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1.
Dorota Bartusik Boguslaw Tomanek Erika Lattová Jack Tuszynski Gino Fallone 《Bioorganic chemistry》2010,38(1):1-6
It was shown, that cultured ex vivo human T-Lymphoblastoid (CEM) cells respond to synthesized thiocolchicine and fluorine thiocolchicine derivatives. The preparation of derivatives with substitution at C-3 and C-7 is described. All compounds were used at concentration from 1 nM to 1000 nM. Inhibitory effects of these compounds were examined in the three-dimensional (3-D) culture and cells morphology during treatment was monitored using 9.4 T MRI system. We performed studies of these compounds in CEM cells ex vivo using 1H and 19F Magnetic Resonance Imaging (MRI), 19F Magnetic Resonance Spectroscopy (MRS), High Performance Liquid Chromatography coupled with Ultra Violet (HPLC-UV) and Electron Impact Mass Spectrometry (EIMS). The results of the multi-technique approach are consistent with the fact that the new derivatives are more efficient than colchicine and thiocolchicine ex vivo. 相似文献
2.
Gianfranco Bellachioma Barbara Binotti Giuseppe Cardaci Carla Carfagna Alceo Macchioni Stefano Sabatini Cristiano Zuccaccia 《Inorganica chimica acta》2002,330(1):44-51
Complexes [M(η1,η2-C8H12OMe)((2,6-(R)2---C6H3)N=C(R′)---C(R′)=N((2,6-(R)2---C6H3))]PF6 (where M=Pd, R=H and R′2=Me2 (1), M=Pd, R=Me and R′2=Me2 (2), M=Pd, R=Et and R′2=Me2 (3), M=Pd, R=iPr and R′2=Me2 (4), M=Pd, R=iPr and R′2=An (5), M=Pt, R=iPr and R′2=An (6)) were synthesized by the reaction of [M(η1,η2-C8H12OMe)Cl]2 with the appropriate α-diimine ligand in the presence of NH4PF6. Their ion pair structure in solution was investigated by detecting dipolar interactions between protons belonging to the cation and fluorine nuclei of the anion (interionic contacts) in the 19F, 1H-HOESY NMR spectra. In complexes 1–4, the anion in solution is located close to the peripheral protons of the α-diimine ligand and it interacts with the R′ protons and with the R protons that point toward the R′ groups. The steric protection of apical position exerted by the R substituents is clearly illustrated by the absence of interionic contacts between any protons of the cycloctenylmethoxy-moiety and the anion for R≥Me in 1–4. In complexes 5 and 6 the interactions between the anion and the peripheral N,N protons also predominate but other anion–cation orientations are significantly present and, consequently, the interionic structure is less specific. 相似文献
3.
C, N CP MAS and high resolution multinuclear NMR study of methyl
Four new derivatives of methyl
were studied by 1H, 13C, 15N NMR in CDCl3 solutions and by 13C, 15N NMR in the solid state. The replacement of one aryl substituent by another has no influence on the proton and carbon chemical shifts within the sugar moiety, in solution. The differences in 13C chemical shifts Δ = δliquid - δsolid are significant for C-3 (deshielding of -3.4 to -3.8 ppm), C-5 and OMe but not observed for C-2, where the ureido substituent is linked, thus indicating that this fragment of the structure is rigid. The values of Δ in 15N chemical shifts of N-3′ are -2.3 to -2.8 ppm (increase of shielding in the solids); the effect of replacement of substituent at aromatic ring is larger than the contribution of intermolecular H-bond interaction. The values of 15.5–16.1 Hz for 1JC-1′-N and 21.2–21.5 Hz for 1JCO-N indicate that the two C---N-3′ bonds are of significant double bond character. 相似文献
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4.
Dorota Bartusik Boguslaw Tomanek Danuta Siluk Gino Fallone 《Analytical biochemistry》2009,387(2):315-3236
The aim of this study was to determine the role of δ-tocopherol in breast cancer cell growth ex vivo. Human gland mammary adenocarcinoma (MCF-7) and human T-lymphoblastoid (CEM) cells were cultured in the presence of δ-tocopherol at various concentrations (0-750 μM) for 5 days. We have grown 3D ex vivo breast cancer cell cultures in the hollow fiber bioreactor (HFBR). 19F magnetic resonance imaging (MRI) was used to evaluate oxygen concentration in the cell suspension and thus its viability. 相似文献
5.
