Is antitumor Pt(IV) complex containing two axial lonidamine ligands a true dual- or multi-action prodrug?

Jana Kasparkova; Hana Kostrhunova; Vojtech Novohradsky; Lili Ma; Guangyu Zhu; Elena R Milaeva; Alexender A Shtill; Robin Vinck; Gilles Gasser; Viktor Brabec; Alexey A Nazarov

doi:10.1093/mtomcs/mfac048

Is antitumor Pt(IV) complex containing two axial lonidamine ligands a true dual- or multi-action prodrug?

Jana Kasparkova, Hana Kostrhunova, Vojtech Novohradsky, Lili Ma, Guangyu Zhu, Elena R Milaeva, Alexender A Shtill, Robin Vinck, Gilles Gasser, Viktor Brabec^*, Alexey A Nazarov^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

7 Citations (Scopus)

Abstract

This work studied the mechanism of action of a Pt(IV) complex 2 bearing two axial lonidamine ligands, which are selective inhibitors of aerobic glycolysis. The presence of two lonidamine ligands in 2 compared to the parent Pt(II) complex increased its antiproliferative activity, cellular accumulation, and changed its cell cycle profile and mechanism of cell death. In 3D cell culture, 2 showed exceptional antiproliferative activity with IC₅₀ values as low as 1.6 μM in MCF7 cells. The study on the influence of the lonidamine ligands in the Pt complex on glycolysis showed only low potency of ligands to affect metabolic processes in cancer cells, making the investigated complex, not a dual- or multi-action prodrug. However, the Pt(IV) prodrug effectively delivers the cytotoxic Pt(II) complex into cancer cells.

Original language	English
Article number	mfac048
Journal	Metallomics
Volume	14
Issue number	7
Online published	27 Jun 2022
DOIs	https://doi.org/10.1093/mtomcs/mfac048
Publication status	Published - Jul 2022

Research Keywords

bioinorganic chemistry
lonidamine
medicinal inorganic chemistry, metals in medicine, Pt(IV) complexes

UN SDGs

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

Access Output

10.1093/mtomcs/mfac048

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

@article{4123103598c1489588417e881ce5572b,

title = "Is antitumor Pt(IV) complex containing two axial lonidamine ligands a true dual- or multi-action prodrug?",

abstract = "This work studied the mechanism of action of a Pt(IV) complex 2 bearing two axial lonidamine ligands, which are selective inhibitors of aerobic glycolysis. The presence of two lonidamine ligands in 2 compared to the parent Pt(II) complex increased its antiproliferative activity, cellular accumulation, and changed its cell cycle profile and mechanism of cell death. In 3D cell culture, 2 showed exceptional antiproliferative activity with IC50 values as low as 1.6 μM in MCF7 cells. The study on the influence of the lonidamine ligands in the Pt complex on glycolysis showed only low potency of ligands to affect metabolic processes in cancer cells, making the investigated complex, not a dual- or multi-action prodrug. However, the Pt(IV) prodrug effectively delivers the cytotoxic Pt(II) complex into cancer cells.",

keywords = "bioinorganic chemistry, lonidamine, medicinal inorganic chemistry, metals in medicine, Pt(IV) complexes",

author = "Jana Kasparkova and Hana Kostrhunova and Vojtech Novohradsky and Lili Ma and Guangyu Zhu and Milaeva, {Elena R} and Shtill, {Alexender A} and Robin Vinck and Gilles Gasser and Viktor Brabec and Nazarov, {Alexey A}",

year = "2022",

month = jul,

doi = "10.1093/mtomcs/mfac048",

language = "English",

volume = "14",

journal = "Metallomics",

issn = "1756-591X",