A5022792778- Computational Drug Discovery Methods
- melanin and skin pigmentation
- Biochemical Analysis and Sensing Techniques
- Phytochemicals and Antioxidant Activities
- Enzyme function and inhibition
- Microbial Natural Products and Biosynthesis
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Catalytic Reactions
- Alzheimer's disease research and treatments
- Synthesis and biological activity
- Parkinson's Disease Mechanisms and Treatments
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Click Chemistry and Applications
- Antimicrobial Peptides and Activities
- Metabolomics and Mass Spectrometry Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Adrenal Hormones and Disorders
- Neuropeptides and Animal Physiology
- Stress Responses and Cortisol
- Phenothiazines and Benzothiazines Synthesis and Activities
- Viral Infections and Immunology Research
- Dermatological and Skeletal Disorders
- Technology Assessment and Management
University of Milan
2022-2025
University of Messina
2019-2023
University of Vienna
2019
University of Parma
1994
Azienda Ospedaliero Universitaria San Giovanni Battista
1960
This comprehensive review, covering 2021-2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis functionalization coumarins have advanced with innovative strategies. enabled incorporation diverse functional fragments or construction supplementary cyclic architectures, thereby biological physico-chemical properties compounds obtained were enhanced. unique...
Clinical and electrophysiological signs of peripheral neuropathy were found in 10 46 patients (21.7%) with primary Sjögren9s syndrome, symmetric polyneuropathy seven (mainly sensory five, mainly autonomic two), neuronopathy two patients, mononeuropathy multiplex one patient. Peripheral was the presenting manifestation five (10.9%). Onset disease after 50 years significantly more common group (six seven) than non-neuropathic syndrome (14 36; p = 0.034). No other difference clinical or...
Proanthocyanidins (PACs), the predominant constituents within Grape Seed Extract (GSE), are intricate compounds composed of interconnected flavan-3-ol units. Renowned for their health-affirming properties, PACs offer a shield against spectrum inflammation associated diseases, such as diabetes, obesity, degenerations and possibly cancer. While monomeric dimeric undergo some absorption gastrointestinal tract, larger oligomeric polymeric counterparts not bioavailable. However, higher molecular...
The inhibition of tyrosinase (Ty, EC 1.14.18.1) represents an efficient strategy decreasing melanogenesis and skin hyperpigmentation. A combination crystallographic docking studies on two different tyrosinases, that from Bacillus megaterium (TyBm) a mushroom (TyM), has contributed to increasing our knowledge about their structural information translating the most druggable human Ty (TyH) isozyme. In particular, we designed synthesized series 1-(4-fluorobenzyl)piperazine...
Background—Aggressive solid tumors are commonly characterized by both basic intracellular pH and acidic extracellular pH, which increase cell survival proliferation. As carbonic anhydrases IX/XII involved in this regulation, their inhibition is an appealing approach cancer therapy, avoiding Substituted coumarins selective non-classical CA IX XII inhibitors. Methods—In study, new 7-hydroxycoumarinamides were synthesized assayed for antiproliferative activity. Results—All of the coumarinamides...
A series of 1-(4-sulfamoylbenzoyl)piperidine-4-carboxamides deriving from substituted piperazines/benzylamines was designed, synthesized, and tested on human carbonic anhydrase (hCA). The inhibitory activity the new sulfonamides analyzed using acetazolamide (AAZ) as a standard inhibitor against hCA I, II, IX, XII. Several showed both at low nanomolar concentrations selectivity cytosolic II isoform, same trend observed tumor-associated IX benzenesulfonamido carboxamides 11 15 were most potent...
Parkinson's disease is one of the most common neurodegenerative disorders in elderly age. One mechanisms involved neurodegeneration appears related to aggregation presynaptic protein alpha synuclein (α-syn) into toxic oligomers and fibrils. To date, no highly effective treatment currently available; therefore, there an increasing interest search new therapeutic tools. The modulation α-syn represents emergent promising disease-modifying strategy for reducing or blocking process. Herein, by...
Parkinson's disease (PD) is characterized by the death of dopaminergic neurons. The common histopathological hallmark in PD patients formation intracellular proteinaceous accumulations. main constituent these inclusions alpha-synuclein (α-syn), an intrinsically disordered protein that pathological conditions creates amyloid aggregates lead to neurotoxicity and neurodegeneration. goal our study was optimize previously identified α-syn aggregation inhibitors 5-(4-pyridinyl)-1,2,4-triazole...