Krasikova RN Kuznetsova OF Fedorova OS Maleev VI Saveleva TF Belokon YN 《Bioorganic & medicinal chemistry》2008,16(9):4994-5003
O-(2′-[18F]fluoroethyl)-l-tyrosine ([18F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of 18F (110 min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [18F]FET, based on NiII complex of a Schiff’s base of (S)-[N-2-(N′-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X = OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a–c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a–c (4.5–5.0 mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 °C for 5 min, followed by (2) removal of protective groups by treating with 0.5 M HCl (120 °C, 5 min). The major advantages of this procedure are retention of enantiomeric purity during the 18F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a–c. Radiochemically pure [18F]FET was isolated by semi-preparative HPLC (C18 μ-Bondapak, Waters) eluent aq 0.01 M CH3COONH4, pH 4/C2H5OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55 min. In a series of compounds 3a–c, tosyl derivative 3a provided highest radiochemical yield (40–45%, corrected for radioactive decay). Enantiomeric purity was 94–95% and 96–97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat’s tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues. 相似文献
6.
Feng Xu Jian-Xing Jiang Run-Cang Sun Dai She Bai Peng Jin-Xia Sun John F. Kennedy 《Carbohydrate polymers》2008,73(4):612-620
Esterification of wheat straw hemicelluloses with acetyl chloride, propionyl chloride, n-octanoyl chloride, lauroyl chloride, palmitoyl chloride, stearoyl chloride, and oleoyl chloride, respectively, using N-bromosuccinimide (NBS) as a catalyst was achieved in DMF/LICl medium by microwave irradiation. The effects of various acyl chlorides and the molar ratios of xylose units in hemicelluloses/acyl chloride on the degree of substitution (DS) were investigated and DS reached up to 1.34 by a few minutes. 13C NMR studies showed that the esterification occurred preferentially at the C-3 and C-2 positions. On the other hand, microwave irradiation brought a partial degradation of the polymer, and therefore resulted in a slight decrease in thermal stability of the hemicellulosic derivatives in comparison with conventional heating technique. 相似文献
7.
Fujinaga M Yamasaki T Kawamura K Kumata K Hatori A Yui J Yanamoto K Yoshida Y Ogawa M Nengaki N Maeda J Fukumura T Zhang MR 《Bioorganic & medicinal chemistry》2011,19(1):102-110
The purpose of this study was to synthesize 6-[1-(2-[18F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline ([18F]FPTQ, [18F]7a) and to evaluate its potential as a positron emission tomography ligand for imaging metabotropic glutamate receptor type 1 (mGluR1) in the rat brain. Compound [18F]7a was synthesized by [18F]fluorination of 6-[1-(2-bromo-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline (7b) with potassium [18F]fluoride. At the end of synthesis, 1280-1830 MBq (n = 8) of [18F]7a was obtained with >98% radiochemical purity and 118-237 GBq/??mol specific activity using 3300-4000 MBq of [18F]F−. In vitro autoradiography showed that [18F]7a had high specific binding with mGluR1 in the rat brain. Biodistribution study using a dissection method and small-animal PET showed that [18F]7a had high uptake in the rat brain. The uptake of radioactivity in the cerebellum was reduced by unlabeled 7a and mGluR1-selective ligand JNJ-16259685 (2), indicating that [18F]7a had in vivo specific binding with mGluR1. Because of a low amount of radiolabeled metabolite present in the brain, [18F]7a may have a limiting potential for the in vivo imaging of mGluR1 by PET. 相似文献
8.
Sun Y Takaoka Y Tsukiji S Narazaki M Matsuda T Hamachi I 《Bioorganic & medicinal chemistry letters》2011,21(15):4393-4396
In this study, assisted by affinity-guided DMAP strategy, we developed a novel 19F-modified lectin as a biosensor for specific detection and imaging of glycoproteins. Exploited the large chemical shift anisotropy property of 19F nuclei, glycoproteins detected by our 19F-biosensor are signatured by broadened peaks in 19F NMR, hence enabled the distinction between glycoproteins and small molecule saccharides. Such signal on/off switching was also applied to glycoprotein imaging by 19F MRI. 相似文献
9.
