A5078908851- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Cancer-related gene regulation
- RNA modifications and cancer
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Marine Sponges and Natural Products
- Algal biology and biofuel production
- Signaling Pathways in Disease
- Genomics and Chromatin Dynamics
- Diabetes Treatment and Management
- Carcinogens and Genotoxicity Assessment
- Cholinesterase and Neurodegenerative Diseases
- Sirtuins and Resveratrol in Medicine
- FOXO transcription factor regulation
- Ubiquitin and proteasome pathways
- Psidium guajava Extracts and Applications
- Cancer Immunotherapy and Biomarkers
- Light effects on plants
University of Campania "Luigi Vanvitelli"
2013-2025
University of Naples Federico II
2007-2024
European Institute of Oncology
2020
Innsbruck Medical University
2020
Universität Innsbruck
2020
SDN Istituto di Ricerca Diagnostica e Nucleare
2016-2019
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2019
Naples Anesthesia & Physician Associates
2017
Institute of Genetics and Biophysics
2012-2014
Radboud University Nijmegen
2014
Empagliflozin (EMPA), a selective inhibitor of the sodium glucose co-transporter 2, reduced risk hospitalization for heart failure and cardiovascular death in type 2 diabetic patients EMPA-REG OUTCOME trial. Recent trials evidenced several cardio-renal benefits EMPA non-diabetic through involvement biochemical pathways that are still to be deeply analysed. We aimed evaluate effects on myocardial strain mice treated with doxorubicin (DOXO) analysis NLRP3 inflammasome MyD88-related resulting...
Purpose: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, mechanism(s) underlying their tumor selectivity poorly understood.Experimental Design and Results: Using gene expression analysis, we define a core set of six genes commonly regulated in acute myeloid leukemia (AML) blasts cell lines. MYC, most prominently modulated, is preferentially altered leukemia. Upon treatment, c-Myc acetylated at lysine 323 its decreases,...
In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed colocalize with the androgen receptor. We designed synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1–6 by coupling skeleton tranylcypromine 7, a known LSD1 inhibitor, 4-carboxy-4′-carbomethoxy-2,2′-bipyridine 8 5-carboxy-8-hydroxyquinoline 9, 2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid compounds able to simultaneously target both KDM...
Aims Hyperglycaemic conditions increase cardiac stress, a common phenomenon associated with inflammation, aging, and metabolic imbalance. Sodium–glucose cotransporter 2 inhibitors, class of anti‐diabetic drugs, showed to improve cardiovascular functions although their mechanism action has not yet been fully established. This study investigated the effects empagliflozin on cardiomyocytes following high glucose exposure, specifically focusing inflammatory responses. Methods results A...
Histone deacetylase (HDAC) inhibitors are promising new epi‐drugs, but the presence of both class I and II enzymes in HDAC complexes precludes a detailed elucidation individual functions. By using II‐specific inhibitor MC1568, we separated I‐ II‐dependent effects defined roles muscle differentiation cultured cells vivo . MC1568 arrests myogenesis by (i) decreasing myocyte enhancer factor 2D (MEF2D) expression, (ii) stabilizing HDAC4–HDAC3–MEF2D complex, (iii) paradoxically, inhibiting...
Pancreatic ductal adenocarcinoma (PDAC) represents an unmet clinical need due to the very poor prognosis and lack of effective therapy. Here we investigated potential domatinostat (4SC-202), a new class I histone deacetylase (HDAC) inhibitor, currently in development, sensitize PDAC first line standard gemcitabine (G)/taxol (T) doublet chemotherapy treatment.Synergistic anti-tumor effect combined treatment was assessed PANC1, ASPC1 PANC28 cell lines vitro as well on tumor spheroids...
Abstract Background The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that PRC1 complex member CBX2 is overexpressed solid tumors promotes cancer cell survival. However, its role leukemia still unclear. Methods We...
Cancer cells are characterized by uncontrolled cell proliferation and impaired bioenergetics. Sirtuins a family of highly conserved enzymes that play fundamental role in energy metabolism regulation. SIRT1, particular, drives many physiological stress responses metabolic pathways following nutrient deprivation. We previously showed SIRT1 activation using SCIC2.1 was able to attenuate genotoxic response senescence. Here, we report hepatocellular carcinoma (HCC) under glucose-deprived...
Bisphenol A (BPA) belongs to the class of chemicals known as endocrine disruptors and has been also involved in pathogenesis progression related cancer such breast prostate cancers. Here, we have investigated effect BPA human LNCaP cells non-transformed epithelial EPN cells. Our data showed that induces down regulation cyclin D1 expression upregulation cell cycle inhibitors p21 p27, leading arrest. Interestingly, found anti-proliferative response depends on a strong rapid activation...