The interaction of an equilibrium mixture monomeric and aggregated cationic trans-5,15-bis(N-methylpyridinium-4-yl)-10,15-bis-diphenylporphine (t-H2Pagg) chloride salt with human serum albumin (HSA) has been investigated through UV/Vis absorption, fluorescence emission, circular dichroism resonant light scattering techniques. spectroscopic evidence reveals that both the t-H2Pagg its aggregates bind instantaneously to HSA, leading formation a tight adduct in which porphyrin is encapsulated...
Abstract Melanogenesis controls the formation of melanin pigment whose overproduction is related to various hyperpigmentary disorders in humans. Tyrosinase a type‐3 copper enzyme involved rate limiting step synthesis, therefore its inhibition could represent an efficient way for development depigmenting agents. In this work, combination pharmacophore and docking‐based studies has been employed screen two in‐house 3D compound databases containing about 2,000 molecules from natural synthetic...
Tyrosinase is a type-3 copper protein involved in the biosynthesis of melanin pigments; therefore, inhibition its enzymatic activity represents promising strategy for treatment hyperpigmentation-related disorders. To address this point, we previously designed class 4-(4-fluorobenzyl)piperazin-1-yl-based compounds, which proved to be more active inhibitors against tyrosinase from mushroom Agaricus bisporus than positive control kojic acid. Herein, report synthesis further series...
A small series of hydrazonobenzenesulfonamides was designed, synthesized and studied for their human carbonic anhydrase (hCA) inhibitory activity. The compounds were evaluated against hCA I, II, IX XII isoforms using acetazolamide (AAZ) as the standard inhibitor. Various hydrazonosulfonamide derivatives showed activity at low nanomolar levels with selectivity cytosolic II isoform, well transmembrane, tumor-associated enzymes XII. most potent selective hydrazones 8, 9, 10, 11, 19 24 docked...
Computer aided drug-design methods proved to be powerful tools for the identification of new therapeutic agents. We employed a structure-based workflow identify inhibitors targeting mTOR kinase at rapamycin binding site. By combining molecular dynamics (MD) simulation and pharmacophore modelling, simplified hypothesis was built starting from FKBP12-rapamycin-FRB ternary complex retrieved RCSB Protein Data Bank (PDB code 1FAP). Then, obtained model used as filter screen ZINC biogenic...
There is a considerable attention for the development of inhibitors tyrosinase (TYR) as therapeutic strategy treatment hyperpigmentation disorders in humans. Continuing our efforts to identify TYR inhibitors, we describe design, synthesis and pharmacophore exploration new small molecules structurally characterized by presence 4-fluorobenzylpiperazine moiety key pharmacophoric feature inhibition from Agaricus bisporus (AbTYR). Our investigations resulted discovery competitive inhibitor...
Drug-induced cardiotoxicity represents one of the most critical safety concerns in early stages drug development. The blockade human ether-à-go-go-related potassium channel (hERG) is frequent cause cardiotoxicity, as it associated to long QT syndrome which can lead fatal arrhythmias. Therefore, assessing hERG liability new drugs candidates crucial avoid undesired cardiotoxic effects. In this scenario, computational approaches have emerged useful tools for development predictive models able...
Amongst drug resistant Gram-positive bacteria,
The lipoteichoic acid (LTA) biosynthesis pathway has emerged as a promising antimicrobial therapeutic target. Previous studies identified the 1,3,4 oxadiazole compound 1771 an LTA inhibitor with activity against Gram-positive pathogens. We have succeeded in making six derivatives and, through subsequent hit validation, incorporation of pentafluorosulfanyl substituent central enhancing activity. Our newly described derivative, 13, showed 16- to 32-fold increase compared when tested cohort...
The search for new drugs fulfilling One Health and Green Chemistry requirements is an urgent call. Here, the first time, we envisaged developing SAHA analogues by starting from cashew nutshell liquid (CNSL) agro-industrial waste employing a metathesis approach. This sustainable combination (comprising principles #7 #9) allowed straightforward synthesis of compounds 13–20. All them were found to not be toxic on HepG2, IMR-32, L929 cell lines. Then, their potential against major human animal...