A5079136016- Aldose Reductase and Taurine
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Chemical Reactions and Isotopes
- Synthesis and Biological Evaluation
- Adenosine and Purinergic Signaling
- Thyroid Cancer Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Bioactive Compounds and Antitumor Agents
- Prenatal Substance Exposure Effects
- Cancer-related Molecular Pathways
- Biochemical effects in animals
- Cancer Cells and Metastasis
- Chemical Synthesis and Analysis
- Cannabis and Cannabinoid Research
- Lung Cancer Research Studies
- Enzyme function and inhibition
- Synthesis and pharmacology of benzodiazepine derivatives
- Synthesis of heterocyclic compounds
- Quinazolinone synthesis and applications
- Glioma Diagnosis and Treatment
- Neuroscience and Neuropharmacology Research
- Synthesis and Catalytic Reactions
University of Pisa
2016-2025
University of Ulster
2018
Technical University of Munich
2018
University of Kaiserslautern
2018
Nestlé (Switzerland)
2018
Universität Hamburg
2018
Technische Universität Berlin
2018
Woosuk University
2018
Abiogen Pharma (Italy)
2009
University of Cagliari
2008
Glioma stem-like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes a mesenchymal (MES) population as more malignant subtype. In this study, we identify FOXD1-ALDH1A3 signaling axis determinant of MES phenotype. The transcription factor FOXD1 is expressed predominantly patient-derived cultures enriched MES, but not proneural shRNA-mediated attenuation ablates their...
An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is great value because it provides opportunity for an exogenous control related process. Very often this aim can be pursued using high resolution structures complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, many other cases number factors, like protein flexibility or solvent effects, increase degree complexity ligand/protein...
2-Phenyl-pyrido[1,2-a]pyrimidin-4-one derivatives bearing a phenol or catechol moiety in position 2 were tested as aldose reductase (ALR2) inhibitors and exhibited activity levels the micromolar/submicromolar range. Introduction of hydroxy group 6 9 gave an enhancement inhibitory potency (compare 18, 19, 28, 29 vs 13 14). Lengthening 2-side chain to benzyl determined general reduction activity. The lack methylation hydroxyls inactive (10−12, 21, 22, 25−27) scarcely active (15, 17, 20)...
Adenosine modulates the immune system and inhibits inflammation via reduction of cytokine biosynthesis neutrophil functions. Drugs able to prevent adenosine catabolism could represent an innovative strategy treat inflammatory bowel disorders. In this study, effects 4-amino-2-(2-hydroxy-1-decyl)pyrazole[3,4-<i>d</i>]pyrimidine (APP; novel deaminase inhibitor), <i>erythro</i>-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA; standard dexamethasone were tested in rats with colitis induced by...
Glioblastoma multiforme (GBM) is the deadliest form of brain tumor. It known for its ability to escape therapeutic options available date thanks presence a subset cells endowed with stem-like properties and resist cytotoxic treatments. As cytosolic enzyme aldehyde dehydrogenase 1A3 turns out be overexpressed in these kinds cells, playing key role their vitality, treatments targeting this may represent successful strategy fight GBM. In work, we describe novel class imidazo[1,2-a]pyridine...
Novel N,N-disubstituted indol-3-ylglyoxylamides (1−56), bearing different combinations of substituents R1−R5, were synthesized and evaluated as ligands the translocator protein (TSPO), 18 kDa representing minimal functional unit "peripheral-type benzodiazepine receptor" (PBR). Most new compounds showed a nanomolar/subnanomolar affinity for TSPO stimulated steroid biosynthesis in rat C6 glioma cells with potency similar to or higher than that classic such PK 11195. Moreover, when vivo by...
We have studied the antitumoral activity of two new pyrazolo[3,4-d]pyrimidine compounds (CLM3 and CLM29) in primary papillary dedifferentiated thyroid cancer (DePTC) cells.The antiproliferative effect was tested DePTC cells obtained at reoperation from patients with recurrence tumor. The concentrations CLM3 CLM29 used vitro experiments were 1, 10, 30, 50 μm.Proliferation assays showed a significant reduction proliferation by CLM29, which 12% (the most potent compound) 10 μm, 43% 30 60% μm....
Aldehyde dehydrogenase 1A3 (ALDH1A3) belongs to an enzymatic superfamily composed by 19 different isoforms, with a scavenger role, involved in the oxidation of plethora aldehydes respective carboxylic acids, through NAD+-dependent reaction. Previous clinical studies highlighted high expression ALDH1A3 cancer stem cells (CSCs) correlated higher risk relapses, chemoresistance and poor outcome. We report on structural, biochemical, cellular characterization NR6, new selective inhibitor derived...
We have studied the antitumor activity of a novel cyclic amide, CLM94, with anti-vascular endothelial growth factor (VEGF) receptor-2 and antiangiogenic in primary anaplastic thyroid cancer (ATC) cells vitro vivo.CLM94 was tested: 1) two human cell lines (HMVEC-d, dermal microvascular cells; 8305C, undifferentiated cancer) at 0.001-100 μm; 2) ATC concentrations 10, 30, 50 3) an line (AF) CD nu/nu mice.CLM94 significantly inhibited VEGF epidermal receptor phosphorylation HMVEC-d proliferation...
Aldose reductase (AR) is an NADPH-dependent reductase, which acts on a variety of hydrophilic as well hydrophobic aldehydes. It currently defined the first enzyme in so-called polyol pathway, glucose transformed into sorbitol by AR and then to fructose NAD+-dependent dehydrogenase. An exaggerated flux through pathway (as can occur diabetes) with subsequent accumulation sorbitol, was originally proposed basic event aethiology secondary diabetic complications. For decades this has meant...
We have studied the antitumor activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) proposed for multiple signal transduction inhibition [including RET tyrosine kinase, epidermal growth factor receptor, and vascular endothelial (VEGF) receptor with antiangiogenic activity] in primary anaplastic thyroid cancer (ATC) cells, human cell line 8305C (undifferentiated cancer), an ATC-cell (AF).CLM3 was tested ATC cells at concentrations 5, 10, 30, 50 μM; AF 1, 50, or 100 CD nu/nu mice.CLM3...
In search for a novel chemotype to develop topoisomerase I (Top1) inhibitors, the pyrazolo[1,5-a]quinazoline nucleus, structurally related indenoisoquinoline system precursor of well-known Top1 poisons, was variously decorated (i.e., substituted phenyl ring at 2- or 3-position, protonable side chain 4- 5-position), affording number inhibitors with cleavage patterns common CPT and MJ-III-65. SARs data were rationalized by means an advanced docking protocol.
Two related inhibitors were flexibly docked into different conformers of aldose reductase. Although the overall binding topologies roughly matched, significant deviations are observed in subsequently determined crystal structures. Flexible redocking crystallographically protein achieves, however, perfect binding-position predictions.
A number of derivatives 4-amino-6-hydroxy-2-mercaptopyrimidine (5) were synthesized and biologically evaluated as A3 adenosine receptor (A3 AR) antagonists. The new compounds designed open chain analogues a triazolopyrimidinone derivative displaying submicromolar affinity for the AR, which had been previously identified using 3D database search. Substituents R, R′, R′′ attached to parent compound 5 chosen according factorial design stepwise lead optimization approaches, taking into account...