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181.
Meseguer B Alonso-Díaz D Griebenow N Herget T Waldmann H 《Chemistry (Weinheim an der Bergstrasse, Germany)》2000,6(21):3943-3957
Protein kinaseC (PKC) is linked to the signal-induced modulation of a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis, and tumor development. The design and synthesis of small molecules that regulate these different cellular signaling systems is at the forefront of modern drug design. Herein we report a) an efficient method for the synthesis of indolactamV (6), a PKC activator, and its N13-des(methyl) analogues (19) using a regioselective organometallic transformation, a convenient aminomalonate derivative (10) to introduce the appropriate functionality and an enantiospecific enzymic hydrolysis as key steps; b) the use of this method in the first solid-phase synthesis of a teleocidin library modifying the N-13, C-12 and C-7 alkyl chains, and, therefore, producing a library of potential activators and/or inhibitors of PKC of the general structure (32); c) the activation of PKC by selected members of the library using a MARCKS translocation in vivo assay system; d) the observation that some of these analogues are nearly as effective as the natural PKC activators phorbol dibutyrate and (-)-indolactam V (6), and e) the observation that some of these analogues have different potential to induce down-regulation of members of the PKC gene family after chronic stimulation. 相似文献
182.
1-Aryl-5-amino-4-(cyanoformimidoyl)imidazoles 2 were reacted with malononitrile under mild experimental conditions and led to 3-aryl-5,7-diamino-6-cyano-3H-imidazo[4,5-b]pyridines 5, when the reaction was carried out in the presence of DBU, or to 3-aryl-5-amino-6,7-dicyano-3H-imidazo[4,5-b]pyridines 3, in its absence. Both reactions evolved from the adduct formed by nucleophilic attack of the malononitrile anion to the carbon of the cyanoformimidoyl substituent. A 5-amino-1-aryl-4-(1-amino-2,2-dicyanovinyl)imidazole 4 was isolated when this reaction was carried out in the presence of DBU. The structure of compound 4 was confirmed by spectroscopic methods and by reaction with triethyl orthoformate and with acetic anhydride, leading respectively to 9-aryl-6-(cyanomethylidene)purines 11 and 12. Imidazole 2b was also reacted with ethyl acetoacetate, a carbon acid with a pK(a) comparable to that of malononitrile. Similar reaction conditions were used and the product isolated was a 6-carbamoyl-1,2-dihydropurine 10, showing that a different mechanism was operating in this case. 相似文献
183.
The infinite-dimensional representations of thesl(n+1, ) Lie algebras (maximal representations) constructed in our previous paper are studied on the two simplest examplesn = 1,2. The sufficient condition for irreducibility of the maximal representations is proved to be also necessary in these cases. It is further shown, that our method allows us to construct other set of infinite-dimensional highest-weight representations ofsl(3, ), so calledmixed representations which are irreducible in some cases when the maximal as well as the standard highest-weight representations (Verma modules) are reducible.Dedicated to the 25th anniversary of the Joint Institute for Nuclear Research.The authors are grateful to Prof. A. A. Kirillov, Dr. A. U. Klimyk, Dr. W. Lassner and Prof. D. P. Zhelobenko for stimulating discussions. 相似文献
184.
Oxides Fe2–x
Cr
x
O3 (corundum-type) and Fe3–y
,Cr
y
O4 (spinel-type) were studied by transmission IR spectroscopy. The wavenumbers corresponding to characteristic absorption maxima depend linearly on the composition of both types of solid solutions, i.e. onx andy. The results show that IR spectroscopy can contribute to the analysis of solid solutions of iron and chromium oxides and of the oxidation products of Fe-Cr alloys.The authors are indebted to Ing. P. Holba for the preparation of synthetic oxide samples. The cooperation of Yu. Borodkin and I. Zuika (Riga) who made the measurements in the far IR region is gratefully acknowledged. 相似文献
185.
We propose a model for the production of extra (additional) lepton pairs in deep inelastic lepton-hadron scattering, e+e– annihilation and large pT processes. Extra lepton pairs are supposed to be originated by annihilations of quarks and antiquarks created during the space-time evolution of quark initiated jets. This mechanism yields predominantly dileptons with rather low masses. Predictions following from the model are compared with the recent data on trimuon production in neutrino-nucleon interactions. It is also suggested that internal hard processes can lead to dileptons with both small and large masses. The latter mechanism has rather small cross section but it is particularly interesting from the point of view of the simple quark-parton model.Dedicated to Academician Václav Votruba on the occasion of his seventieth birthday. 相似文献
186.
