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

Doris Hoefer, Hristo P. Varbanov (Korresp. Autor*in), Anton Legin, Michael A. Jakupec, Alexander Roller, Mathea Sophia Galanski, Bernhard K. Keppler

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

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.

OriginalspracheEnglisch
Seiten (von - bis)259-271
Seitenumfang13
FachzeitschriftJournal of Inorganic Biochemistry
Jahrgang153
DOIs
PublikationsstatusVeröffentlicht - Dez. 2015

ÖFOS 2012

  • 104003 Anorganische Chemie
  • 106002 Biochemie

Zitationsweisen