Nitrate-selective microelectrodes were used to measure not only nitrate activity in the cytoplasm and vacuole of barley (Hordeum vulgare L.) root cells, but also the tonoplast electrical membrane potential. For epidermal cells, the mean cytoplasmic and vacuolar pNO3 (-log10 [NO3]) values were 2.3±0.04 (n=19) and 1.41±0.03 (n=35), respectively, while for cortical cells, the mean cytoplasmic and vacuolar nitrate values were 2.58±0.18 (n=4) and 1.17±0.06 (n=13), respectively. These results indicate that the accumulation of nitrate in the vacuole must be an active process. Proton-selective microelectrodes were used to measure the proton gradient across the tonoplast to assess the possibility that nitrate transport into the vacuole is mediated by an H+/NO
3
–
antiport mechanism. For epidermal cells, the mean cytoplasmic and vacuolar pH values were 7.12±0.06 (n=10) and 4.93±0.11 (n=22), respectively, while for cortical cells, the mean cytoplasmic and vacuolar pH values were 7.24±0.07 (n=3) and 5.09±0.17 (n=7), respectively. Calculations of the energetics for this mechanism indicate that the observed gradient of nitrate across the tonoplast of both epidermal and cortical cells could be achieved by an H+/NO
3
–
antiport with a 11 stoichiometry.Abbreviations and Symbols G/F
free-energy change for H+/NO
3
–
antiport
- F
Faraday constant
- pHc
cytoplasmic pH
- pHv
vacuolar pH
- p[NO3]c
log10 (cytoplasmic [NO
3
–
])
- P[NO3]v
-log10 (vacuolar [NO3])
We wish to thank Dr. K. Moore for assistance with statistical analysis. 相似文献
10.
Iddon L Leyton J Indrevoll B Glaser M Robins EG George AJ Cuthbertson A Luthra SK Aboagye EO 《Bioorganic & medicinal chemistry letters》2011,21(10):3122-3127
A novel class of alkyne linked [Tyr3]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [18F]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr3]octreotate analogues, G-TOCA (3a) and βAG-TOCA (5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [18F]2-fluoroethyl triazole linked [Tyr3]octreotate analogues FET-G-TOCA (3b) and FET-βAG-TOCA (5b) under mild conditions and with short synthesis times (5 min at 20 °C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET-βAG-TOCA have high affinity for the somatostatin receptor with IC50 of 4.0 ± 1.4, and 1.6 ± 0.2 nM, respectively. 相似文献
11.
《Bioorganic & medicinal chemistry》2020,28(11):115465
Glycyrrhetinic acid (GA), the major bioactive pentacyclic triterpene aglycone of licorice root, was known to play a vital role in anti-ulcer, anti-depressant, anti-inflammatory, and anti-allergic. In this study, we semi-synthesized five GA derivatives by a series of chemical reactions. They were selected as substrates for the biotransformation and yielded thirteen metabolites by Bacillus subtilis ATCC 6633 and Bacillus megaterium CGMCC 1.1741. Their structures were identified on the basis of extensive spectroscopic methods and nine of them were found for the first time. Two main types of reactions, regio- and stereo-selective hydroxylation and glycosylation, especially in the unactivated C-H bonds including C-11, C-19 and C-27, were observed in the biotransformation process, which greatly expand the chemical diversities of GA derivatives. All compounds were tested for their inhibitory effects on nitric oxide (NO) generation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Among them, olean-12-ene-3β,7β,15α,19α,30-pentol (16) and olean-12-ene-3β,7β,15α,27,30-pentol (17) showed significant inhibitory effect with IC50 values of 0.64 and 0.07 μM, respectively. 相似文献
12.
Nahum Rosenberg Lise Bettman Orit Rosenberg Michael Soudry Moshe Gavish Rachel Bar-Shalom 《Cytotechnology》2007,54(1):1-4
An evaluation of human osteoblast metabolism usually involves measurements of the by-products of bone matrix elaboration.
The assessment of glycolytic activity of osteoblasts is not a standard tool in most of the reports, but might be of value
by providing a direct indicator of cellular metabolism. Measurement of the incorporation of [18F]-fluorodeoxyglucose, which is not further degradable following its conversion into glycose-6-phosphate during glycolysis
and is trapped in this form within the cells, can be used as an effective research tool for estimation of osteoblast metabolism.
