Novel Endothall‐Containing Platinum(IV) Complexes: Synthesis, Characterization, and Cytotoxic Activity

Reithofer, Michael R.; Valiahdi, Seied Mojtaba; Galanski, Markus; Jakupec, Michael A.; Arion, Vladimir B.; Keppler, Bernhard K.

doi:10.1002/cbdv.200890197

Cited by 39 publications

(35 citation statements)

References 30 publications

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“…Such is the case for canthaplatin (Chart 23B), 478 a cisplatin prodrug in which the axial ligands are derivatives of the protein phosphatase 2A inhibitor demethylcantharidin. 479 The Boc-protected pipirazinyl groups on the axial canthaplatin-derived ligands allow the prodrug to be readily encapsulated in PLGA-PEG nanoparticles affording a construct that is taken up via endocytosis, decreases the efficiency of DNA repair by inhibiting protein phosphatase 2A, and releases cisplatin. The enhancement of the efficacy of the cisplatin as a result of the inhibited DNA repair was confirmed in vitro and in vivo with a mouse xenograft model of lung cancer.…”

Section: Nanodelivery Of Platinum(iv) Complexesmentioning

confidence: 99%

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

2016

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The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer,, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing non-classical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore non-classical platinum(II) complexes with trans geometry and with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-treat agents, and photoactivatable platinum(IV) complexes. Nanodelivery particles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also reflect our optimism that the next generation of platinum cancer drugs is about to arrive.

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Section: Nanodelivery Of Platinum(iv) Complexesmentioning

confidence: 99%

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

2016

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“…Lippard tethered various bioactive peptides to Pt(IV) complexes to target angiogenic tumors [51] and Keppler attached cantharidins that belong to a class of established traditional Chinese medicine agents, to Pt(IV) [52]. Pt(IV) complexes were attached to macromolecules that are in widespread use as drug carriers.…”

Section: Platinum(iv) Complexes With Bioactive Ligandsmentioning

confidence: 99%

What do we know about the reduction of Pt(IV) pro-drugs?

Wexselblatt

Gibson

2012

Journal of Inorganic Biochemistry

321

320

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“…By varying the two axial ligands, one can predictably alter the redox potential17–19 and lipophilicity20–22 of the platinum(IV) complex while leaving the DNA binding cis -diammineplatinum moiety unaltered. Furthermore, the axial coordination sites can serve as binding sites for other biologically active ligands, which may have synergistic effects with platinum therapy, as demonstrated by us23–25 and by others 26, 27. The ability to tether platinum(IV) complexes via the axial ligands to various nano-delivery devices for increased cellular uptake and selectivity28–35 is another advantage.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Cytotoxicity of Platinum(IV) Carbamate Complexes

Wilson¹,

Lippard²

2011

Inorg. Chem.

107

119

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The synthesis, characterization, and cytotoxicity of eight new platinum(IV) complexes having the general formula, c,c,t-[Pt(NH3)2Cl2(O2CNHR)2], are reported, where R = tert-butyl (4), cyclopentyl (5), cyclohexyl (6), phenyl (7), p-tolyl (8), p-anisole (9), 4-fluorophenyl (10), or 1-naphthyl (11). These compounds were synthesized by reacting organic isocyanates with the platinum(IV) complex, c,c,t-[Pt(NH3)2Cl2(OH)2]. The electrochemistry of the compounds was investigated by cyclic voltammetry. The aryl carbamate complexes 7 – 11 exhibit reduction peak potentials near −720 mV vs. Ag/AgCl, whereas the alkyl carbamate complexes display reduction peak potentials between −820 and −850 mV vs. Ag/AgCl. The cyclic voltammograms of c,c,t-[Pt(NH3)2Cl2(O2CCH3)2] (1), c,c,t-[Pt(NH3)2Cl2(O2CCF3)2] (2), and cis-[Pt(NH3)2Cl4] (3) were measured for comparison. Density functional theory (DFT) studies were undertaken to investigate the electronic structures of 1 – 11 and to determine their adiabatic electron affinities. A linear correlation (R2 = 0.887) between computed adiabatic electron affinities and measured reduction peak potential was discovered. The biological activity of 4 – 11 and, for comparison, cisplatin was evaluated in human lung cancer A549 and normal MRC-5 cells by the MTT assay. The compounds exhibit comparable or slightly better activity than cisplatin against the A549 cells. In MRC-5 cells, all are equally or slightly less cytotoxic than cisplatin, except for 4 and 5, which are more toxic.

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Novel Endothall‐Containing Platinum(IV) Complexes: Synthesis, Characterization, and Cytotoxic Activity

Cited by 39 publications

References 30 publications

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

What do we know about the reduction of Pt(IV) pro-drugs?

Synthesis, Characterization, and Cytotoxicity of Platinum(IV) Carbamate Complexes

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