Kinetics of the displacement of cyclobutane-1,1-dicarboxylate from diammine(cyclobutane-1,1-dicarboxylato)platinum(II) in aqueous solution

Canovese, Luciano; Cattalini, L.; Chessa, Gavino; Tobe, M. L.

doi:10.1039/dt9880002135

Cited by 75 publications

(58 citation statements)

References 2 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Carboplatin and oxaliplatin are significantly more stable to aquation, as expected because of the chelating nature of the leaving group ligand. Carboplatin is stable for up to 60 days in water [12], but direct substitution of one of the carboxylates by nucleobases is possible without the need for an aqua intermediate [13]. It has been proposed that carbonate can activate carboplatin [14], but this mechanism is not operative with cisplatin [15].…”

Section: (B) Aquation/activationmentioning

confidence: 99%

Third row transition metals for the treatment of cancer

Johnstone

Suntharalingam

Lippard

2015

Phil. Trans. R. Soc. A.

View full text Add to dashboard Cite

Platinum compounds are a mainstay of cancer chemotherapy, with over 50% of patients receiving platinum. But there is a great need for improvement. Major features of the cisplatin mechanism of action involve cancer cell entry, formation mainly of intrastrand cross-links that bend and unwind nuclear DNA, transcription inhibition and induction of cell-death programmes while evading repair. Recently, we discovered that platinum cross-link formation is not essential for activity. Monofunctional Pt compounds such as phenanthriplatin, which make only a single bond to DNA nucleobases, can be far more active and effective against a range of tumour types. Without a cross-link-induced bend, monofunctional complexes can be accommodated in the major groove of DNA. Their biological mechanism of action is similar to that of cisplatin. These discoveries opened the door to a large family of heavy metal-based drug candidates, including those of Os and Re, as will be described.

show abstract

Section: (B) Aquation/activationmentioning

confidence: 99%

Third row transition metals for the treatment of cancer

Johnstone

Suntharalingam

Lippard

2015

Phil. Trans. R. Soc. A.

View full text Add to dashboard Cite

show abstract

“…Hydrolysis of the oxalato complexes requires initial ring-opening, ligand displacement by chloride and subsequent conversion to the aquo and/or hydroxy species, thus requiring more time to bind with the DNA bases. 23,24 Cisplatin and carboplatin are more cytotoxic than the amphiphilic complexes, except when compared to carboplatin in A 549 cell line, against which six of the amphiphilic complexes were more cytotoxic.…”

Section: Cytotoxic Activitymentioning

confidence: 99%

Novel platinum(II) complexes of long chain aliphatic diamine ligands with oxalato as the leaving group: comparative cytotoxic activity relative to chloride precursors

Silva¹,

Barra²,

Rocha³

et al. 2010

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Os complexos de platina são importantes no desenvolvimento de drogas anticancerígenas. Sua citotoxicidade pode ser afetada pelos ligantes abandonadores, devido ao mecanismo da reação de hidrólise que ocorre antes da ligação do complexo ao DNA. Os grupos não-abandonadores, como as diaminas lipofílicas, também podem afetar a velocidade de entrada do composto na célula. Neste trabalho é descrita a síntese de novos complexos de platina(II) contendo ligantes oxalato e derivados de etilenodiamina N-substituída por uma cadeia carbônica longa de tamanho variável. Os produtos foram caracterizados por análise elementar, espectroscopia de absorção na região do infravermelho e ressonância magnética nuclear de 1 H, 13 C e 195 Pt. A atividade biológica dos complexos foi investigada em linhagens de células tumorais (A 549 , B16-F1, B16-F10, MDA-MB-231) e não-tumorais (BHK-21 e CHO). O tamanho da cadeia carbônica afetou a citotoxicidade e os complexos com oxalato mostraram-se menos citotóxicos do que os análogos com cloretos.Platinum complexes play an important role in the development of anticancer drugs. Their cytotoxicity can be influenced by the nature of the leaving ligands, due to the hydrolysis reaction that occurs prior to the binding of the platinum complex to DNA. Also, non-leaving groups such as lipophilic diamines may affect cellular uptake. In this work, we describe the synthesis of platinum(II) complexes having oxalato and long chain aliphatic N-alkyl ethylenediamines as ligands. The products were characterized by elemental analyses, infrared spectroscopy and 1 H, 13 C and 195 Pt NMR spectroscopy. Biological activity was assessed against tumor cell lines (A 549 , B16-F1, B16-F10, MDA-MB-231) and non-tumor cell lines (BHK-21 and CHO). The length of the carbon chain affects the cytotoxicity and the oxalato complexes were less cytotoxic than the respective chloride-containing analogues.