In order to estimate the [18F]-fluorodeoxyglucose incorporation we used cultured human osteoblast-like cells. Following incubation of the culture samples
in a glucose free medium with 5 μ Ci [18F]-fluorodeoxyglucose we measured the radioactivity of the cell fraction, as a percent from the initial dose, and compared
to the incorporation values in cells treated by protoporphyrine IX (10−5 M), an endogenous pro-apoptotic agent. To compare the response of [18F]-fluorodeoxyglucose incorporation studies, following treatment of cells with the protoporphyrine IX, to other experimental
cell metabolism evaluation methods, we performed a parallel comparison of alkaline phospatase activity, which is a standard
measurement tool of osteoblast metabolism, in the control and treatment groups. A narrow range of 0.22–1.36% of [18F]-fluorodeoxyglucose incorporation per million cells was found. Additionally in the protoporphyrine IX treated cells a significant
62% decrease of [18F]-fluorodeoxyglucose incorporation was observed (p < .05). A parallel significant decrease in alkaline phosphatase activity (p < .001) was found in the cells treated by the protoporphyrine IX. Therefore we suggest that the presented method of [18F]-fluorodeoxyglucose incorporation measurement can be utilized as an effective research tool for estimation of the cellular
glycolitic activity in human osteoblast-like cells in vitro. 相似文献
13.
《Carbohydrate research》1985,138(1):65-72
Treatment of peptidoglycan monomer (1) from Brevibacterium divaricatum with aqueous ammonia led to cleavage of the C-3 ether linkage in the N-acetylmuramoyl residue to give the d-lactoylpentapeptide and a saturated disaccharide. By using 13C-n.m.r. spectroscopy, the disaccharide was identified as chitobiosamine. Alkaline treatment of model compounds under similar conditions showed that N-acetylmuramoyl derivatives with C-1 unsubstituted undergo cleavage at C-3 to give the corresponding 2-acetamido-2-deoxy-d-glucopyranose derivative. The reaction of 1 with ammonia was monitored by 1H-n.m.r. spectroscopy and, from the data obtained, rate constants and the activation energy were calculated. 相似文献
14.
Prakash Radhakrishnan Vishwanath Chachadi Ming-Fong Lin Rakesh Singh Reiji Kannagi Pi-Wan Cheng 《Biochemical and biophysical research communications》2011,409(3):436
Sialyl Lewis x (sLex) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLex antibody, and anti-6-sulfo-sialyl Lewis x antibody by 12%, 240%, 43%, 248% and 21%, respectively. Also, the expression of C2GnT-1, B4GalT1, GlcNAc6ST3, and ST3Gal3 genes was significantly upregulated. Further treatment of TNFα-treated cells with either anti-sLex antibody or E-selectin significantly suppressed their in vitro migration (81% and 52%, respectively) and invasion (45% and 56%, respectively). Our data indicate that TNFα treatment enhances the motility and invasion properties of LNCaP C-81 cells by increasing the formation of selectin ligands through stimulation of the expression of selective glycosyl- and sulfotransferase genes. These results support the hypothesis that inflammation contributes to cancer metastasis. 相似文献
15.
Marco A. Marra Shiv S. Prasad David L. Baillie 《Molecular & general genetics : MGG》1993,236(2-3):289-298
Summary A previous study of genomic organization described the identification of nine potential coding regions in 150 kb of genomic DNA from the unc-22(IV) region of Caenorhabditis elegans. In this study, we focus on the genomic organization of a small interval of 0.1 map unit bordered on the right by unc-22 and on the left by the left-hand breakpoints of the deficiencies sDf9, sDf19 and sDf65. This small interval at present contains a single mutagenically defined locus, the essential gene let-56. The cosmid C11F2 has previously been used to rescue let-56. Therefore, at least some of C11F2 must reside in the interval. In this paper, we report the characterization of two coding elements that reside on C11F2. Analysis of nucleotide sequence data obtained from cDNAs and cosmid subclones revealed that one of the coding elements closely resembles aromatic amino acid decarboxylases from several species. The other of these coding elements was found to closely resemble a human growth factor activatable Na+/H+ antiporter. Pairs of oligonucleotide primers, predicted from both coding elements, have been used in PCR experiments to position these coding elements between the left breakpoint of sDf19 and the left breakpoint of sDf65, between the essential genes let-653 and let-56. 相似文献
16.
Juan Xiong Masatoshi Taniguchi Yoshiki Kashiwada Michiko Sekiya Takashi Yamagishi Yoshihisa Takaishi 《Bioorganic & medicinal chemistry》2010,18(8):2964-2975
Forty-one derivatives of papyriferic acid were prepared based on our previous finding that methyl papyriferate (3) showed potent reversing effect on cytotoxicity of colchicine against multidrug resistance (MDR) human cancer cells (KB-C2), and evaluated for their cytotoxicity and effect on reversing P-gp-mediated MDR against KB-C2 cells. 3-O-(Morpholino-β-oxopropanoyl)-12β-acetoxy-3α,25-dihydroxy-(20S,24R)-epoxydammarane (37) significantly increased the sensitivity of colchicine against KB-C2 cells by 185-fold at 5 μg/mL (7.4 μM), and the cytotoxicity of colchicine was recovered to nearly that of sensitive (KB) cells. The other several new amide derivatives also exhibited potent reversal activity comparable to or more potent than methyl papyriferate and verapamil. 相似文献
17.
