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排序方式: 共有393条查询结果,搜索用时 31 毫秒
1.
Top S Vessières A Leclercq G Quivy J Tang J Vaissermann J Huché M Jaouen G 《Chemistry (Weinheim an der Bergstrasse, Germany)》2003,9(21):5223-5236
A series of ferrocene derivatives based upon the structure of the antiestrogenic drug tamoxifen or of its active metabolite hydroxytamoxifen has been prepared and named by analogy ferrocifens and hydroxyferrocifens. This series includes 1-[4-(O(CH(2))(n)NMe(2))phenyl]-1-phenyl-2-ferrocenyl-but-1-ene and 1-[4-(-O(CH(2))(n)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene, with n=2, 3, 5 and 8, and 1-[4-(-O(CH(2))(2)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenylethene. Most of these molecules have been synthesised by McMurry cross-coupling of the appropriate ketones, except for the ethene complexes, which were prepared by a four-step reaction sequence starting from the ferrocenylacetic acid. All these compounds were obtained as mixtures of Z and E isomers. The isomers were separated in the cases of the ferrocenyl derivatives of tamoxifen and hydroxytamoxifen (n=2). No isomerisation of the Z and E isomers occurred in DMSO after one day, while a 50:50 mixture of the isomers was obtained within one hour in chloroform. The X-ray structure of (E)-1-[4-(-O(CH(2))(2)NMe(2))phenyl]-1-(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene has been determined. The relative binding affinity (RBA) values of the hydroxyferrocifens for the estrogen receptor alpha (ERalpha) was good to moderate, with values decreasing progressively with the length of the basic chain. The RBA values found for the estrogen receptor beta (ERbeta) are equal to or slightly less than those found for the alpha form. The lipophilicity of the hydroxyferrocifens are superior to the values found for estradiol and increase with lengthening of the chain. The antiproliferative effects of the four hydroxyferrocifens with n=2, 3, 5 and 8 were studied on four breast cancer cell lines (MCF7, MDA-MB231, RTx6 and TD5) possessing different levels of ERalpha. On MCF7 cells containing high levels of ERalpha, hydroxyferrocifens behave as antiestrogens. At a molarity of 1 microM the effect is close to that of hydroxytamoxifen (used for reference) when n=2 or 5, more marked when n=3, and weaker when n=8. Ferrocene alone has no effect. For the MDA-MB231 cells, classed as a hormone-independent breast cancer cell line, on the other hand, the hydroxyferrocifens show remarkable antiproliferative behaviour while the hydroxytamoxifen is completely inactive. Hydroxyferrocifens therefore show the unique property of being active both on hormone-dependent and on hormone-independent breast cancer cell lines. The molecular modelling study provides some clues for understanding of the antagonist effect of these molecules, while an additional cytotoxic effect due to the vectorised ferrocenyl unit is revealed in some occasions. 相似文献
2.
Sun Y Irie M Kishikawa N Wada M Kuroda N Nakashima K 《Biomedical chromatography : BMC》2004,18(8):501-507
A highly sensitive HPLC method was developed for the determination of xenoestrogenic compound, bisphenol A (BPA) in human breast milk samples. After a two-step liquid-liquid extraction, BPA was derivatized with fluorescent labeling reagent, 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl). The excess fluorescent reagent could be removed effectively using a column-switching system. The separation of DIB-BPA from endogenous materials in milk was carried out on two C(18) columns and fluorescence intensity was monitored at 475 nm with the excitation of 350 nm. A good linearity (r = 0.994) was observed of BPA in the concentration range of 0.2-5.0 ng mL(-1) in breast milk, and the detection limit was 0.11 ng mL(-1) at a signal-to-noise ratio of 3. Intra- and inter-day precision (RSD, %) were less than 8.7 and 10.4, respectively. Twenty-three breast milk samples of healthy lactating women were analyzed for the BPA concentration; the mean value was 0.61 +/- 0.20 ng mL(-1), with no correlation to the lipid content of milk samples. 相似文献
3.
4.
Proteins with molecular mass (M(r)) <20 kDa are often poorly separated in 2-D sodium dodecyl sulfate polyacrylamide gel electrophoresis. In addition, low-M(r) proteins may not be readily identified using peptide mass fingerprinting (PMF) owing to the small number of peptides generated in tryptic digestion. In this work, we used a 2-D liquid separation method based on chromatofocusing and non-porous silica reversed-phase high-performance liquid chromatography to purify proteins for matrix-assisted laser desorption/ionization time-of-flight mass spectrometric (MALDI-TOFMS) analysis and protein identification. Several proteins were identified using the PMF method where the result was supported using an accurate M(r) value obtained from electrospray ionization TOFMS. However, many proteins were not identified owing to an insufficient number of peptides observed in the MALDI-TOF experiments. The small number of peptides detected in MALDI-TOFMS can result from internal fragmentation, the few arginines in its sequence and incomplete tryptic digestion. MALDI-QTOFMS/MS can be used to identify many of these proteins. The accurate experimental M(r) and pI confirm identification and aid in identifying post-translational modifications such as truncations and acetylations. In some cases, high-quality MS/MS data obtained from the MALDI-QTOF spectrometer overcome preferential cleavages and result in protein identification. 相似文献
5.
Nazia Nayeem Prof. Maria Contel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(35):8891-8917
This review focuses on studies of coordination and organometallic compounds as potential chemotherapeutics against triple negative breast cancer (TNBC) which has one of the poorest prognoses and worst survival rates from all breast cancer types. At present, chemotherapy is still the standard of care for TNBC since only one type of targeted therapy has been recently developed. References for metal-based compounds studied in TNBC cell lines will be listed, and those of metal-specific reviews, but a detailed overview will also be provided on compounds studied in vivo (mostly in mice models) and those compounds for which some preliminary mechanistic data was obtained (in TNBC cell lines and tumors) and/or for which bioactive ligands have been used. The main goal of this review is to highlight the most promising metal-based compounds with potential as chemotherapeutic agents in TNBC. 相似文献
6.
