A5019273560- Histone Deacetylase Inhibitors Research
- Cancer therapeutics and mechanisms
- Retinoids in leukemia and cellular processes
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Bioactive Compounds and Antitumor Agents
- Cancer Treatment and Pharmacology
- Heat shock proteins research
- Biochemical and Molecular Research
- Metabolism and Genetic Disorders
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Synthesis and biological activity
- ATP Synthase and ATPases Research
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Chronic Myeloid Leukemia Treatments
- Islamic Finance and Banking Studies
- Neuroblastoma Research and Treatments
- Platelet Disorders and Treatments
- Kruppel-like factors research
- PARP inhibition in cancer therapy
Alfasigma (Italy)
2018-2025
Sigma Tau (Italy)
2009-2023
Sigma-Tau (Switzerland)
1994-2015
University of Naples Federico II
2005-2010
Mario Negri Institute for Pharmacological Research
2005-2010
Institute of Genetics and Biophysics
2010
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni
2010
University of Rome Tor Vergata
1989-2010
Fondazione IRCCS Istituto Nazionale dei Tumori
2007
University of Salento
2005
Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates gave a new family 1,4,5-trisubstituted triazole carboxylic acid derivatives that showed high affinity toward Hsp90 associated cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement the resorcinol, moieties, and presence alkyl (secondary) amide position 4 ring were essential to get activity. Docking simulations...
Many severe human pathologies are related to alterations of the fine balance between histone acetylation and deacetylation; because not all such diseases involve hypoacetylation, but also hyperacetylation, compounds able enhance or repress activities acetyltransferases (HATs) could be promising therapeutic agents. We evaluated in vitro cell ability eleven natural polyisoprenylated benzophenone derivatives modulate HAT activity p300/CBP, an enzyme that plays a pivotal role variety cellular...
The inhibition of the long-term pressor effect ouabain may be useful for therapy essential hypertension. Here, first time, a selective inhibitor is described. In vitro, 17beta-(3-furyl)-5beta-androstane-3beta, 14beta, 17alpha-triol (PST 2238) displaced from its binding sites on purified sodium, potassium ATPase enzyme (Na-K ATPase) (IC50 1.7 x 10(-6) M) without interacting with other receptors involved in blood pressure regulation or hormonal control. cultured renal cells, incubation...
Abstract The aim of the present study was to identify specific αvβ3/αvβ5 integrin antagonists active on tumor-induced angiogenesis. To this purpose, in vitro integrin-binding assays were used screen a library conformationally constrained bicyclic lactam Arg-Gly-Asp–containing pseudopeptides. results identified ST1646 as high-affinity ligand for αvβ3 and αvβ5 integrins with negligible interacting α5β1 integrin. In all assays, equipotent or more potent than well-characterized c(RGDfV)...
Nonpeptidic chiral macrocycles were designed on the basis of an analogue suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification critical amino residues highly conserved in cap region HDACs guided design suberoyl-based macrocycles, which expected to bear a maximum common substructure required target whole HDAC panel. A nanomolar inhibitory profile was observed for several compounds, comparable, if not superior,...
Abstract Angiogenesis is one of the crucial events for cancer development and growth. Two members vascular endothelial growth factor (VEGF) family, VEGF-A placental (PlGF), which are able to heterodimerize if coexpressed in same cell, both required pathologic angiogenesis. We have generated a PlGF1 variant, named PlGF1-DE residues Asp72 Glu73 were substituted with Ala, unable bind activate VEGF receptor-1 but still VEGF. Here, we show that overexpression tumor cells by adenoviral delivery or...
A systematic study of medicinal chemistry aimed at identifying a new generation HDAC inhibitors, through the introduction thiol zinc-binding group (ZBG) and an amide-lactam in ω-position polyethylene chain vorinostat scaffold, allowed selection class potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, efficient synthetic approaches were used to synthesize library these derivatives, which then submitted screening for inhibition as well preliminary vitro assessment their...
Background/Objectives: Minimal hepatic encephalopathy (MHE) is a clinical condition characterized by neurological impairments, including brain inflammation, arising from the accumulation of toxic metabolites associated with liver dysfunction and leaky gut. This study investigated pharmacological activity new phytocomplex extracted red orange by-products (AL0042) using hydrodynamic cavitation consisting mixture pectin, polyphenols, essential oils. Methods: Preliminary in vitro studies...
In patients with Parkinson's disease (PD), constipation is common, and it appears in a prodromal stage before the hallmark motor symptoms. The present study aimed to investigate whether Velusetrag, selective 5‑HT4 receptor agonist, may be suitable candidate improve intestinal motility mouse model of PD. Five months old PrP human A53T alpha-synuclein transgenic (Tg) mice, which display severe along decreased colonic cholinergic transmission already at 3 months, were treated daily drug for 4...
Crohn’s and ulcerative colitis are common conditions associated with inflammatory bowel disease as well intestinal flora epithelial barrier dysfunction. A novel fermented Lactobacillus brevis (AL0035) herein assayed in a trinitro benzene sulfonic acid (TNBS)-induced mice model after oral administration significantly counteracted the body weight loss improves activity index histological injury scores. AL0035 decreased mRNA protein expression of different pro-inflammatory cytokines (TNFalpha,...
The novel atypical retinoid E-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926, 4) exhibited a potent antiproliferative activity on large panel of human tumor cells. Despite almost complete loss ability to activate RARs, the compound was an effective apoptosis inducer and surprisingly produced DNA damage, that likely contributes proapoptotic activity. Following oral administration, 4 well tolerated caused growth inhibition in ovarian carcinoma, A2780/DX, melanoma, MeWo, growing...
The synthesis and cytotoxic evaluation of 3-(alkyl)(alkyl-substituted)spiro[(dihydroimidazo-2,4-dione)-5,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)]derivatives are described. Evaluation these analogues against the MCF-7 human breast carcinoma SW 620 colon cell lines uncovered for most compounds a potency comparable to or greater than that doxorubicin. Compound 15 exhibited remarkable activity several other solid tumor lines. Interestingly, only partial cross-resistance compound in...
An NAD(P)H‐dependent reductase able to reduce a new class of cyclic unsaturated compounds named ketimines has been detected and purified 2500‐fold from pig kidney. Some molecular kinetic properties this enzyme have determined. The enzymatic reduction proceeds with classical ping‐pong mechanism some results suggest that the true substrate ketiminic structure is in equilibrium enaminic keto‐open forms. As previously described, arise deamination number sulfur‐containing amino acids, i.e. l...
A series of 3-substituted spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives were prepared using an easy synthetic route via condensation the 3-amino-3-(ethoxycarbonyl)-2,3-dihydrothieno[2,3-b]naphtho-4,9-dione system and amino acids followed by intramolecular lactamization. Amino containing alkyl aryl, linear cyclic, polar apolar, basic acid residues incorporated. Evaluation these analogues against MCF-7 human breast carcinoma SW 620 colon...