The following primary sulphonates have been converted into the corresponding deoxyfluoro derivatives by reaction with potassium fluoride in ethylene glycol:1,2:3,4-di-O-isopropylidene-6-O-tosyl α-D-galactopyranose (1), methyl 2,3-O2-isopropyliden-5-O-tosyl-α,β-D-ribofuranoside (2), 1,2:3,4-di-O-methylene-6-O-tosyl-α-D-glucofuranose (3), 3,5-di-O-benzylidene-1,2-O-isopropylidene-6-O-tosyl-α-D-glucofuranose (4), and 1,2:3,5-di-O-isopropylidene-6-O-tosyl-α-D-glucofuranose (5). The yields were generally poor; in the reaction of 1, a major by-product was 6-O-(2-hydroxyethyl)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (11). The reaction of the primary hydroxyl precursor of each of the above tosylates with N2-(2-chloro- 1,1,2-trifluoroethyl)-N,N-diethylamine generally yielded the O-chlorofluoroacetyl derivative; however, 1,2:3,5-di-O-methylene-α-D-glucofuranose (12) was converted into the 6-deoxy-6-fluoro derivative (8). The 19F resonances of compounds containing the CH2F moiety fall between φC +213 and φC +235 p.p.m. The differences between the vicinal19F-1H couplings of compounds having the D-gluco and D-galacto configurations clearly reflect the influence of the C-4O-4 substitutents on the populations of the C-5C-6 rotamers. A novel type of noise-modulated, heteronuclear decoupling experiment is described. 相似文献
18.
Novel semisynthetic derivatives of betulin and betulinic acid with cytotoxic activity 总被引:1,自引:0,他引:1
Rita C. Santos Jorge A.R. Salvador Silvia Marín Marta Cascante 《Bioorganic & medicinal chemistry》2009,17(17):6241-6250
A series of new imidazole carboxylic esters (carbamates) and N-acylimidazole derivatives of betulin and betulinic acid (14–29) have been synthesized. The new compounds were screened for in vitro cytotoxicity activity against human cancer cell lines HepG2, Jurkat and HeLa. A number of compounds have shown IC50 values lower than 2 μM against the cancer cell lines tested and the vast majority has shown a better cytotoxicity profile than betulinic acid, including the betulin derivatives. N-Acylimidazole derivatives 26 and 27 (IC50 0.8 and 1.7 μM in HepG2 cells) and the C-3 carbamate derivative 16 (IC50 2.0 μM in HepG2 cells) were the most promising compounds. Based on the observed cytotoxicity, structure–activity relationships have been established. 相似文献
19.
15β-Hydroxy-18(4→3)-abeo-ent-kaur-4(19),16-diene (4) was biotransformed by the fungus Fusarium fujikuroi into 3α,11β,15β-trihydroxy-18(4→3)-abeo-ent-kaur-4(19),16-diene (5). The hydroxylation at C-3(α) in this diterpene reminds a similar reaction that occurs at C-13 in the biosynthesis of gibberellic acid in this fungus. The presence of the 15β-alcohol in the substrate directs the second hydroxylation at C-11(β), which had been observed in the incubation of ent-kaur-16-ene derivatives with this fungus when the C-19 hydroxylation was inhibited by the existence in the molecule of a 3α-OH or 3-oxo group. We also show that the angelate of the substrate is an undescribed natural product now identified as a component of the plant Distichoselinum tenuifolium. 相似文献
20.
Yan-Qiu Meng Dan Liu Ling-Li Cai Hong Chen Bo Cao Yi-Zheng Wang 《Bioorganic & medicinal chemistry》2009,17(2):848-854
Nineteen ursolic acid derivatives (15 novel compounds) modified at the C-3 and the C-28 positions were synthesized. The cytotoxic activity of the derivatives was evaluated against HeLa, BGC-823 and SKOV3 cells by MTT assay. Inducing apoptosis and affecting cell cycle distribution by the derivatives in HeLa cells were assessed by flow cytometry and DNA fragmentation. Compounds 10b and 11b were particularly active to inhibit HeLa cells growth through inducing apoptosis and arresting cell cycle progression. The typical ‘sub-G1 peak’ and DNA ladder formation were checked and cell cycle was arrested at the S phase in a dose-dependent manner. 相似文献