Search results for "DISCOVERY"
showing 10 items of 4119 documents
Chemical Characterization and Cytotoxic and Antioxidant Activity Evaluation of the Ethanol Extract from the Bulbs of Pancratium maritimun Collected i…
2023
P. maritimum L., belonging to the Amaryllidaceae family, is a species that grows on beaches and coastal sand dunes mainly on both sides of the Mediterranean Sea and Black Sea, the Middle East, and up to the Caucasus region. It has been largely investigated due to its several interesting biological properties. With the aim of providing new insights into the phytochemistry and pharmacology of this species, the ethanolic extract of the bulbs from a local accession, not previously studied, growing in Sicily (Italy), was investigated. This chemical analysis, performed by mono- and bi-dimensional NMR spectroscopy, as well as LC-DAD-MSn, allowed to identify several alkaloids, three of which were n…
Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides
2012
Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylati…
Identification of a new series of amides as non-covalent proteasome inhibitors
2014
Proteasome inhibition has emerged as an important therapeutic strategy for the treatment of multiple myeloma (MM) and some forms of lymphoma, with potential application in other types of cancers. 20S proteasome consists of three different catalytic activities known as chymotrypsin-like (ChT-L), trypsin-like (T-L), and, post-glutamyl peptide hydrolyzing (PGPH) or caspase-like (C-L), which are located respectively on the β5, β2, and β1 subunits of each heptameric β rings. Currently a wide number of covalent proteasome inhibitors are reported in literature; however, the less widely investigated non-covalent inhibitors might be a promising alternative to employ in therapy, because of the lack o…
Histaminanaloge, 28. Mitt. 2-Aryloxyalkyl- und 2-Aminoalkylhistamine
1987
Als Histaminderivate mit H1-affinitatsvermittelnden Strukturelementen in 2-Stellung des Imidazolrings wurden 2-Aryloxyalkyl- und 2-Aminoalkylhistamine sowie das racemische 2-(1-Phenylethyl)histamin dargestellt und auf Histamin-H1-agonistische Aktivitat untersucht. Histamine Analogues, XXVIII: 2-(Aryloxyalkyl)- and 2-(Aminoalkyl)histamines As histamine derivatives with structures at position 2 of the imidazole ring, which mediate H1-receptor affinity, 2-(aryloxyalkyl)- and 2-(aminoalkyl)histamines as well as racemic 2-(1-phenylethyl)histamine were prepared and tested for histamine H1-agonistic activity.
ChemInform Abstract: A Versatile Approach to CF3-Containing 2-Pyrrolidones by Tandem Michael Addition-Cyclization: Exemplification in the Synthesis o…
2016
The synthesis of new fluorinated pyrrolidones starting from unprotected amino esters and amino nitriles through a Michael addition-lactamization sequence is described. The resulting CF3 -containing building blocks, bearing a quaternary stereogenic center adjacent to the fluorinated group, have been converted into amino pyrrolidines that display potent β-secretase 1 (BACE1) inhibitory activity. This work constitutes an example of selective fluorination as a valid strategy for the modulation of physicochemical and biological properties of lead compounds in drug discovery.
Development and in vitro Evaluation of Antigen-Loaded Poly(amidoamine) Nanoparticles for Respiratory Epithelium Applications
2013
A poly(amidoamine) with disulfide linkages in the main chain and 4-hydroxybutyl and ω-carboxy-PEG groups (9:1 ratio) as side chains was prepared by Michael addition polymerization of cystamine bisacrylamide with 4-hydroxybutylamine and ω-carboxy-PEG-amine. To develop therapeutic protein formulations for improved delivery of antigen via the intranasal route, nanoparticles were prepared from this polymer by self-assembly with p24 or ovalbumin as the model proteins and CpG as the adjuvant. The nanoparticles incorporated the antigens and adjuvant from the feed solution with high efficiency (∼90 %) and have sizes of 112 and 169 nm, respectively, with low positive surface charge (∼+2 mV). Formula…
Aminobisphosphonate-activated γδ T cells in immunotherapy of cancer: doubts no more
2008
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …
Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening
2013
The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.
Imidazolsynthesen, 8. Mitt.: N-Substituierte Imidazole nach Weidenhagen
1976
Die Weidenhagen-Synthese N-unsubstituierter Imidazole aus α-substituierten Carbonylverbindungen 1, Aldehyden 3, wasrigem Ammoniak (4) und Kupfer(II)-salzen als Oxidationsmittel ist in Gegenwart primarer Amine 5 auch zur Darstellung N-substituierter Imidazole 6 geeignet. Weidenhagen Synthesis of N-Substituted Imidazoles The Weidenhagen synthesis of N-unsubstituted imidazoles from α-substituted carbonyl compounds 1, aldehydes 3, and aqueous ammonia (4) with copper (II) salts as oxidizing agents is also usable for the synthesis of N-substituted imidazoles 6 through the addition of primary amines 5.
Imidazolsynthesen, 10. Mitt. Zur selektiven Synthese N-substituierter Imidazol-4-äthanole
1977
Die Synthese N-substituierter Methoxyathylimidazole 5, 6 aus Aldehyden 1, 1-Hydroxy-4-methoxy-2-butanon (2), primaren Aminen 3 und Ammoniak (4) nach Weidenhagen liefert Gemische, in denen im GC die 1,4-Isomere 5 in der Regel deutlich uberwiegen. Aus diesen lassen sich durch Atherspaltung mit HJ die N-substituierten Imidazol-4-athanole 8 erhalten. Selective Synthesis of N-Substituted Imidazole-4-ethanols The synthesis of N-substituted methoxyethylimidazoles 5, 6 from aldehydes 1, 1-hydroxy-4-methoxy-2-butanone (2), primary amines 3, and ammonia (4), using the Weidenhagen cyclisation, yields mixtures in which, according to gc analysis, the 1,4-isomers 5 prevail. Ether cleavage with HI gives t…