Synthesis, characterization, and cytotoxicity of the first oxaliplatin Pt(IV) derivative having a TSPO ligand in the axial position

Salvatore Savino, Nunzio Denora, Rosa Maria Iacobazzi, Letizia Porcelli, Amalia Azzariti, Giovanni Natile, Nicola Margiotta

Research output: Contribution to journalArticle

Abstract

The first Pt(IV) derivative of oxaliplatin carrying a ligand for TSPO (the 18-kDa mitochondrial translocator protein) has been developed. The expression of the translocator protein in the brain and liver of healthy humans is usually low, oppositely to steroid-synthesizing and rapidly proliferating tissues, where TSPO is much more abundant. The novel Pt(IV) complex, cis,trans,cis-[Pt(ethanedioato)Cl{2-(2-(4-(6,8-dichloro-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2- a]pyridin-2-yl)phenoxy)acetate)-ethanolato}(1R,2R-DACH)] (DACH = diaminocyclohexane), has been fully characterized by spectroscopic and spectrometric techniques and tested in vitro against human MCF7 breast carcinoma, U87 glioblastoma, and LoVo colon adenocarcinoma cell lines. In addition, affinity for TSPO (IC50 = 18.64 nM), cellular uptake (ca. 2 times greater than that of oxaliplatin in LoVo cancer cells, after 24 h treatment), and perturbation of cell cycle progression were investigated. Although the new compound was less active than oxaliplatin and did not exploit a synergistic proapoptotic effect due to the presence of the TSPO ligand, it appears to be promising in a receptor-mediated drug targeting context towards TSPO-overexpressing tumors, in particular colorectal cancer (IC50 = 2.31 µM after 72 h treatment).

Original languageEnglish
Article number1010
JournalInternational Journal of Molecular Sciences
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

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oxaliplatin
Cytotoxicity
cancer
Ligands
Cells
Derivatives
ligands
Inhibitory Concentration 50
synthesis
proteins
Proteins
steroids
Mitochondrial Proteins
Drug Delivery Systems
Glioblastoma
cultured cells
liver
progressions
breast
Liver

Keywords

  • Antitumor drugs
  • Colorectal cancer
  • Oxaliplatin
  • Platinum(IV)
  • Translocator protein 18 kDa
  • TSPO

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

Cite this

Synthesis, characterization, and cytotoxicity of the first oxaliplatin Pt(IV) derivative having a TSPO ligand in the axial position. / Savino, Salvatore; Denora, Nunzio; Iacobazzi, Rosa Maria; Porcelli, Letizia; Azzariti, Amalia; Natile, Giovanni; Margiotta, Nicola.

In: International Journal of Molecular Sciences, Vol. 17, No. 7, 1010, 01.07.2016.

Research output: Contribution to journalArticle

Savino, Salvatore ; Denora, Nunzio ; Iacobazzi, Rosa Maria ; Porcelli, Letizia ; Azzariti, Amalia ; Natile, Giovanni ; Margiotta, Nicola. / Synthesis, characterization, and cytotoxicity of the first oxaliplatin Pt(IV) derivative having a TSPO ligand in the axial position. In: International Journal of Molecular Sciences. 2016 ; Vol. 17, No. 7.
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