William E. Butler Paula N. Kelly Andy G. Harry Rachel Tiedt Blanaid White Rosaleen Devery Peter T. M. Kenny 《应用有机金属化学》2013,27(6):361-365
A series of N‐(ferrocenylmethyl amino acid) fluorinated benzene‐carboxamide derivatives 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i and 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N‐(fluorobenzoyl) amino acid derivatives using the standard N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride, 1‐hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L‐alanine. All of the compounds were fully characterized using a combination of 1H NMR, 13C NMR, 19F NMR, distortionless enhancement by polarization transfer (DEPT)‐135, 1H–1H correlation spectroscopy (COSY) and 1H–13C COSY (heteronuclear multiple‐quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen‐positive MCF‐7 breast cancer cell line. Compounds 4g , 4i , 5h and 5i exhibited cytotoxic effects on the MCF‐7 breast cancer cell line. N‐(Ferrocenylmethyl‐L‐alanine)‐3,4,5‐trifluorobenzene‐carboxamide ( 5h ) was the most active compound, with an IC50 value of 2.84 μm . Compounds 4i , 5h and 5i had lower IC50 values than that found for the clinically employed anticancer drug cisplatin (IC50 = 16.3 μm against MCF‐7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species‐mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
7.
Tom Miclot Dr. Camille Corbier Prof. Alessio Terenzi Cécilia Hognon Prof. Stéphanie Grandemange Prof. Giampaolo Barone Prof. Antonio Monari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(34):8865-8874
Human telomeric DNA, in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine (8oxoG) lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress. 相似文献
8.
In this study, Fe3O4@TiO2 nanoparticles were synthesized as a new Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) hybrid imaging agent and radiolabeled with 89Zr. In addition, Fe3O4 nanoparticles were synthesized and radiolabeled with 89Zr. Df-Bz-NCS was used as bifunctional ligand. The nanoconjugates were characterized with transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. Radiolabeling yields were 100%. Breast and prostate cancer cell affinities and cytotoxicity were determined using in vitro cell culture assays. The results demonstrated that Fe3O4@TiO2 nanoparticles are promising for PET/MR imaging. Finally, unlike Fe3O4 nanoparticles, Fe3O4@TiO2 nanoparticles showed a fluorescence spectrum at an excitation wavelength of 250 nm and an emission wavelength of 314 nm. Therefore, in addition to bearing the magnetic properties of Fe3O4 nanoparticles, Fe3O4@TiO2 nanoparticles display fluorescence emission. This provides them with photodynamic therapy potential. Therefore multimodal treatment was performed with the combination of PDT and RT by using human prostate cancer cell line (PC3). The development of 89Zr-Df-Bz-NCS-Fe3O4@TiO2 nanoparticles as a new multifunctional PET/MRI agent with photodynamic therapy and hyperthermia therapeutic ability would be very useful. 相似文献
9.
Bo-Hwa Choi Goutam Chakraborty Kwanghee Baek Ho Sup Yoon 《Experimental & molecular medicine》2013,45(10):e47
Here, we report that B-cell lymphoma 2 (Bcl-2) is a novel target molecule of aspirin in breast cancer cells. Aspirin influenced the formation of a complex by Bcl-2 and FKBP38 and induced the nuclear translocation of Bcl-2 and its phosphorylation. These events inhibited cancer cell proliferation and subsequently enhanced MCF-7 breast cancer cell apoptosis. Bcl-2 knockdown using small interfering RNA (siRNA) delayed apoptotic cell death, which correlated with increased proliferation following aspirin exposure. In contrast, Bcl-2 overexpression enhanced the onset of aspirin-induced apoptosis, which was also associated with a significant increase in Bcl-2 phosphorylation in the nucleus. Therefore, this study may provide novel insight into the molecular mechanism of aspirin, particularly its anticancer effects in Bcl-2- and estrogen receptor-positive breast cancer cells. 相似文献
10.
Tahereh Sadeghcheh Mohammad Saber Tehrani Hakim Faraji Parviz Aberoomand Azar Masoumeh Helalizadeh 《Journal of separation science》2022,45(7):1362-1373
A sensitive method based on liquid chromatography combined with a diode array detector was developed and validated to simultaneously determine tamoxifen, and its active metabolites N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen in human plasma samples. The green and sustainable vortex-assisted dispersive liquid-phase microextraction technique based on the natural hydrophobic deep eutectic solvent was used for the extraction and preconcentration of the analytes. Chemometrics and multivariate analysis were used to optimize the independent variables including the type and volume of deep eutectic solvent, extraction time, and ionic strength. Under optimal conditions, calibration curves were linear in a suitable range with the lower limits of quantification (0.8–10.0 μg/L), which covered the relevant concentrations of the analytes in plasma samples for a clinical study. Intra- and interday precision evaluated at three concentrations for the analytes were lower than 8.2 and 12.1%, respectively. Accuracy was in the range of 94.9–104.7%. The applicability of the developed method on human plasma samples illustrated the range 45.1–72.8, 98.4–128.3, 0.9–1.2, and 2.7–6.1 μg/L for tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen, respectively. The validated method can be effective for the pharmacokinetics, pharmacodynamics, and therapeutic drug monitoring studies of tamoxifen and its main metabolites in biological fluids. 相似文献