Synthesis, Characterization, and Cytotoxicity of the First Oxaliplatin Pt(IV) Derivative Having a TSPO Ligand in the Axial Position

Autor: Amalia Azzariti, Salvatore Savino, Nunzio Denora, Nicola Margiotta, Giovanni Natile, Letizia Porcelli, Rosa Maria Iacobazzi
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Organoplatinum Compounds
Apoptosis
Ligands
01 natural sciences
lcsh:Chemistry
0302 clinical medicine
Cytotoxicity
lcsh:QH301-705.5
Spectroscopy
biology
Chemistry
Cell Cycle
General Medicine
Computer Science Applications
030220 oncology & carcinogenesis
MCF-7 Cells
TSPO
medicine.drug
Protein Binding
Stereochemistry
Antineoplastic Agents
colorectal cancer
010402 general chemistry
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Receptors
GABA
medicine
Translocator protein
Animals
Humans
Physical and Theoretical Chemistry
oxaliplatin
antitumor drugs
platinum(IV)
translocator protein 18 kDa
Molecular Biology
IC50
Organic Chemistry
Molecular biology
In vitro
0104 chemical sciences
Oxaliplatin
Rats
Targeted drug delivery
lcsh:Biology (General)
lcsh:QD1-999
Cell culture
Cancer cell
biology.protein
Zdroj: International Journal of Molecular Sciences; Volume 17; Issue 7; Pages: 1010
International Journal of Molecular Sciences, Vol 17, Iss 7, p 1010 (2016)
International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: 10.3390/ijms17071010
Popis: 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).
Databáze: OpenAIRE
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