Synthesis and Antitumor Activity of Enantiomerically Pure [1,2‐Diamino‐1‐(4‐fluorophenyl)propane]dichloroplatinum(II) Complexes.

Dufrasne, François; Gelbcke, Michel; Schnurr, Beate; Gust, Ronald

doi:10.1002/chin.200244101

Cited by 2 publications

(6 citation statements)

References 19 publications

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“…The complexes (labeled 4-10 in Fig. 1) have been synthesized using the methods we detailed previously (16)(17)(18)(19). Briefly, the diamines have been obtained starting from diversely substituted benzaldehyde derivatives and through the hydrocyanation of their corresponding imines followed by the reduction of the nitrile (21).…”

Section: Methodsmentioning

confidence: 99%

“…Then the complexes were isolated by reaction of the diamines with K 2 PtCl 4 (precipitation, filtration, washing with 2 N HCl and drying at 60˚C under vacuum) (22). All of these compounds have been characterized by 1 H-and 13 C-NMR and IR (16)(17)(18)(19)21,22 The cells were incubated at 37˚C in sealed (airtight) Falcon plastic dishes (Nunc, Invitrogen SA, Merelbeke, Belgium) in a humidified atmosphere of 5% CO 2 . The cells were kept in exponential growth phase in MEM medium supplemented with 10% fetal bovine serum (FBS), 1% penicillin/ streptomycin (an antibiotic/antimycotic solution) and 1% kanamycin to prevent mycoplasms.…”

Section: Methodsmentioning

confidence: 99%

“…Our group has already synthesized various Pt(II) complexes structurally related to 1-phenyl-alkane-1,2-diamines (Fig. 1); those substituted by a fluorine atom at position 4 of the aromatic ring display significant anticancer activity in vitro (16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

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Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

Berger

Gasper²,

Lamoral-Theys³

et al. 2010

Int J Oncol

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Abstract. Platinum complexes remain widely used to combat various types of cancers. Three platinum complexes, cisplatin, carboplatin and oxaliplatin, are marketed for various oncological purposes. Additionally, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval for oncology purposes. Furthermore, various platinum derivatives are currently under clinical trials. More than 40 years after their discovery, however, the precise mechanism of action of platinum antitumor complexes remains elusive, partly because these compounds display numerous intracellular targets. Structure-activity-relationship analyses are therefore difficult to conduct to optimize the synthesis of novel platinum derivatives. The aim of the present study is to illustrate the potential of using Fourier Transform Infrared (FTIR) analyses to monitor the cellular modifications induced by the new platinum derivatives that we have synthesized. We show in the present study the advantages of combining an in vitro assay to determine the IC 50 growth inhibition concentrations of a series of compounds belonging to a given chemical series and FTIR analyses carried out at the IC 50 concentrations for each compound to identify potential hits within this series of compounds. The original pharmacological approach proposed here could, therefore, avoid large-scale pharmacological experiments to find hits within a given chemical series.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

Berger

Gasper²,

Lamoral-Theys³

et al. 2010

Int J Oncol

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show abstract

“…The introduction of a more stable bound cyclobutane-1,1-dicarboxylato group (see carboplatin) did not fully optimize the properties of the complexes . Thus, we tried to reduce the strong hydrophobic interactions in the crystals that are responsible for the low water solubility by exchanging one aromatic ring in meso - 4F-PtCl 2 / rac - 4F-PtCl 2 by an alkyl chain. − It was also expected that the reduced size of the alkyl chain would increase the binding kinetic to the DNA because of a reduced hindrance during a nucleophilic attack at the platinum(II). Indeed, the growth-inhibitory effects of the resulting dichloridoplatinum(II) complexes depended on the substituent at C2 in the following manner: 4-fluorophenyl ≤ methyl < ethyl ≈ propyl ≈ butyl.…”

Section: Introductionmentioning

confidence: 99%

“…To cope with these discrepancies, we decided to hydroxylate the C2 alkyl group of the diastereomeric [1,2-diamino-1-(4-fluorophenyl)propane/butane]dichloridoplatinum(II) complexes, and we studied the influence of this structural modification on lipophilicity, aqueous solubility, cytotoxicity, and antiproliferative efficacy on an enhanced panel of tumor cell lines. Because the separation into enantiomers brought only a negligible advantage, − all experiments were performed with the racemic mixtures of the novel complexes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Pharmacological Behavior of Platinum(II) Complexes Containing 1,2-Diamino-1-(4-fluorophenyl)-2-alkanol Ligands

et al. 2013

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In continuation of our effort to optimize the pharmacological profile of [1,2-diamino-1,2-bis(4-fluorophenyl)ethane]dichloridoplatinum(II) complexes, we synthesized [1,2-diamino-1-(4-fluorophenyl)alkanol]dichloridoplatinum(II) analogs. The aim of this study was to evaluate the influence of hydroxyl groups at the C2 moiety on aqueous solubility, lipophilicity, cellular platinum accumulation, and cytotoxicity against MDA-MB-231, U-937, RAJI, and SC-1 cells as well as against cisplatin-sensitive and cisplatin-resistant A2780 and A2780cisR ovarian carcinoma cells. As expected, the OH groups improved the water solubility and decreased the lipophilicity of the neutral ligands, resulting in complexes with favorable pharmacokinetic properties. The cellular uptake of the compounds in MDA-MB-231 and U-937 cells proved to depend on the configuration and showed only a slight correlation with lipophilicity. The most active complexes were R,R/S,S configured, which points to a carrier-mediated mode of action. [threo-1,2-Diamino-1-(4-fluorophenyl)propan]dichloridoplatinum(II) and [threo-2,3-diamino-3-(4-fluorophenyl)propan-1-ol]dichloridoplatinum(II) possessed only low cross-resistance to cisplatin and were up to 10-fold more active in lymphoma cell lines.

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Synthesis and Antitumor Activity of Enantiomerically Pure [1,2‐Diamino‐1‐(4‐fluorophenyl)propane]dichloroplatinum(II) Complexes.

Cited by 2 publications

References 19 publications

Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

Synthesis and In Vitro Pharmacological Behavior of Platinum(II) Complexes Containing 1,2-Diamino-1-(4-fluorophenyl)-2-alkanol Ligands

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