A5069128525- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Eicosanoids and Hypertension Pharmacology
- Analytical Chemistry and Chromatography
- Adipose Tissue and Metabolism
- Ion channel regulation and function
- Inflammatory mediators and NSAID effects
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cholinesterase and Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Bone health and treatments
- Synthesis and biological activity
- Chemical Synthesis and Analysis
- Enzyme Catalysis and Immobilization
- Chemical Synthesis and Reactions
- Enzyme function and inhibition
- Drug Transport and Resistance Mechanisms
- Molecular spectroscopy and chirality
- Inorganic and Organometallic Chemistry
- Pharmacogenetics and Drug Metabolism
- Neuroscience and Neuropharmacology Research
University of Bari Aldo Moro
2016-2025
Istituto di Metodologie Chimiche
2014
Institute of Crystallography
2014
Istituto di Farmacologia Traslazionale
2012
University of L'Aquila
2008
University of Milan
2005-2008
University of Naples Federico II
2008
Instituto di Biofisica
2002-2005
Inserm
2005
Université de Lille
2005
The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of glucose and lipid metabolism. They activated by natural ligands, such as fatty acids, also targets synthetic antidiabetic hypolipidemic drugs. By using cell-based reporter assays, we studied the transactivation activity two enantiomeric ureidofibrate-like derivatives. In particular, show that R-enantiomer, (R)-1, is a full agonist PPARgamma, whereas S-enantiomer, (S)-1, less potent partial agonist. Most...
Abstract Resveratrol, a modulator of several signaling proteins, can exert off‐target effects involving the peroxisome proliferator‐activated receptor (PPAR) transcription factors. However, evidence for direct interaction between this polyphenol and PPARs is lacking. Here, we addressed hypothesis that resveratrol its metabolites control aspects PPAR transcriptional activity through with PPARs. Bioaffinity chromatographic studies immobilized ligand‐binding domains (LBDs) PPARγ PPARα...
Abstract The peroxisome proliferator-activated receptors (PPARs) are nuclear involved in the regulation of metabolic homeostasis and therefore represent valuable therapeutic targets for treatment diseases. development more balanced drugs interacting with PPARs, devoid side-effects showed by currently marketed PPARγ full agonists, is considered major challenge pharmaceutical companies. Here we present a structure-based virtual screening approach that let us identify novel PPAR pan-agonist...
PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, serve as an alternative treatment for metabolic diseases. In this work, affinity-based bioassay was found be effective selecting from the dried extract of African plant (Diospyros bipindensis). Among ligands, we identified betulinic acid (BA), a compound already known its...
The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors regulating glucose and lipid metabolism. search for new PPAR ligands with reduced adverse effects respect to the marketed antidiabetic agents thiazolidinediones (TZDs) dual-agonists glitazars is highly desired. We report crystal structure activity of two enantiomeric forms a clofibric acid analogue, respectively complexed ligand-binding domain (LBD) PPARgamma, provide an explanation on...
Peroxisome proliferator-activated receptor γ (PPARγ) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized tested library novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing substituent on nitrogen TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, 8a-10a). Three compounds (1a, 1i, 3a) exhibited selectivity towards PPARγ were found to be weak moderate partial agonists. Surface Plasmon Resonance (SPR) results...
A new series of derivatives the PPARα/γ dual agonist 1 allowed us to identify ligand (S)-6 as a potent partial both PPARα and γ subtypes. X-ray studies in PPARγ revealed two different binding modes canonical site. However, was also able bind an alternative site demonstrated by transactivation assay presence antagonist supported from docking experiments. This compound did not activate PPARγ-dependent program adipocyte differentiation inducing very less severe lipid accumulation compared...
A series of benzoxazole-based amides and sulfonamides were synthesized evaluated for their human peroxisome proliferator-activated receptor (PPAR)α PPARγ activity. All tested compounds showed a dual antagonist profile on both PPAR subtypes; based transactivation results, seven selected to test in vitro antiproliferative activity panel eight cancer cell lines with different expression rates PPARα PPARγ. 3f was identified as the most cytotoxic compound, higher potency colorectal HT-29 HCT116....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecificity of the chloride ion channel: action chiral clofibric acid analogsGiancarlo Bettoni, Fulvio Loiodice, Vincenzo Tortorella, Diana Conte-Camerino, Mercede Mambrini, Ermanno Ferrannini, and Shirley H. BryantCite this: J. Med. Chem. 1987, 30, 8, 1267–1270Publication Date (Print):August 1, 1987Publication History Published online1 May 2002Published inissue 1 August...
ClC-Ka and ClC-Kb Cl(-) channels are pivotal for renal salt reabsorption water balance. There is growing interest in identifying ligands that allow pharmacological interventions aimed to modulate their activity. Starting from available ligands, we followed a rational chemical strategy, accompanied by computational modeling electrophysiological techniques, identify the molecular requisites binding blocking or an activating site on ClC-Ka. The major determinant distinguishes activators...
Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPARγ. The partial agonism of the S enantiomer seems be due its capability stabilize regions receptor allowing interaction with both coactivators corepressors as shown by fluorescence resonance energy transfer (FRET) assays. recruitment corepressor N-CoR1 responsive elements PPARγ regulated promoters was confirmed chromatin immunoprecipitation...
A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. calorimetric approach used to characterize PPARγ-ligand interactions, docking experiments X-ray studies were performed explain the observed potency efficacy. R-1 S-1 selected evaluate several aspects biological In an adipogenic assay, both enantiomers increased expression PPARγ target genes promoted differentiation 3T3-L1 fibroblasts adipocytes. vivo administration these compounds insulin...
Abstract A number of matrix metalloproteinases (MMPs), proteins important in the balance bone remodeling, play a critical role both cancer metastasis and turnover associated with presence cells bone. Here, we report synthesis biological evaluation new class MMP inhibitors characterized by bisphosphonate function as zinc binding group. Since group is also implicated osteoclast inhibition provides preferential affinity to apatite, molecules can be regarded bone‐seeking medicinal agents....
A few symptomatic drugs are currently available for Alzheimer's Disease (AD) therapy, but these molecules only able to temporary improve the cognitive capacity of patients if administered in first stages pathology. Recently, important advances have been achieved about knowledge this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward preparation being contemporaneously act on different pathological features. To date, inhibition...
In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized evaluated in silico, vitro vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects MCF7 HT29 cells. The excellent antiproliferative activity toward (IC50 =0.78±0.01 μM), =0.92±0.15 μM) K562 =47.25±1.24 cell lines, prompted us to further investigate best compound S2...
Monotargeting anticancer agents suffer from resistance and target nonspecificity concerns, which can be tackled with a multitargeting approach. The combined treatment HDAC inhibitors PPARγ agonists has displayed potential antitumor effects. Based on these observations, this work involves design synthesis of molecules that simultaneously HDAC. Several out 25 compounds inhibited HDAC4, six acted as dual-targeting agents. Compound 7i was the most potent, activity toward EC50 = 0.245 μM HDAC4...