A5026352630- Inflammatory mediators and NSAID effects
- Enzyme Catalysis and Immobilization
- Synthesis and Reactions of Organic Compounds
- Asymmetric Synthesis and Catalysis
- Synthesis of heterocyclic compounds
- Synthesis and Biological Evaluation
- Synthesis and Catalytic Reactions
- Microbial Metabolic Engineering and Bioproduction
- Synthesis and biological activity
- Fluorine in Organic Chemistry
- Analytical Chemistry and Chromatography
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Synthetic Organic Chemistry Methods
- Synthesis of β-Lactam Compounds
- Coordination Chemistry and Organometallics
- Pharmacogenetics and Drug Metabolism
- Ion channel regulation and function
- Chemical Synthesis and Reactions
- Receptor Mechanisms and Signaling
- Carbohydrate Chemistry and Synthesis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Estrogen and related hormone effects
- Neuroinflammation and Neurodegeneration Mechanisms
University of Bari Aldo Moro
2016-2025
John Wiley & Sons (United States)
2016
Istituto di Farmacologia Traslazionale
2015-2016
Bentham Science Publishers (China)
2013
Bentham Science Publishers (United Arab Emirates)
2013
Mario Negri Sud Foundation
2006
University of Wisconsin System
1992
University of Wisconsin–Madison
1988-1990
Aspirin affords cardioprotection through the acetylation of serine 529 in human cyclooxygenase-1 (COX-1) anucleated platelets, inducing a permanent defect thromboxane A 2 (TXA )–dependent platelet function. However, heterogeneity COX-1 suppression by aspirin has been detected cardiovascular disease and may contribute to failure prevent clinical events. The recent recognized capacity platelets make proteins de novo paves way identify new mechanisms involved variable response aspirin. We found...
3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a known selective cyclooxygenase-1 (COX-1) inhibitor, was used to design new series of 3,4-diarylisoxazoles in order improve its biochemical COX-1 selectivity and antiplatelet efficacy. Structure-activity relationships were studied using human whole blood assays for COX-2 inhibition vitro, results showed that the simultaneous presence 5-methyl (or -CF3), 4-phenyl, 5-chloro(-bromo or -methyl)furan-2-yl groups on isoxazole core essential...
The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands years. Nevertheless, COXs, particularly COX-1, linked to a plethora diseases such as cancer, heart failure, neurological and neurodegenerative only recently. COXs catalyze the first step in biosynthesis prostaglandins (PGs) are among most important mediators inflammation. All published structural work COX-1 deals with ovine isoenzyme, which is easier produce milligram-quantities than...
Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG leading cause of death for pediatric brain tumors due its infiltrative nature inoperability. Radiotherapy has only palliative effect on stabilizing symptoms.
Diffuse intrinsic pontine glioma (DIPG), now referred to as diffuse midline (DMG), is a highly aggressive pediatric cancer primarily affecting children aged 4 9 years old. Despite the research and clinical trials conducted identify possible treatment for DIPG, no effective drug currently available. These tumors often affect deep brain structures in young children, suggesting connection early development’s epigenetic regulation targets, possibly neural progenitor functions differentiation....
Background: Diffuse intrinsic pontine glioma [DIPG] is a fatal pediatric disease characterized by post-translational modification, replacement of lysine methionine in position 27 the N-terminal [H3K27M] tail histone 3 isoform-1 [H3.1] or isoform-3 [H3.3], respectively, expressed DIPG-36 and DIPG-50 cells. We investigated role cation channels DIPG cells for first time effects ATP-sensitive K+[KATP] TRPV1 channel modulators. Methods: Experiments were performed using “in vitro” cytotoxic assays...
Pediatric diffuse intrinsic pontine glioma (DIPG), classified under midline glioma, is a deadly tumor, with no effective treatments. The human mitochondrial protease hClpP potential DIPG therapeutic target, and this study describes the synthesis of two new series tetrahydropyridopyrimidindiones (THPPDs) as activators. Among tested compounds, we have identified 36 (THX6) that shows strong activation (EC50 = 1.18 μM) good cytotoxicity in ONC201-resistant cells (IC50 0.13 μM). Studying...
Background: The blood–brain barrier (BBB) plays an important role in regulating homeostasis of the central nervous system (CNS), and it is obstacle for molecules with a molecular weight higher than 500 Da seeking to reach it, making many drugs ineffective simply because they cannot be delivered where are needed. As result, crossing BBB remains rate-limiting factor brain drug delivery during treatment diseases, specifically tumors such as diffuse intrinsic pontine glioma (DIPG), highly...
Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in presence BPs is not known. To investigate this, effect zoledronic acid BP (ZOL) (3 × 10-8 to 5 10-4 M) treatment, on channels, cell proliferation, mineralization, has been investigated preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, rat/mouse native marrow-derived osteoblasts. In whole-cell patch clamp line- osteoblasts, ZOL potentiated...
3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol-4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition arylnitrile oxides to the enolate ion phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 °C. The corresponding 3-aryl-5-methyl-4-phenylisoxazoles easily generated dehydration/aromatization reaction under basic conditions 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines...
Cancer cells down-regulate different genes to give them a selective advantage in invasiveness and/or metastasis. The SLC25A26 gene encodes the mitochondrial carrier that catalyzes import of S-adenosylmethionine (SAM) into matrix, required for methylation processes, and is down-regulated cervical cancer cells. In this study we show due promoter hypermethylation, as mechanism promote cell survival proliferation. Furthermore, overexpression CaSki increases SAM availability promotes...
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are pharmacological targets non-steroidal anti-inflammatory drugs, used treat pain inflammation. Since it was reported that COX-1 is major player mediating brain inflammatory response, aim this study evaluate effects highly...