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71.
Daniel J. Norman Alessia Gambardella Andrew R. Mount Alan F. Murray Mark Bradley 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(40):14327-14330
A ruthenium‐based mitochondrial‐targeting photosensitiser that undergoes efficient cell uptake, enables the rapid catalytic conversion of PtIV prodrugs into their active PtII counterparts, and drives the generation of singlet oxygen was designed. This dual mode of action drives two orthogonal cancer‐cell killing mechanisms with temporal and spatial control. The designed photosensitiser was shown to elicit cell death of a panel of cancer cell lines including those showing oxaliplatin‐resistance. 相似文献
72.
Dr. Glwadys Gagnot Dr. Vincent Hervin Dr. Eloi P. Coutant Dr. Sophie Goyard Dr. Yves Jacob Dr. Thierry Rose Fatima Ezzahra Hibti Dr. Alessia Quatela Dr. Yves L. Janin 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(6):2112-2123
In this work on the design and studies of luciferins related to the blue-hued coelenterazine, the synthesis of heterocyclic analogues susceptible to produce a photon, possibly at a different wavelength, is undertaken. Here, the synthesis of O-acetylated derivatives of imidazo[1,2-b]pyridazin-3(5 H)-one, imidazo[2,1-f][1,2,4]triazin-7(1 H)-one, imidazo[1,2-a]pyridin-3-ol, imidazo[1,2-a]quinoxalin-1(5 H)-one, benzo[f]imidazo[1,2-a]quinoxalin-3(11 H)-one, imidazo[1′,2′:1,6]pyrazino[2,3-c]quinolin-3(11 H)-one, and 5,11-dihydro-3 H-chromeno[4,3-e]imidazo[1,2-a]pyrazin-3-one is described thanks to extensive use of the Buchwald–Hartwig N-arylation reaction. The acidic hydrolysis of these derivatives then gave solutions of the corresponding luciferin analogues, which were studied. Not too unexpectedly, even if these were “dressed” with substituents found in actual substrates of the nanoKAZ/NanoLuc luciferase, no bioluminescence was observed with these compounds. However, in a phosphate buffer, all produced a light signal, by chemiluminescence, with extensive variations in their respective intensity and this could be increased by adding a quaternary ammonium salt in the buffer. This aspect was actually instrumental to determine the emission spectra of many of these luciferin analogues. 相似文献
73.
Dr. Alessia Colombo Dr. Mattia Fontani Prof. Claudia Dragonetti Prof. Dominique Roberto Prof. J. A. Gareth Williams Dr. Rossella Scotto di Perrotolo Dr. Francesca Casagrande Dr. Sara Barozzi Dr. Simona Polo 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(33):7948-7952
Curcumin has chemopreventative properties against a variety of tumours, but has poor bioavailability. Here, two new bis-cyclometallated iridium(III) complexes have been prepared, featuring the natural product curcumin (CUR) or its reduced form, tetrahydrocurcumin (THC), as bidentate, anionic O O-binding ligands. The iridium THC complex is highly luminescent in deoxygenated solution and efficiently generates singlet oxygen under aerated conditions, whereas in the CUR analogue, other non-radiative decay pathways are competitive. The complexes are rapidly taken up by a variety of human tumour cell lines from solutions of micromolar concentration. They show negligible cytotoxicity in the absence of irradiation. When briefly irradiated with visible light, Ir-THC becomes highly phototoxic, inducing rapid apoptosis within 2 h. The results show the high potential of such complexes as sensitizers in photodynamic therapy (PDT). 相似文献
74.
Barbara Cardinali Gianluigi Lunardi Enrico Millo Andrea Armirotti Gianluca Damonte Aldo Profumo Stefania Gori Giuseppina Iacono Alessia Levaggi Lucia Del Mastro 《Analytical and bioanalytical chemistry》2014,406(18):4557-4561
Trastuzumab, a humanized monoclonal antibody directed against the epidermal growth factor receptor 2 (HER2), is a milestone in the treatment of HER2-overexpressing breast cancer patients. An enzyme-linked immunosorbent assay (ELISA) for trastuzumab has been developed for routine use in the laboratory to support clinical and pharmacokinetic studies to optimize therapy. The method relies on an antigen peptide linked to a 96-well plate via the streptavidin/biotin system. The peptide sequence mimics the extracellular portion of the HER2 receptor that is recognized by trastuzumab. The calibration range of the assay is 10 to 360 ng/mL per well, corresponding to a trastuzumab serum concentration from 5 to 180 μg/mL with a lower limit of quantification of 10 μg/mL. Validation results demonstrate that trastuzumab can be accurately and precisely quantified in human serum using this assay. The procedure was also tested in sera obtained from breast cancer patients to evaluate trastuzumab serum levels, confirming the applicability of method that could be a valid assay to use in daily laboratory practice. 相似文献
75.
76.
Giovanna Cancelliere Alessia Ciogli Ilaria D’Acquarica Francesco Gasparrini Jelena Kocergin Domenico Misiti Marco Pierini Harald Ritchie Patrizia Simone Claudio Villani 《Journal of chromatography. A》2010,1217(7):990-999
Three brush-type chiral stationary phases (CSPs) differing in the particle size of the starting silica particles have been prepared by covalent grafting of the π-acidic bis-(3,5-dinitrobenzoyl)-derivative of trans-1,2-diaminocyclohexane (DACH-DNB). Starting silica particles of 4.3, 2.6 and 1.9 micron were used to generate the final CSPs using an improved, highly reproducible synthetic methodology, that allowed to assemble and surface-graft the whole chiral selector in only two steps. The different CSPs have been packed in columns of various length and diameters, and fully characterized in terms of flow permeability, kinetic performances and enantioselectivity using a set of test solutes. Very high speed and high resolution applications together with stereodynamic HPLC examples are demonstrated on the columns with reduced particle diameters, on which separations of several enantiomeric pairs are routinely obtained with analysis times in the 15–40 s range. 相似文献
77.
