Improved reaction conditions for the synthesis of new NKP-1339 derivatives and preliminary investigations on their anticancer potential

P. -S. Kuhn; V. Pichler; A. Roller; M. Hejl; M. A. Jakupec; W. Kandioller; B. K. Keppler

doi:10.1039/c4dt01645a

Improved reaction conditions for the synthesis of new NKP-1339 derivatives and preliminary investigations on their anticancer potential

P. -S. Kuhn
, V. Pichler
, A. Roller
, M. Hejl
, M. A. Jakupec
, W. Kandioller (Corresponding author)
, B. K. Keppler

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

The very promising results of Na-trans-[RuCl ₄(1H-indazole) ₂] (NKP-1339) in clinical studies have fuelled renewed interest in the research and development of ruthenium(iii) coordination compounds for cancer therapy. By applying an improved synthetic approach to this class of coordination compounds, six new examples of the general formula (cation)-trans-[RuCl ₄(azole) ₂], where (cation) = tetrabutylammonium (Bu ₄N) ⁺ (1, 2), sodium (3, 4), azolium (5, 6), and azole = 1-methyl-indazole (1, 3, 5), 1-ethyl-indazole (2, 4, 6), have been prepared. All compounds have been characterized by elemental analysis, electrospray ionization (ESI) mass spectrometry, UV-vis-, and NMR-spectroscopy and, if possible, X-ray diffraction analysis. Furthermore, the influence of the alkyl substituent at the position N1 of the indazole backbone on the stability in aqueous media as well as on the biological activity in three human cancer cell lines (CH1, A549, and SW480) and on the cellular accumulation in SW480 cells is discussed. This journal is

Original language	English
Pages (from-to)	659-668
Number of pages	10
Journal	Dalton Transactions
Volume	44
Issue number	2
DOIs	https://doi.org/10.1039/c4dt01645a
Publication status	Published - 2015

Funding

We thank Prof. Vladimir Arion for the refinement of the X-ray diffraction data, Dr. Samuel Meier for ESI-MS experiments and the University of Vienna for financial support.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Austrian Fields of Science 2012

104003 Inorganic chemistry
301904 Cancer research

Keywords

IN-VITRO
RUTHENIUM(III) COMPLEX
CRYSTAL-STRUCTURE
DRUGS
ANTITUMOR
IMIDAZOLE
INDAZOLE
DESIGN
CELLS

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10.1039/c4dt01645a

Cite this

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abstract = "The very promising results of Na-trans-[RuCl 4(1H-indazole) 2] (NKP-1339) in clinical studies have fuelled renewed interest in the research and development of ruthenium(iii) coordination compounds for cancer therapy. By applying an improved synthetic approach to this class of coordination compounds, six new examples of the general formula (cation)-trans-[RuCl 4(azole) 2], where (cation) = tetrabutylammonium (Bu 4N) + (1, 2), sodium (3, 4), azolium (5, 6), and azole = 1-methyl-indazole (1, 3, 5), 1-ethyl-indazole (2, 4, 6), have been prepared. All compounds have been characterized by elemental analysis, electrospray ionization (ESI) mass spectrometry, UV-vis-, and NMR-spectroscopy and, if possible, X-ray diffraction analysis. Furthermore, the influence of the alkyl substituent at the position N1 of the indazole backbone on the stability in aqueous media as well as on the biological activity in three human cancer cell lines (CH1, A549, and SW480) and on the cellular accumulation in SW480 cells is discussed. This journal is ",

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language = "English",

volume = "44",

pages = "659--668",

journal = "Dalton Transactions",

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T1 - Improved reaction conditions for the synthesis of new NKP-1339 derivatives and preliminary investigations on their anticancer potential

AU - Kuhn, P. -S.

AU - Pichler, V.

AU - Roller, A.

AU - Hejl, M.

AU - Jakupec, M. A.

AU - Kandioller, W.

AU - Keppler, B. K.

N1 - Publisher Copyright: © The Royal Society of Chemistry.

PY - 2015

Y1 - 2015

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AB - The very promising results of Na-trans-[RuCl 4(1H-indazole) 2] (NKP-1339) in clinical studies have fuelled renewed interest in the research and development of ruthenium(iii) coordination compounds for cancer therapy. By applying an improved synthetic approach to this class of coordination compounds, six new examples of the general formula (cation)-trans-[RuCl 4(azole) 2], where (cation) = tetrabutylammonium (Bu 4N) + (1, 2), sodium (3, 4), azolium (5, 6), and azole = 1-methyl-indazole (1, 3, 5), 1-ethyl-indazole (2, 4, 6), have been prepared. All compounds have been characterized by elemental analysis, electrospray ionization (ESI) mass spectrometry, UV-vis-, and NMR-spectroscopy and, if possible, X-ray diffraction analysis. Furthermore, the influence of the alkyl substituent at the position N1 of the indazole backbone on the stability in aqueous media as well as on the biological activity in three human cancer cell lines (CH1, A549, and SW480) and on the cellular accumulation in SW480 cells is discussed. This journal is

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KW - RUTHENIUM(III) COMPLEX

KW - CRYSTAL-STRUCTURE

KW - DRUGS

KW - ANTITUMOR

KW - IMIDAZOLE

KW - INDAZOLE

KW - DESIGN

KW - CELLS

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IS - 2

ER -

Improved reaction conditions for the synthesis of new NKP-1339 derivatives and preliminary investigations on their anticancer potential

Abstract

Funding

UN SDGs

Austrian Fields of Science 2012

Keywords

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