Herein we report novel pyrrole‐ and benzene‐based hydroxamates ( 8 , 10 ) and 2′‐aminoanilides ( 9 , 11 ) bearing the tert‐butylcarbamate group at the CAP moiety as histone deacetylase (HDAC) inhibitors. Compounds 8 b and 10 c selectively inhibited HDAC6 at the nanomolar level, whereas the other hydroxamates effected an increase in acetyl‐α‐tubulin levels in human acute myeloid leukemia U937 cells. In the same cell line, compounds 8 b and 10 c elicited 18.4 and 21.4 % apoptosis, respectively (SAHA: 16.9 %), and the pyrrole anilide 9 c displayed the highest cytodifferentiating effect (90.9 %). In tests against a wide range of various cancer cell lines to determine its antiproliferative effects, compound 10 c exhibited growth inhibition from sub‐micromolar (neuroblastoma LAN‐5 and SH‐SY5Y cells, chronic myeloid leukemia K562 cells) to low‐micromolar (lung H1299 and A549, colon HCT116 and HT29 cancer cells) concentrations. In HT29 cells, 10 c increased histone H3 acetylation, and decreased the colony‐forming potential of the cancer cells by up to 60 %. 相似文献
The efficiency of epoxy/CNT nanocomposites as photocatalyst on adsorbed, aqueous and gas phases is investigated. Epoxy films containing SWNTs in the range between 0.1 and 0.3 wt% are prepared by means of UV‐induced polymerization and the achieved materials are used as photocatalysts on adsorbed, aqueous, and gas phases. The activity of this new photocatalytic materials is evaluated in the adsorbed state by using the methylene blue target molecule, in the aqueous phase by following the photodegradation of phenol and 3,5‐dichlorophenol, and in the gas phase using nitrogen monoxide as probe molecule. It is demonstrated that the catalyst is suitable for both oxidative and reductive degradation reactions.
A catalytic asymmetric addition of nitroalkanes to alkylideneindolenines, generated in situ from arylsulfonylindoles, is presented. Despite the weakness of the non‐covalent H‐bond interactions between catalyst and substrates, the performance of the bifunctional organocatalyst used was found to be essentially unaffected by the polarity of the reaction medium. Nitroalkanes, mostly used in nearly stoichiometric amounts, could thus function both as solvents and reagents, resulting in a truly solvent‐free reaction. The broad substrate scope shown by the present transformation allowed the preparation of some optically active tryptamine precursors that are not accessible through the previous catalytic asymmetric methods. 相似文献
One of the most prominent alterations in cancer cells is their strict dependence on the glycolytic pathway for ATP generation. This observation led to the evaluation of glycolysis inhibitors as potential anticancer agents. The inhibition of lactate dehydrogenase (LDH) is a promising way to inhibit tumor cell glucose metabolism without affecting the energetic balance of normal tissues. However, the success of this approach depends chiefly on the availability of inhibitors that display good selectivity. We identified a compound (galloflavin, CAS 568‐80‐9) which, in contrast to other inhibitors of human LDH, hinders both the A and B isoforms of the enzyme. To determine the mechanism of action, we collected LDH‐A and ‐B inhibition data in competition reactions with pyruvate or NADH and evaluated the results using software for enzyme kinetics analysis. We found that galloflavin inhibits both human LDH isoforms by preferentially binding the free enzyme, without competing with the substrate or cofactor. The calculated Ki values for pyruvate were 5.46 μM (LDH‐A) and 15.06 μM (LDH‐B). In cultured tumor cells, galloflavin blocked aerobic glycolysis at micromolar concentrations, did not interfere with cell respiration, and induced cell death by triggering apoptosis. To our knowledge, the inhibition of LDH is, to date, the only biochemical effect described for galloflavin. Because galloflavin is not commercially available, we also describe herein a procedure for its synthesis and report its first full chemical characterization. 相似文献
Four milk-based ice cream samples were produced by heating (65°C) the ingredients at different pressures (0.5, 1.0 bar) and times (5, 30 min). Overrun, melting behaviour, particle size, viscosity and sensory analysis were conducted for each time/temperature combination. The 5-min vacuum application resulted in a reduction of overrun and air bubbles size, whereas ice cream viscosity increased. Opposite outcomes were found for the sample treated with vacuum for 30 min, which also showed a significant fat globule size reduction (<3.0 μm). Sensory analysis revealed that the use of vacuum improved sweetness, milky and creamy sensations regardless the treatment times. 相似文献