A5056613970- Redox biology and oxidative stress
- Parasites and Host Interactions
- Enzyme function and inhibition
- Histone Deacetylase Inhibitors Research
- Helminth infection and control
- Glutathione Transferases and Polymorphisms
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- Trace Elements in Health
- Parasite Biology and Host Interactions
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Peroxisome Proliferator-Activated Receptors
- Amino Acid Enzymes and Metabolism
- Heat shock proteins research
- Chemical Reaction Mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Pharmacological Effects and Toxicity Studies
- Cancer-related Molecular Pathways
- Research on Leishmaniasis Studies
- Sulfur Compounds in Biology
- Organoselenium and organotellurium chemistry
- Inflammatory mediators and NSAID effects
- Click Chemistry and Applications
- Cancer Mechanisms and Therapy
National Research Council
2016-2025
Institute of Cell Biology and Neurobiology
2016-2025
Uppsala University
2017
Sapienza University of Rome
2010-2016
Istituto Pasteur
2011-2015
University of L'Aquila
2008
University of Milan
2008
University of Naples Federico II
2008
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed our immunohistochemistry studies on HDAC6 overexpression in tissues. We herein developed series of novel hHDAC6 inhibitors, having low inhibitory potency over hHDAC1 and hHDAC8, as potential pharmacological tools for treatment. Their was combined vitro vivo toxicity. Structural analysis 6h structure–activity...
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...
Schistosomiasis is the second most widespread human parasitic disease. It principally treated with one drug, praziquantel, that administered to 100 million people each year; less sensitive strains of schistosomes are emerging. One appealing drug targets against schistosomiasis thioredoxin glutathione reductase (TGR). This natural chimeric enzyme a peculiar fusion glutaredoxin domain selenocysteine (U)-containing domain. Selenocysteine located on flexible C-terminal arm usually disordered in...
Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report development a series spiroindoline-based HDAC6 isoform-selective based on X-ray crystal studies hit 6a. We identified compound 6j most potent selective hHDAC6 inhibitor series. Biological investigation compounds 6b, 6h, demonstrated their antiproliferative activity against several cancer cell lines. Western blotting indicated that...
The chemical analysis of the sponge Dysidea avara afforded known sesquiterpene quinone avarone, along with its reduced form avarol. To further explore role thiazinoquinone scaffold as an antiplasmodial, antileishmanial and antischistosomal agent, we converted avarone into derivative thiazoavarone. semisynthetic compound, well natural metabolites avarol, were pharmacologically investigated in order to assess their antiparasitic properties against sexual asexual stages Plasmodium falciparum,...
Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by Platyhelminthes genus Schistosoma. Schistosomes are only trematodes to have evolved sexual dimorphism constant pairing with a male essential for maturation female. Pairing required full development two major female organs, ovary vitellarium that involved in production different cell types such as oocytes vitellocytes, which represent core elements whole egg machinery. Sexually...
The p53 signalling pathway, which controls cell fate, has been extensively studied due to its prominent role in tumor development. pathway includes the supressor protein p53, vertebrate paralogs p63 and p73, their negative regulators MDM2 MDM4. p53/p63/p73-MDM system is ancient can be traced all extant animal phyla. Despite this, correct phylogenetic trees including both invertebrate species of p53/p63/p73 MDM families have not published. Here, we examined evolution family with particular...
Schistosomiasis (also known as bilharzia) is a neglected tropical disease caused by platyhelminths of the genus Schistosoma. The endemic in and subtropical areas world where water infested intermediate parasite host, snail. More than 800 million people live more 200 are infected require treatment. Praziquantel (PZQ) drug choice for schistosomiasis treatment transmission control being safe very effective against adult worms all clinically relevant Schistosoma species. Unfortunately, it...
Novel anti-schistosomal multi-stage drugs are needed because only a single drug, praziquantel, is available for the treatment of schistosomiasis and poorly effective on larval juvenile stages parasite. Schistosomes have complex life-cycle multiple developmental in intermediate definitive hosts. Acetylation deacetylation histones play pivotal roles chromatin structure regulation transcription eukaryotic cells. Histone deacetylase (HDAC) inhibitors modulate acetylation several other proteins...
Serine hydroxymethyltransferases (SHMTs) play an essential role in one-carbon unit metabolism and are used biomimetic reactions. We determined the crystal structure of free (apo) pyridoxal-5'-phosphate-bound (holo) SHMT from Methanocaldococcus jannaschii, first a hyperthermophile, archaea domain life that uses H₄MPT as cofactor, at 2.83 3.0 Å resolution, respectively. Idiosyncratic features were observed likely to contribute stabilization. At dimer interface, C-terminal region folds unique...
Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide caused by Platyhelminthes of the genus Schistosoma . The treatment schistosomiasis relies on long-term application single safe drug, praziquantel (PZQ). Unfortunately, PZQ very effective adult parasites and poorly larval stage immature juvenile worms; this can partially explain re-infection in endemic areas where patients are likely to host at different developmental stages...
Schistosomiasis is the most significant neglected tropical parasitic disease caused by helminths in terms of morbidity and mortality helminths. In this work, we present antischistosomal activity against Schistosoma mansoni a rationally selected small set thiazinoquinone derivatives, some which were previously found to be active Plasmodium falciparum others synthesized ad hoc. The effects on larvae, juvenile, adult parasite viability as well egg production development investigated, resulting...
Schistosomiasis is one of the most devastating neglected tropical parasitic diseases caused by trematodes genus Schistosoma. Praziquantel (PZQ) today only drug used in humans and animals for treatment schistosomiasis but unfortunately it poorly effective on larval juvenile stages parasite. Therefore, urgent discovery new targets compounds. We have recently showed that anti-anginal perhexiline maleate (PHX) very active multiple developmental Schistosoma mansoni vitro. It well known PHX...
Parasitic diseases cause significant global morbidity and mortality particularly in the poorest regions of world. Schistosomiasis, one most widespread neglected tropical diseases, affects more than 200 million people worldwide. Histone deacetylase (HDAC) inhibitors are prominent epigenetic drugs that being investigated treatment several including cancers parasitic diseases. Schistosoma mansoni HDAC8 (SmHDAC8) is highly expressed all life cycle stages parasite, selective inhibition required...