Several evidence pointed out the role of epigenetics in Alzheimer's disease (AD) revealing strictly relationships between epigenetic and "classical" AD targets. Based on reported connection among histone deacetylases (HDACs) glycogen synthase kinase 3β (GSK-3β), herein we present discovery biochemical characterization first-in-class hit compound able to exert promising anti-AD effects by modulating targeted proteins low micromolar range concentration. Compound 11 induces an increase...
Cardiovascular disease (CVD) is the primary cause of mortality globally with a multifactorial etiology that involves epigenetics. Chromobox 3 (CBX3), major isoform heterochromatin protein 1, involved in intricate epigenetic mechanisms affecting congestive heart failure. In patients CVD affected by lung cancer risk, CBX3 exerts sophisticated mechanism action, suppressing proliferation, migration, and formation neointima vascular smooth muscle cells (VSMCs) Notch3 pathway, indicating potential...
A SAR study has been carried out around a modified scaffold of the natural product psammaplin obtained by replacing o-bromophenol unit an indole ring. series constructs were generated in short synthetic sequence that starts with functionalization C3 position situ nitrosoacrylate, and this is followed protection β-indole-α-oximinoesters, saponification, condensation symmetrical diamines, deprotection. Biochemical cellular characterization using U937 MCF-7 cells confirmed many these analogues...
Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms amenable large-scale production, thus overcoming the bottleneck biomass supply chemical activity characterization bioactive compounds. This characteristic has recently also prompted screening microalgae potential pharmaceutical Here, we show that monoacylglycerides (MAGs) purified from marine diatom Skeletonema marinoi have selective cytotoxic...
Coding control: Protein arginine methyltransferases (PRMTs) and histone lysine (HKMTs) are epigenetic enzymes involved in regulation of gene expression cellular processes. A new series histone/protein methyltransferase inhibitors based on the 1,5-diphenyl-1,4-pentadien-3-one scaffold is reported. The described compounds showed various degrees selectivity against tested PRMTs (PRMT1 CARM1) HKMT (SET7).
A group of benzamides related to anacardic acid amide CTPB with alkyl chains defined length were prepared by a five-step sequence starting from 2,6-dihydroxybenzoic acid, and their activities compared those reported for the HAT inhibitor (AA). The subset 4-cyano-3-trifluoromethylphenylbenzamides shorter exhibited similar that AA, as they behaved human p300 inhibitors, induced decrease in histone acetylation levels immortalized HEK cells, counteracted action HDAC SAHA MCF7 breast cancer...
Over the past years BARD1 (BRCA1-associated RING domain 1) has been considered as both a BRCA1 (BReast Cancer susceptibility gene 1, early onset) interactor and tumor suppressor mutated in breast ovarian cancers. Despite its role stable heterodimer with BRCA1, increasing evidence indicates that also BRCA1-independent oncogenic functions. Here, we investigate expression function human acute myeloid leukemias modulation by epigenetic mechanism(s) microRNAs. We show HDACi (histone deacetylase...
HDAC inhibitors (HDACi) are widely used in the clinic to sensitize tumorigenic cells for treatment with other anticancer compounds. The major drawback of HDACi is broad inhibition plethora HDAC-containing complexes. In acute promyelocytic leukemia (APL), repression by PML-RARα oncofusion protein mediated an complex that can be dissociated pharmacologic doses all trans retinoic acid (ATRA) inducing differentiation and cell death at expense side effects recurrence. We hypothesized...
Altered expression and activity of histone deacetylases (HDACs) have been correlated with tumorigenesis. Inhibitors HDACs (HDACi) induce acetylation non-histone proteins affecting gene expression, cell cycle progression, migration, terminal differentiation death. Here, we analyzed the regulation ARHGEF3, a RhoA-specific guanine nucleotide exchange factor, by HDACi MS275 (entinostat). is well-known benzamide-based HDACi, which induces monoblastic-like human histiocytic lymphoma line U937 to...
Abstract Chemical manipulations performed on 2‐methyl‐3‐carbethoxyquinoline ( 1 ), a histone acetyltransferase inhibitor previously identified by our research group and active at the sub‐millimolar/millimolar level, led to compounds bearing higher alkyl groups C2‐quinoline or additional side chains C6‐quinoline positions. Such displayed least threefold improved inhibitory potency toward p300 protein lysine activity; some of them decreased H3 H4 acetylation levels in U937 cells induced high...
// Mariarosaria Conte 1 , Carmela Dell'Aversana 2 Rosaria Benedetti Francesca Petraglia Annamaria Carissimo Valeria Belsito Petrizzi 3 Alfonso Maria D'Arco Ciro Abbondanza Angela Nebbioso and Lucia Altucci 1,2 Department of Biochemistry, Biophysics General Pathology, Seconda Università degli Studi di Napoli, vico L. De Crecchio, Naples, IT Institute Genetics Biophysics, IGB 'Adriano Buzzati-Traverso', Via P. Castellino, Division Onco-Hematology, Umberto I Hospital, via S. Francesco, Nocera...