Is antitumor Pt(IV) complex containing two axial lonidamine ligands a true dual- or multi-action prodrug?
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
35759404
DOI
10.1093/mtomcs/mfac048
PII: 6618656
Knihovny.cz E-resources
- Keywords
- bioinorganic chemistry, lonidamine, medicinal inorganic chemistry, metals in medicine, Pt(IV) complexes,
- MeSH
- Antineoplastic Agents * pharmacology MeSH
- Indazoles MeSH
- Ligands MeSH
- Cell Line, Tumor MeSH
- Prodrugs * pharmacology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antineoplastic Agents * MeSH
- Indazoles MeSH
- Ligands MeSH
- lonidamine MeSH Browser
- Prodrugs * MeSH
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.
Blokhin Cancer Center Russian Academy of Medical Sciences 115478 Moscow Russian Federation
Czech Academy of Sciences Institute of Biophysics Brno CZ 61265 Czech Republic
Department of Chemistry City University of Hong Kong Hong Kong SAR P R China
Faculty of Chemistry Lomonosov Moscow State University 119991 Moscow Russian Federation
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