Impact of the equatorial coordination sphere on the rate of reduction, lipophilicity and cytotoxic activity of platinum(IV) complexes

Author(s)

Doris Hoefer, Hristo P. Varbanov, Michaela Hejl, Michael A. Jakupec, Alexander Roller, Mathea Sophia Galanski, Bernhard K. Keppler

Abstract

The impact of the equatorial coordination sphere on the reduction behavior (i.e. rate of reduction) of platinum(IV) complexes with axial carboxylato ligands was studied. Moreover, the influence of equatorial ligands on the stability, lipophilicity and cytotoxicity of platinum(IV) compounds was evaluated. For this purpose, a series of platinum(IV) complexes featuring axial carboxylato ligands (succinic acid monoesters) was synthesized; anionic carboxylato (OAc

⁻, oxalate) and halido (Cl

⁻, Br

⁻, I

⁻) ligands served as leaving groups and am(m)ine carrier ligands were provided by monodentately (isopropylamine, ammine + cyclohexaneamine) or bidentately (ethane-1,2-diamine) coordinating am(m)ines. All platinum(IV) products were fully characterized based on elemental analysis, high resolution mass spectrometry and multinuclear (

¹H,

¹³C,

¹⁵N,

¹⁹⁵Pt) NMR spectroscopy as well as by X-ray diffraction in some cases. The rate of reduction in the presence of ascorbic acid was determined by NMR spectroscopy and the lipophilicity of the complexes was investigated by analytical reversed phase HPLC measurements. Cytotoxic properties were studied by means of a colorimetric microculture assay in three human cancer cell lines derived from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1) as well as cisplatin insensitive colon carcinoma (SW480) and non-small cell lung cancer (A549).

Organisation(s)

Department of Inorganic Chemistry, Core Facility Crystal Structure Analysis, NMR Centre

Journal

Journal of Inorganic Biochemistry

Volume

174

Pages

119-129

No. of pages

11

ISSN

0162-0134

DOI

https://doi.org/10.1016/j.jinorgbio.2017.06.005

Publication date

09-2017

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry, 301904 Cancer research, 106002 Biochemistry

Keywords

ASJC Scopus subject areas

Biochemistry, Inorganic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/09ba2a30-1848-49f0-ac90-b9d290e63e9e