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Int. J. Mol. Sci. 2016, 17(7), 1010; doi:10.3390/ijms17071010

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

1
Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy
2
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via E. Orabona 4, 70125 Bari, Italy
3
Istituto Tumori IRCCS Giovanni Paolo II, viale O. Flacco 65, 70124 Bari, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Nick Hadjiliadis
Received: 15 April 2016 / Revised: 17 May 2016 / Accepted: 20 June 2016 / Published: 25 June 2016
(This article belongs to the Special Issue Translocator Protein (TSPO))
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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). View Full-Text
Keywords: oxaliplatin; antitumor drugs; platinum(IV); translocator protein 18 kDa; TSPO; colorectal cancer oxaliplatin; antitumor drugs; platinum(IV); translocator protein 18 kDa; TSPO; colorectal cancer
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MDPI and ACS Style

Savino, S.; Denora, N.; Iacobazzi, R.M.; Porcelli, L.; Azzariti, A.; Natile, G.; Margiotta, N. Synthesis, Characterization, and Cytotoxicity of the First Oxaliplatin Pt(IV) Derivative Having a TSPO Ligand in the Axial Position. Int. J. Mol. Sci. 2016, 17, 1010.

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