Elena Badaloni Walter Cabri Alessia Ciogli Ilaria D’Acquarica Roberto Deias Francesco Gasparrini Fabrizio Giorgi Dorina Kotoni Claudio Villani 《Journal of chromatography. A》2010,1217(7):1024-1032
The aim of the present study was to extend the use of the “Inverted Chirality Columns Approach (ICCA)” previously developed for the identification and quantitation of the trace enantiomer in highly enriched samples of the camptothecin (CPT) family of drugs to a novel water-soluble CPT derivative, namely namitecan (ST1968), currently undergoing phase I clinical trials as anticancer agent. Namitecan, identified from a series of hydrophilic 7-oxyiminomethyl derivatives, contains a free terminal amino group, which traditionally hampers the analysis under normal-phase HPLC conditions. Nevertheless, commercially available Pirkle-type chiral stationary phases (CSPs) available in both the enantiomeric forms (i.e., having the same bound selector with opposite configuration) mainly operate under normal-phase HPLC conditions. For this reason, namitecan was pre-column N-protected with isocyanates A–D and their sulfur analogues E–H to reduce its polarity by converting the amino group into a fragment compatible with the chiral recognition mechanism (i.e., ureido and thioureido groups). Once the optimal columns system and derivatizing agents were selected, an original enantioselective HPLC–MS/MS technique was developed on the Whelk-O1 CSPs. 相似文献
78.
We correct the statements of Theorems 9 and 10 of [A. Cattabriga, M. Mulazzani, Extending homeomorphisms from punctured surfaces to handlebodies, Topology Appl. 155 (2008) 610–621], by adding missing generators, and improve the statement of Theorem 10, by removing some redundant generators. 相似文献
79.
Viola G Salvador A Vedaldi D Fortunato E Disarò S Basso G Queiroz MJ 《Journal of photochemistry and photobiology. B, Biology》2006,82(2):105-116
The antiproliferative activity, upon UVA irradiation, of two tetracyclic derivatives of benzo[b]thiophenes and pyridines, a benzo[b]thienopyridopyrimidone (1) and a thienocarboline (2), has been investigated in a panel of human tumor cell lines. The two compounds present a remarkable cytotoxicity after UVA irradiation (365 nm), reaching an IC50 of 0.1 microM in the leukaemia cell lines and 0.3-0.5 microM in the solid tumour cell lines. Their effect on the cell cycle was measured by flow cytometry in Jurkat cells. The compounds induce cell cycle perturbations and trigger a massive apoptosis as revealed by the externalisation of Annexin V-targeted residues at the outer plasmatic membrane. Furthermore the drugs induce, upon UVA irradiation significant variations of the mitochondrial potential (Deltapsi(mt)) measured by flow cytometry using the fluorochrome JC-1. In addition we characterized the mitochondrial production of reactive oxygen species (ROS) using the probe dihydroethidine (HE) and the oxidations of the mitochondrial phospholipid cardiolipin using the interacting probe nonyl acridine orange (NAO). Both compounds stimulate the production of ROS, and remarkably induce oxidation of cardiolipin. We have investigated the DNA-binding properties of these two compounds by means of UV-Vis spectroscopy and fluorescence. The two compounds exhibit a low affinity toward the macromolecule. The mode of binding was also investigated by means of flow linear dichroism (LD) which has revealed that the two compounds do not efficiently intercalate into DNA. Finally, the DNA-photocleavaging properties of the test compounds were studied on pBR322 plasmid DNA as a model. Only compound 1 is able to induce a significant production of single strand breaks only after digestion with the base excision repair enzyme Endo III. Altogether these data suggest that DNA is not a preferential target of these molecules and other subcellular structures may be responsible for their high phototoxic activity. 相似文献
80.
Marcos M Cano P Fantazzini P Garavaglia C Gomez S Garrido L 《Magnetic resonance imaging》2006,24(1):89-95
Porous substrates made of poly(3-hydroxybutyrate-3-hydroxyvalerate) (PHBHV) were prepared by a particulate leaching method. After removing the salt by extraction in water, proton nuclear magnetic resonance (NMR) relaxometry and imaging were performed on sets of PHBHV substrates immersed in phosphate-buffered solution during 3 months at different time points. Polarized optical microscopy studies were performed on thin sections, 25 and 5 mum, of the PHBHV samples. The results of NMR relaxometry showed two (1)H nuclei populations, well distinguishable on the free induction decay (FID), due to the different decay time constants, a factor of 10(2) apart. Thus, it was possible to separate the two populations, giving separate distributions of T(1) relaxation times. One population could be associated with water protons in the pores and the other to macromolecular protons. The distributions of T(1) and T(2) of the water proton shifted to lower values with increasing immersion time to a constant value after 30 days. The results obtained by NMR imaging showed an initial increase in the apparent porosity, reaching a plateau after 25 days of immersion. This increase is attributed mainly to the absorption of water in the microporosity as supported by the results of the relaxometry measurements and shown by scanning electron microscopy. The average porosity measured by NMR imaging at the plateau, 78+/-3%, is slightly higher than that determined by optical microscopy, 73+/-9%, which may be due to the fact that the latter method did not resolve the microporosity. Overall, the results suggest that at early stages after immersing the scaffolds in the aqueous medium, first 30 days approximately, NMR imaging could underestimate the porosity of the substrate. 相似文献