Tetracarboxylatoplatinum(IV) complexes featuring monodentate leaving groups - A rational approach toward exploiting the platinum(IV) prodrug strategy

Author(s)

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

Abstract

A series of novel symmetrically and unsymmetrically coordinated platinum(IV) complexes with monodentate carboxylato ligands was synthesized. The compounds exhibit a general coordination sphere of [Pt(en)(OCOR)

₂(OCOR′)(OCOR″], where the carboxylato ligands are represented by acetato and succinic acid monoester ligands. Dicarboxylatoplatinum(II) complexes were synthesized and oxidized symmetrically or unsymmetrically to obtain platinum(IV) complexes, which were subsequently carboxylated with noncyclic anhydrides. The compounds were investigated in detail by elemental analysis, mass spectrometry, infrared and multinuclear (

¹H,

¹³C,

¹⁵N,

¹⁹⁵Pt) NMR spectroscopy as well as by X-ray diffraction in some cases. The reduction behavior was followed by NMR spectroscopy, while stability and lipophilicity were examined by analytical reversed phase HPLC measurements. Cytotoxic properties were studied in three human cancer cell lines derived from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1), cisplatin insensitive colon carcinoma (SW480) and non-small cell lung cancer (A549). Thereby, the most lipophilic (yet water soluble) platinum(IV) complexes showed promising IC

₅₀ values in the low micromolar and even nanomolar range, demonstrating the significant advantage of using equatorially coordinated monodentate carboxylato ligands.

Organisation(s)

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

External organisation(s)

École polytechnique fédérale de Lausanne

Journal

Journal of Inorganic Biochemistry

Volume

153

Pages

259-271

No. of pages

13

ISSN

0162-0134

DOI

https://doi.org/10.1016/j.jinorgbio.2015.08.018

Publication date

12-2015

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry, 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/aced0882-1583-47bc-8238-89fed077cf36