spectroscopy
ascorbic acid
Ascorbic acid
Chlorine
Reducing Agents
Reducing agents
electrophoresis
Electrophoresis
Titration
Absorption spectroscopy
cultured cells
titration
spectroscopy
Cisplatin

Keywords

  • Cytotoxicity
  • DNA binding
  • DNA cleavage
  • Iron(III)

Cite this

Pinheiro Araujo, T., Gandin, V., Kavanagh, P., Braude, J. P., Nodari, L., Montagner, D., & Erxleben, A. (2016). DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex. Inorganica Chimica Acta, 452, 170-175. https://doi.org/10.1016/j.ica.2016.02.044
Pinheiro Araujo, Thaylan ; Gandin, Valentina ; Kavanagh, Paul ; Braude, Jeremy Phillip ; Nodari, Luca ; Montagner, Diego ; Erxleben, Andrea. / DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex. In: Inorganica Chimica Acta. 2016 ; Vol. 452. pp. 170-175.
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abstract = "A novel bimetallic Fe(III) complex with the bis(triaza-cyclononane) ligand 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol (bcmp) is reported. [Fe2{bcmp(-H)}(μ-OH)Cl2]Cl2 (2) contains two octahedral Fe(III) centers bound to the two triaza-cyclononane rings of bcmp. The coordination sphere is completed by one chlorine, one bridging phenolate oxygen and one bridging hydroxide group. The complex has been characterized by elemental analysis, M{\"o}ssbauer spectroscopy, UV–Vis spectroscopy, pH potentiometric titration, ESI mass spectrometry and cyclic voltammetry. The complex hydrolyzes the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) with a maximum activity a pH 7. Michaelis–Menten behavior is observed with kcat = 3.56 × 10−4 s−1 and Km = 0.56 mM (pH 7.0, 40 °C). The interaction of 2 with CT DNA was studied by electronic absorption spectroscopy and gel electrophoresis. Notably, the complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration (10 μM) in the presence of an external reducing agent (ascorbic acid). Finally, the in vitro antiproliferative activity of 2 was assessed on a panel of human cancer cell lines and results revealed that the complex exhibited a significant cytotoxic effects in particular versus colon LoVo cancer cells, wih IC50 value 2.5 times lower than that shown by the reference metallodrug cisplatin (3.54 versus 8.53 μM).",
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Pinheiro Araujo, T, Gandin, V, Kavanagh, P, Braude, JP, Nodari, L, Montagner, D & Erxleben, A 2016, 'DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex', Inorganica Chimica Acta, vol. 452, pp. 170-175. https://doi.org/10.1016/j.ica.2016.02.044

DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex. / Pinheiro Araujo, Thaylan; Gandin, Valentina; Kavanagh, Paul; Braude, Jeremy Phillip; Nodari, Luca; Montagner, Diego; Erxleben, Andrea.

In: Inorganica Chimica Acta, Vol. 452, 01.10.2016, p. 170-175.

Research output: Contribution to journalArticle

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T1 - DNA binding, cleavage and cytotoxicity of a novel dimetallic Fe(III) triaza-cyclononane complex

AU - Pinheiro Araujo, Thaylan

AU - Gandin, Valentina

AU - Kavanagh, Paul

AU - Braude, Jeremy Phillip

AU - Nodari, Luca

AU - Montagner, Diego

AU - Erxleben, Andrea

PY - 2016/10/1

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N2 - A novel bimetallic Fe(III) complex with the bis(triaza-cyclononane) ligand 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol (bcmp) is reported. [Fe2{bcmp(-H)}(μ-OH)Cl2]Cl2 (2) contains two octahedral Fe(III) centers bound to the two triaza-cyclononane rings of bcmp. The coordination sphere is completed by one chlorine, one bridging phenolate oxygen and one bridging hydroxide group. The complex has been characterized by elemental analysis, Mössbauer spectroscopy, UV–Vis spectroscopy, pH potentiometric titration, ESI mass spectrometry and cyclic voltammetry. The complex hydrolyzes the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) with a maximum activity a pH 7. Michaelis–Menten behavior is observed with kcat = 3.56 × 10−4 s−1 and Km = 0.56 mM (pH 7.0, 40 °C). The interaction of 2 with CT DNA was studied by electronic absorption spectroscopy and gel electrophoresis. Notably, the complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration (10 μM) in the presence of an external reducing agent (ascorbic acid). Finally, the in vitro antiproliferative activity of 2 was assessed on a panel of human cancer cell lines and results revealed that the complex exhibited a significant cytotoxic effects in particular versus colon LoVo cancer cells, wih IC50 value 2.5 times lower than that shown by the reference metallodrug cisplatin (3.54 versus 8.53 μM).

AB - A novel bimetallic Fe(III) complex with the bis(triaza-cyclononane) ligand 2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol (bcmp) is reported. [Fe2{bcmp(-H)}(μ-OH)Cl2]Cl2 (2) contains two octahedral Fe(III) centers bound to the two triaza-cyclononane rings of bcmp. The coordination sphere is completed by one chlorine, one bridging phenolate oxygen and one bridging hydroxide group. The complex has been characterized by elemental analysis, Mössbauer spectroscopy, UV–Vis spectroscopy, pH potentiometric titration, ESI mass spectrometry and cyclic voltammetry. The complex hydrolyzes the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) with a maximum activity a pH 7. Michaelis–Menten behavior is observed with kcat = 3.56 × 10−4 s−1 and Km = 0.56 mM (pH 7.0, 40 °C). The interaction of 2 with CT DNA was studied by electronic absorption spectroscopy and gel electrophoresis. Notably, the complex relaxes supercoiled pUC19 DNA into the nicked form at low micromolar concentration (10 μM) in the presence of an external reducing agent (ascorbic acid). Finally, the in vitro antiproliferative activity of 2 was assessed on a panel of human cancer cell lines and results revealed that the complex exhibited a significant cytotoxic effects in particular versus colon LoVo cancer cells, wih IC50 value 2.5 times lower than that shown by the reference metallodrug cisplatin (3.54 versus 8.53 μM).

KW - Cytotoxicity

KW - DNA binding

KW - DNA cleavage

KW - Iron(III)

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