Search results for " Drug Discovery"
showing 10 items of 54 documents
Lavandula angustifolia Essential Oil and Linalool Counteract Social Aversion Induced by Social Defeat
2018
Many vegetable extracts, essential oils, and their main constituents are active on the Central Nervous System (CNS). In fact, they have been used as sedatives, hypnotics, or tranquilizers for their activity in treating CNS disorders. In this research, we studied the possible activities of Lavandula angustifolia (LA) essential oil and of its main constituent, linalool, as anti-stress compounds on anxiety and social interaction and their in vitro effects on proteins (pERK and PKA) involved in the transmission of the signal. An acute intraperitoneal injection of linalool (100 mg/kg) and of LA essential oil (200 mg/kg) reduced motor activity without any anxiolytic effect, but significantly incr…
The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes
2015
The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. Som…
Biochemical and chemical characterization of Cynara cardunculus L. extract and its potential use as co-adjuvant therapy of chronic myeloid leukemia
2017
Abstract Ethnopharmacological relevance Ancient mediterranean diet was characterized by consuming the spontaneous forms of Cynara cardunculus L. (CCL), commonly called artichoke. Cultivated and/or spontaneous forms of CC studies have demonstrated that methanol extract of CCL flower and/or cynaropicrin showed remarkable anti-proliferative activity in vitro models of leukocyte cancer cell. Aim of the study Chronic myeloid leukemia (CML) is associated with a reciprocal translocation of the long arms of chromosomes 9 and 22 generating the BCR/ABL fusion gene, translated in the p210 BCR/ABL oncoprotein kinase. This chimeric protein is the target of a kinase inhibitor, imatinib, but the developme…
3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity
2015
A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunctio…
Synthesis of isoindolo[1,4]benzoxazinone and isoindolo[1,5]benzoxazepine: two new ring systems of pharmaceutical interest
2015
Abstract Two new ring systems, isoindolo[1,4]benzoxazinone and isoindolo[1,5]benzoxazepine, were conveniently synthesized through cyclization of suitably substituted isoindole derivatives. Some of the new compounds exhibited antiproliferative activity against a wide range of human tumor cell lines with GI 50 mean values at low micromolar level (3.72–5.13 μM).
The role of cMET in non-small cell lung cancer resistant to EGFR-Inhibitors: Did we really find the target?
2014
Abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpr…
The Anti-amyloid Compound DO1 Decreases Plaque Pathology and Neuroinflammation-Related Expression Changes in 5xFAD Transgenic Mice
2018
Self-propagating amyloid-β (Aβ) aggregates or seeds possibly drive pathogenesis of Alzheimer's disease (AD). Small molecules targeting such structures might act therapeutically in vivo. Here, a fluorescence polarization assay was established that enables the detection of compound effects on both seeded and spontaneous Aβ42 aggregation. In a focused screen of anti-amyloid compounds, we identified Disperse Orange 1 (DO1) ([4-((4-nitrophenyl)diazenyl)-N-phenylaniline]), a small molecule that potently delays both seeded and non-seeded Aβ42 polymerization at substoichiometric concentrations. Mechanistic studies revealed that DO1 disrupts preformed fibrillar assemblies of synthetic Aβ42 peptides …
Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system
2015
The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Δ(5)-cholenoyl-amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3β-hydroxy-Δ(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin syste…
Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies
2015
Sara Capolla,1 Chiara Garrovo,2 Sonia Zorzet,1 Andrea Lorenzon,3 Enrico Rampazzo,4 Ruben Spretz,5 Gabriele Pozzato,6 Luis Núñez,7 Claudio Tripodo,8 Paolo Macor,1,9 Stefania Biffi2 1Department of Life Sciences, University of Trieste, 2Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Animal Care Unit, Cluster in Biomedicine (CBM scrl), Trieste, Italy; 4Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 5LNK Chemsolutions LLC, Lincoln, NE, USA; 6Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 7Bio-Target, Inc., University of C…
Preclinical Activity of New [1,2]Oxazolo[5,4-e]isoindole Derivatives in Diffuse Malignant Peritoneal Mesothelioma
2016
A series of 22 derivatives of the [1,2]oxazolo[5,4-e]isoindole system were synthesized through an efficient and versatile procedure that involves the annelation of the [1,2]oxazole moiety to the isoindole ring, producing derivatives with a wide substitution pattern. The structure-activity relationship indicates that the N-4-methoxybenzyl group appears crucial for potent activity. In addition, the presence of a 6-phenyl moiety is important and the best activity is reached with a 3,4,5-trimethoxy substituent. The most active compound, bearing both the structural features, was able to inhibit tumor cell proliferation at nanomolar concentrations when tested against the full NCI human tumor cell…