Antiproliferative activity of a series of cisplatin-based Pt(IV)-acetylamido/carboxylato prodrugs

Dalton Transactions : an International Journal of Inorganic Chemistry
Mauro RaveraDomenico Osella

Abstract

We report studies of a novel series of Pt(IV) complexes exhibiting an asymmetric combination of acetylamido and carboxylato ligands in the axial positions. We demonstrate efficient synthesis of a series of analogues, differing in the alkyl chain length and hence lipophilicity, from a stable acetylamido/hydroxido complex formed by reaction of cisplatin with peroxyacetimidic acid (PAIA). NMR spectroscopy and X-ray crystallography confirm the identity of the resulting complexes, and highlight subtle differences in the structure and stability of acetylamido complexes compared to the equivalent acetato complexes. Reduction of acetylamido complexes, whether achieved chemically or electro-chemically, is significantly more difficult than that of acetate complexes, resulting in lower antiproliferative activity for shorter-chain complexes. For those with longer chains and hence greater cell uptake, this difference is negated and acetylamido complexes are as active as acetato analogues, both exhibiting antiproliferative potency (1/IC50) against A2780 ovarian cancer cells similar to that of cisplatin.

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Citations

Oct 7, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Elisabetta GabanoDomenico Osella
Nov 2, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·M RaveraD Osella
Jun 13, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Elisabetta GabanoDomenico Osella
Oct 20, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Dariusz Smiłowicz, Nils Metzler-Nolte
Apr 17, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Davide CorintiDomenico Osella
Jul 25, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·E GabanoM Ravera
Feb 18, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Mauro RaveraDomenico Osella
Nov 30, 2016·Journal of Inorganic Biochemistry·Mauro RaveraDomenico Osella
Apr 14, 2019·Journal of the American Society for Mass Spectrometry·Davide CorintiDomenico Osella
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elisabetta GabanoMauro Ravera
Sep 15, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Houzong YaoGuangyu Zhu
Jan 12, 2022·Dalton Transactions : an International Journal of Inorganic Chemistry·Mauro RaveraDomenico Osella

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