1,721,078 research outputs found
Histone deacetylase inhibitors in the treatment of cancer: overview and perspectives
No full textHistone deacetylase inhibitors (HDACis) are one of the last frontiers in pharmaceutical research. Several classes of HDACi have been identified. Although more than 20 HDACi are under preclinical and clinical investigation as single agents and in combination therapies against different cancers, just two of them were approved by the US FDA: Zolinza (R) and Istodax (R), both licensed for the treatment of cutaneous T-cell lymphoma, the latter also of peripheral T-cell lymphoma. Since HDAC enzymes act by forming multiprotein complexes (clusters), containing cofactors, the main problem in designing new HDACi is that the inhibition activity evaluated on isolated enzyme isoforms does not match the in vivo outcomes. In the coming years, the research will be oriented toward a better understanding of the functioning of these protein complexes as well as the development of new screening assays, with the final goal to obtain new drug candidates for the treatment of cancer
Ionic Liquid as a Suitable Phase for Multistep Parallel Synthesis of an Array of Isoxazolines
No full text(Equation presented) A parallel array of isoxazoline diamides was prepared using an ionic liquid [bmim][BF4] as the phase where a three-step procedure (Schotten-Baumann, 1,3-dipolar cycloaddition, ester amidation with Me3Al) was carried out. At the end, selective extraction of the final products with diethyl ether allowed simple isolation of the 16 components of the array (Syncore technology)
Solid-phase synthesis of conformationally constrained peptidomimetics based on a 3,6-disubstituted 1,4-diazepan-2,5-dione core
No full textStarting from a Cl-trytyl linked hydroxylamine, a hydroxamic dipeptide having serine in the second position was prepared by using DMTMM as the coupling agent. Mitsunobu cyclization carried out under microwave heating gave very good yields of a 3,6-disubstituted-perhydro-diazepin-2,5-dione. This heterocycle can be used as a new platform for combinatorial chemistry or as a constraint to rigidify a small peptide
Colorimetric tools for solid-phase organic synthesis
No full textOne of the unresolved problems of solid-phase organic synthesis (SPOS) is the availability of general and rapid methods to monitor the transformation of functional groups present in molecules supported on insoluble supports. Color tests, far from providing the ultimate solution, may help in detection (and sometimes in quantification) of different functional groups. In this short review, we have collected most of the methods available and applied in SPOS with an Experimental Section that describes the procedure we have successfully applied to bead analyses in our laboratories
A simple procedure for the transformation of L- Glutamic acid into the corresponding g-aldehyde
No full text2-Dibenzylamino-5-oxopentanoic acid benzyl ester has been obtained in good yields by complete benzylation of L-glutamic acid in NaOH and Na2CO3, selective reduction of the gamma-ester into alcohol with DIBAL and further transformation into aldehyde using Swern oxidation. The overall three-step procedure from Glu gave aldehyde in 49% yield
Sensible improvements induced by ionic liquids in the reaction of modified carbasugars with bases for the building of constrained carbanucleosides
No full textStarting from racemic 4-hydroxy-4-methyl-2-cyclopentenone, a family of enantiopure carbanucleosides locked in the northern conformation has been synthesized. The use of ionic liquids was determinant in the last step resulting in a tangible increase of the yields and dramatic reduction of reaction times and volumes of organic solvents. To our knowledge, this is the first example of the use of ionic liquids in the coupling of carbasugars with heterocyclic bases
Co-Crystalline Phases of Syndiotactic Polystyrene with Azelaic Acid Molecules of Pharmaceutical Interest
No full textSorption of dicarboxylic acid molecules of pharmaceutical interest such as azelaic acid (AzA), in syndiotactic polystyrene (sPS) films presenting δ and ε nanoporous crystalline structure, is reported. Fourier Transform Infrared (FTIR), Polarized FTIR and Wide-Angle X-ray diffraction (WAXD) patterns on axially oriented sPS films has been performed to verify their sorption in crystalline lattices resulting in the formation of co-crystalline (CC) phases. Experimental evidence provides that AzA molecules can be included in the crystalline nanochannels of ε phase both as isolated and hydrogen-bonded molecules whereas they are only dissolved in the amorphous phase of δ samples
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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