show abstract

“…These toxicity differences are likely attributable to the lower reactivity of carboplatin with nucleophiles, since the 1,1-cyclobutanedicarboxylic acid (CBDCA) ligand is a poorer leaving group than chloride. There are only a few previous studies on CBDCA ring-opening reactions of carboplatin (6)(7)(8) that report the relative inertness of carboplatin to hydrolysis and chloride substitution. For example, the half-life of carboplatin in chloride-free phosphate buffer at pH 7 and 37°C is 268 h compared with 24 h for cisplatin under identical conditions (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…There are only a few previous studies on CBDCA ring-opening reactions of carboplatin (6)(7)(8) that report the relative inertness of carboplatin to hydrolysis and chloride substitution. For example, the half-life of carboplatin in chloride-free phosphate buffer at pH 7 and 37°C is 268 h compared with 24 h for cisplatin under identical conditions (6)(7)(8). Both compounds predominantly interact with DNA at guanine and adenine nucleotides to form Pt-DNA monoadducts that frequently react with a second nucleotide to form Pt-DNA intra-and interstrand diadducts.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Carboplatin−DNA Binding in Genomic DNA and Bladder Cancer Cells As Determined by Accelerator Mass Spectrometry

Hah

Stivers

White

et al. 2006

Chem. Res. Toxicol.

101

View full text Add to dashboard Cite

Cisplatin and carboplatin are platinum-based drugs that are widely used in cancer chemotherapy. The cytotoxicity of these drugs is mediated by platinum-DNA monoadducts and intra-and interstrand diadducts, which are formed following uptake of the drug into the nucleus of cells. The pharmacodynamics of carboplatin display fewer side effects than for cisplatin, albeit with less potency, which may be due to differences in rates of DNA adduct formation. We report the use of accelerator mass spectrometry (AMS), a sensitive detection method often used for radiocarbon quantitation, to measure both the kinetics of [ 14 C]carboplatin-DNA adduct formation with genomic DNA and drug uptake and DNA binding in T24 human bladder cancer cells. Only carboplatin-DNA monoadducts contain radiocarbon in the platinated DNA, which allowed for calculation of kinetic rates and concentrations within the system. The percent of radiocarbon bound to salmon sperm DNA in the form of monoadducts was measured by AMS over 24 h. Knowledge of both the starting concentration of the parent carboplatin and the concentration of radiocarbon in the DNA at a variety of time points allowed calculation of the rates of Pt-DNA monoadduct formation and conversion to toxic cross-links. Importantly, the rate of carboplatin-DNA monoadduct formation was approximately 100-fold slower than that reported for the more potent cisplatin analogue, which may explain the lower toxicity of carboplatin. T24 human bladder cancer cells were incubated with a subpharmacological dose of [ 14 C]carboplatin, and the rate of accumulation of radiocarbon in the cells and nuclear DNA was measured by AMS. The lowest concentration of radiocarbon measured was approximately 1 amol/10 µg of DNA. This sensitivity may allow the method to be used for clinical applications.

show abstract

Kinetics of the displacement of cyclobutane-1,1-dicarboxylate from diammine(cyclobutane-1,1-dicarboxylato)platinum(II) in aqueous solution

Cited by 75 publications

References 2 publications

Third row transition metals for the treatment of cancer

Third row transition metals for the treatment of cancer

Novel platinum(II) complexes of long chain aliphatic diamine ligands with oxalato as the leaving group: comparative cytotoxic activity relative to chloride precursors

Kinetics of Carboplatin−DNA Binding in Genomic DNA and Bladder Cancer Cells As Determined by Accelerator Mass Spectrometry

Contact Info

Product

Resources

About