Synthesis, Conformational Studies, and Investigations on the Estrogen Receptor Binding of [R/S-1-(2,6-Dichloro-4-hydroxyphenyl)-ethylenediamine]platinum(II) Complexes

Gust, Ronald; Lubczyk, Veronika; Schmidt, Kathrin; Shihada, Undine

doi:10.1002/1521-4184(200103)334:3<93::aid-ardp93>3.0.co;2-2

Cited by 3 publications

(7 citation statements)

References 16 publications

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Section: Discussionmentioning

confidence: 96%

“…Exchange of the axially arranged 2-chloro-4-hydroxyphenyl ring by H results in the [1-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]diiodoplatinum(II) complex, which shows an excellent structural analogy to E2 . However, the complex induced neither luciferase expression in MCF-7-2a cells nor uterus growth in the uterotrophic test with juvenile NMRI mice.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of a phenolic ring in contact with Asp 351 in order to get hormonal activity has already been shown for derivatives of the [(1R,2S)/(1S,2R)-1-(2-chloro-4-hydroxyphenyl)-2-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]diiodoplatinum(II) complex 8-PtI 2 , also assigned to type II estrogens. 23,24,36 Exchange of the axially arranged 2-chloro-4-hydroxyphenyl ring by H results in the [1-(2,6-dichloro-4hydroxyphenyl)ethylenediamine]diiodoplatinum(II) complex, which shows an excellent structural analogy to E2. 36 2,6-dichloro-4-hydroxyphenyl ring.…”

Section: Discussionmentioning

confidence: 99%

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(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines: Ligands for the Estrogen Receptor with a Novel Binding Mode

et al. 2002

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(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines 1-7 were synthesized by the reaction of the methoxy-substituted (1R,2S)/(1S,2R)-1,2-diarylethylenediamines 1b-7b with triethyl orthoformate and subsequent ether cleavage with BBr(3). All compounds were tested for estrogen receptor (ER) binding in a competition experiment with [(3)H]-estradiol and for gene activation in a luciferase assay using ER positive MCF-7-2a breast cancer cells stably transfected with the plasmid ERE(wtc)luc. The relative binding affinities of the 2-imidazolines were very low (RBA < 0.1%). Nevertheless, 4-7 possessed full agonistic activity in the luciferase assay. The relative transcription potency increased in the order 5 (2,2'-I) < 6 (2,6-Cl(2), 2'-F) < 4 (2,2'-Cl) < 7 (2,6-Cl(2), 2'-Cl). These data together with spectroscopic and molecular modeling studies were used to investigate the preferred binding mode adopted by the imidazoline ligands. The 1,2-diarylethane pharmacophor takes a Z-stilbene-like structure with pseudoaxially oriented phenyl rings at the planar heterocyclic ring. Because of this unusual spatial structure, the (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines have to be assigned to a second class of estrogenically active compounds (type II estrogens). In contrast to type I estrogens, e.g., estradiol (E2), diethylstilbestrol (DES), and meso-hexestrol (HES), which are connected to His 524 in the binding site, type II estrogens are very likely H-bonded to Asp 351 in a hydrophobic side pocket.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines: Ligands for the Estrogen Receptor with a Novel Binding Mode

et al. 2002

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“…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). 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 .…”

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%

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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Optimization of cisplatin for the treatment of hormone-dependent tumoral diseases

Gust

Beck²,

Jaouen³

et al. 2009

Coordination Chemistry Reviews

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Synthesis, Conformational Studies, and Investigations on the Estrogen Receptor Binding of [R/S-1-(2,6-Dichloro-4-hydroxyphenyl)-ethylenediamine]platinum(II) Complexes

Cited by 3 publications

References 16 publications

(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines: Ligands for the Estrogen Receptor with a Novel Binding Mode

(4R,5S)/(4S,5R)-4,5-Bis(4-hydroxyphenyl)-2-imidazolines: Ligands for the Estrogen Receptor with a Novel Binding Mode

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

Optimization of cisplatin for the treatment of hormone-dependent tumoral diseases

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