The experimental results obtained with the chalcogenide glass Ge15Te81S2As2 with imposed overall pressure up to 700 MPa are presented. The material exhibits the switching effect and the memory effect. It is shown that the overall pressure changes remarkably d.c. electrical conductivity of the amorphous semiconductor. It is assumed that the changes in conductivity are caused by changes in activation energy. The changes in activation energy within the range of considered pressures are, as follows from our measurements, E/p–10·95×10–5 eV/MPa +p × 10·41 W 10–7 eV/MPa2. The assumption of the activation energy dependence on pressurep are confirmed also by measurements of dependence In vs. 1/T at various pressures. 相似文献
187.
Conclusions We conclude that the occurrence of a maximum in the magnetization versus temperature curve observed under certain circumstances on U3P4 is not connected with its intrinsic magnetic structure, but substantially depends on the form in which the material is studied (polycrystalline powder, single crystal, single crystal powders with various dimensions of grains). This phenomenon seems to be affected by quenching of the state from the region of low anisotropy at higher temperature in the small particles with a strong tendency to single domain behaviour and thus it may be a consequence of rotation magnetization process in the fields relatively small for U3P4. The assertion about transitions between magnetic ordering, sometimes proposed in the literature on the basis of observed anomalies in the temperature course of magnetization without simultaneous confirmation by neutron diffraction, should be accepted with some reservation, especially in the case of simple uranium compounds. However, another situation arises for pseudobinary alloys of ferro- and antiferromagnetic components (e.g. UP0·75S0·25) where such transitions were confirmed both by magnetic methods and by neutron diffraction studies [13].The authors would like to express their thanks to Ing. A.Meovský for careful preparation of samples. 相似文献
188.
Elena Almaraz Luengo Marcos Brian Leiva Cerna Luis Javier García Villalba Julio Hernandez-Castro Darren Hurley-Smith 《Entropy (Basel, Switzerland)》2022,24(5)
This work presents an analysis of the existing dependencies between the tests of the FIPS 140-2 battery. Two main analytical approaches are utilized, the first being a study of correlations through the Pearson’s correlation coefficient that detects linear dependencies, and the second one being a novel application of the mutual information measure that allows detecting possible non-linear relationships. In order to carry out this study, the FIPS 140-2 battery is reimplemented to allow the user to obtain p-values and statistics that are essential for more rigorous end-user analysis of random number generators (RNG). 相似文献
189.
Antioxidant Activity of Polyphenols,from Mauritia flexuosa (Aguaje), Based on Controlled Dehydration
Hichem Bensaada María Fernanda Soto-Garcia Juan Carlos Carmona-Hernandez 《Molecules (Basel, Switzerland)》2022,27(10)
Plant polyphenols offer several benefits for the prevention of diverse illnesses. Fruit’s edible and inedible parts (pulp, seeds, peels, stems, flowers) are important sources of polyphenols. Different industrial processes for fruit treatment and commercialization affect the total polyphenol content (TPC), and probably the biological activity. The purpose of the present work was to determine the TPC and antioxidant activity (by DPPH) of polyphenols extracted from the pulp and seeds of Mauritia flexuosa (aguaje), in fresh and dehydrated forms, in order to determine the possible connection with the quantity of polyphenols and their specific antioxidant activity. The highest phenolic content for M. flexuosa seeds in fresh form (non-dehydrated) was 270.75 mg GAE/100 g with a 96-h extraction. With respect to the dehydrated samples, the best yield was quantified in the 96-h dehydrated seed sample. For all pulp and seeds, dehydrated for 24, 48, and 96 h, TPC showed a slightly decreasing pattern. The DPPH results were the highest in the 96-h dehydrated samples and the differences among all dehydrated pulp and seed samples were minimal. More studies testing the presence of other antioxidant components could help in understanding the detailed antioxidant activity, and related more to the specific action, rather than only total polyphenol content. 相似文献
190.
María F. Beer Guillermo F. Reta Adrin Puerta Augusto E. Bivona Andrs Snchez Alberti Natacha Cerny Emilio L. Malchiodi Carlos E. Tonn Jos M. Padrn Valeria P. Sülsen Osvaldo J. Donadel 《Molecules (Basel, Switzerland)》2022,27(10)
Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI50 values ranging between 5.3 (±0.32) and 14 (±0.90) μM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15–19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI50 values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC50 values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively. 相似文献