A5053944964- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Antimicrobial Resistance in Staphylococcus
- Synthesis and Catalytic Reactions
- Microbial Natural Products and Biosynthesis
- Bacteriophages and microbial interactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Click Chemistry and Applications
- Asymmetric Synthesis and Catalysis
- Synthesis and biological activity
- Sulfur-Based Synthesis Techniques
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Synthesis and Biological Evaluation
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Cancer therapeutics and mechanisms
- Adenosine and Purinergic Signaling
- Chemical Reaction Mechanisms
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- Antimicrobial Peptides and Activities
- Parkinson's Disease Mechanisms and Treatments
- Analytical Chemistry and Chromatography
- Bacterial biofilms and quorum sensing
University of Milan
2018-2025
The widespread emergence of antimicrobial resistance (AMR) is a serious threat to global public health and among Gram-positive cocci, Streptococcus pneumoniae constitutes priority in the list AMR-threatening pathogens. To counteract this fundamental problem, bacterial cell division cycle crucial proteins involved process emerged as novel attractive targets. FtsZ an essential protein, inhibitors, especially benzamide derivatives, have been exploited last decade. In work, we identified, for...
Abstract FtsZ is a crucial prokaryotic protein involved in bacterial cell replication. It recently arose as promising target the search for antimicrobial agents able to fight resistance. In this work, going on with our structure‐activity relationship (SAR) study, we developed variously 7‐substituted 1,4‐benzodioxane compounds, linked 2,6‐difluorobenzamide by methylenoxy bridge. Compounds exhibit antibacterial activities not only against multidrug‐resistant Staphylococcus aureus , but also...
Filamentous temperature-sensitive Z (FtsZ) is a prokaryotic protein with an essential role in the bacterial cell division process. It widely conserved and expressed both Gram-positive Gram-negative strains. In last decade, several research groups have pointed out molecules able to target FtsZ Staphylococcus aureus, Bacillus subtilis other strains, sub-micromolar Minimum Inhibitory Concentrations (MICs). Conversely, no promising derivatives active on Gram-negatives been found up now. Here, we...
Multidrug resistant Staphylococcus aureus is a severe threat, responsible for most of the nosocomial infections globally. This strain associated with 64% increase in death compared to antibiotic-susceptible strain. The prokaryotic protein FtsZ and cell division cycle have been validated as potential targets exploit general battle against antibiotic resistance. Despite discovery development several anti-FtsZ compounds, no inhibitors are currently used therapy. work further develops...
Parkinson's disease (PD) is characterized by dopaminergic nigrostriatal neurons degeneration and Lewy body pathology, mainly composed of α-synuclein (αSyn) fibrillary aggregates. We recently described that the neuronal phosphoprotein Synapsin III (Syn III) participates in αSyn pathology PD brains a permissive factor for aggregation. Moreover, we reported gene silencing Syn human transgenic (tg) mouse model at pathological stage, manifesting marked insoluble deposits striatal synaptic...
The conserved process of cell division in bacteria has been a long-standing target for antimicrobials, although there are few examples potent broad-spectrum compounds that inhibit this process. Most currently available acting on directed towards the FtsZ protein, self-assembling GTPase is central element machinery most bacteria. Benzodioxane-benzamides promising candidates, but poorly explored Gram-negatives. We have tested number these E. coli and found many them significantly stabilized...
Chronic innate immune activation is a key hallmark of many neurological diseases and known to result in the upregulation GPR84 myeloid cells (macrophages, microglia, monocytes). As such, can potentially serve as sensor proinflammatory responses. To assess utility an imaging biomarker, we synthesized 11C-MGX-10S 11C-MGX-11S via carbon-11 alkylation for use positron emission tomography (PET) tracers targeting this receptor. In vitro experiments demonstrated significantly higher binding both...
The exploration of different reaction conditions aiming to obtain both 2,3-dihydro-1,4-benzoxathiine-2-yl derivatives and 2,3-dihydro-1,4-benzoxathiine-3-yl ones is reported. treatment 1,2-mercaptophenol with an organic base a specific 2-bromo acrylate results in solvent- substrate-dependent exclusive solvation O- S-anions, thus managing the regioselectivity.
FtsZ is an essential bacterial protein abundantly studied as a novel and promising target for antimicrobials. highly conserved among bacteria mycobacteria, it crucial the correct outcome of cell division process, responsible parent into two daughter cells. In recent years, benzodioxane-benzamide class has emerged very capable targeting both Gram-positive Gram-negative FtsZs. this study, we explored effect including substituent on ethylenic linker between main moieties antimicrobial activity...
2,6-difluorobenzamides have been deeply investigated as antibacterial drugs in the last few decades. Several 3-substituted-2,6-difluorobenzamides proved their ability to interfere with bacterial cell division cycle by inhibiting protein FtsZ, key player of whole process. Recently, we developed a novel family 1,4-tetrahydronaphthodioxane benzamides, having an ethoxy linker, which reached sub-micromolar MICs towards Gram-positive Staphylococcus aureus and Bacillus subtilis. A further...
1,4-Benzoxathiane, 2- or 3-substituted, is an important scaffold, and despite its presence in several therapeutic agents, it chemically unexploited. Furthermore, only a few examples literature report this moiety enantiopure form. Here, taking advantage to the formation of diastereomeric amides by using (S)-phenylethylamine, which show significant differences terms 1 H-nuclear magnetic resonance (NMR) spectra other physical chemical properties, we defined for first time absolute configuration...
Antibiotic resistance is spreading worldwide and it has become one of the most important issues in modern medicine. In this context, bacterial RNA degradation processing machinery are essential processes for viability that may be exploited antimicrobial therapy. Staphylococcus aureus, RnpA been hypothesized to main players these mechanisms. S. aureus able modulate mRNA complex with a ribozyme (rnpB), facilitating ptRNA maturation. Corresponding small molecule screening campaigns have...
(3-Methylene-2,3-dihydronaphtho[2,3-b][1,4]dioxin-2-yl)methanol was unexpectedly achieved as the main reaction product while applying a standard Johnson–Corey–Chaykovsky procedure to 2,3-dihydronaphtho[2,3-b][1,4]dioxine-2-carbaldehyde, aiming at obtaining corresponding epoxide. The structure of recovered compound confirmed through NMR and HRMS, melting point measured by DSC, organic purity assessed using HPLC. We hypothesized possible mechanism for obtainment this side product, which should...
In this work, we report the unexpected conversion of a pyridine derivative into corresponding N-benzylated pyridinium salt due to presence unreacted benzyl bromide in crude product. This transformation was observed at room temperature solvent-free environment and without any stirring. These interesting data show how salts can be formed mild conditions, avoiding high temperatures that could promote degradation desired