A5073165405- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Synthesis and Characterization of Heterocyclic Compounds
- Pharmacological Receptor Mechanisms and Effects
- Click Chemistry and Applications
- Synthesis and biological activity
- Protein Kinase Regulation and GTPase Signaling
- Neuropeptides and Animal Physiology
- Calcium signaling and nucleotide metabolism
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Wnt/β-catenin signaling in development and cancer
- Nuclear Receptors and Signaling
- Advanced biosensing and bioanalysis techniques
- Quinazolinone synthesis and applications
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Graphene and Nanomaterials Applications
- Enzyme Production and Characterization
- Cellular transport and secretion
- Synthesis of β-Lactam Compounds
- Synthesis and Reactivity of Heterocycles
- Tryptophan and brain disorders
University of Trieste
2016-2025
GTx (United States)
2019
Università di Camerino
2012
University of Padua
2009-2010
University of Ferrara
2009
The P2X4 receptor is involved in immunological and inflammatory processes potent antagonists are potentially useful for therapeutic, investigational, diagnostic purposes. This Viewpoint summarizes the discovery of selective that bring researchers closer to obtaining valuable PET tracers studying receptor.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra human brain, leading to depletion dopamine production. Dopamine replacement therapy remains mainstay for attenuation PD symptoms. Nonetheless, potential benefit current pharmacotherapies mostly limited adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, A2A adenosine have emerged important...
Abstract Glycogen synthase kinase 3β (GSK‐3β) and casein 1δ (CK‐1δ) are emerging targets for the treatment of neuroinflammatory disorders, including Parkinson's disease. An inhibitor able to target these two kinases was developed by docking‐based design. Compound 12 , 3‐(7‐amino‐5‐(cyclohexylamino)‐[1,2,4]triazolo[1,5‐ a ][1,3,5]triazin‐2‐yl)‐2‐cyanoacrylamide, showed combined inhibitory activity against GSK‐3β CK‐1δ [IC 50 (GSK‐3β)=0.17 μ m ; IC (CK‐1δ)=0.68 ]. In particular, classical ATP...
Among the heterocyclic structures identified as potent human A3 (hA3) adenosine receptor's antagonists, we have demonstrated that new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of C2-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other receptor subytpes) but also overcome metabolic transformation furan ring into toxic intermediates. All synthesized [2-(para-substituted) phenyl]-pyrazolo-triazolo-pyrimidines...
Based on a screening of chemical library A2A adenosine receptor (AR) antagonists, series di- and tri-substituted adenine derivatives were synthesized tested for their ability to inhibit the activity enzyme casein kinase 1 delta (CK1δ) bind receptors (ARs). Some derivatives, here called “dual anta-inhibitors”, demonstrated good CK1δ inhibitory combined with high binding affinity, especially A2AAR. The N6-methyl-(2-benzimidazolyl)-2-dimethyamino-9-cyclopentyladenine (17, IC50 = 0.59 μM KiA2A...
The structure−activity relationship (SAR) of 1,2,4-triazolo[1,5-a]-1,3,5-triazine derivatives related to ZM241385 as antagonists the A2A adenosine receptor (AR) was explored through synthesis analogues substituted at 5 position. AR X-ray structure used propose a structural basis for activity and selectivity direct synthetic design strategy provide access solvent-exposed regions. Thus, we have identified point substitution attachment solubilizing groups enhance both aqueous solubility...
We propose a potential antiparkinsonian prodrug DP-L-A(2A)ANT (2) obtained by amidic conjugation of dopamine (1) via succinic spacer to new triazolo-triazine A(2A) adenosine receptor (AR) antagonist A(2A)ANT (3). The affinity 2 and its hydrolysis products-1, 3, dopamine-linker DP-L (4) A(2A)ANT-linker L-A(2A)ANT (5)-was evaluated for hA(1), hA(2A), hA(2B) hA(3) ARs rat striatum A(2A)ARs or D(2) receptors. patterns 2, 4 5 the stabilities 1 3 were HPLC analysis in human whole blood brain...
Fragment-Based Drug Discovery (FBDD) has become, in recent years, a consolidated approach the drug discovery process, leading to several candidates under investigation clinical trials and some approved drugs. Among these successful applications of FBDD approach, kinases represent class targets where this strategy demonstrated its real potential with kinase inhibitor Vemurafenib. In Kinase family, protein CK1 isoform δ (CK1δ) become promising target treatment different neurodegenerative...
Riluzole, approved by the US Food and Drug Administration (FDA) in 1995, is most widespread oral treatment for fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS). The drug, whose mechanism of action still obscure, mitigates progression illness, but unfortunately with only limited improvements. Herein we report first demonstration, using a combination computational vitro studies, that riluzole an ATP-competitive inhibitor protein kinase CK1 isoform δ, IC50 value 16.1 μm....
The application of both structure- and ligand-based design approaches represents to date one the most useful strategies in discovery new drug candidates. In present paper, we investigated how docking-driven conformational analysis can improve predictive ability 3D-QSAR statistical models. With use crystallographic structure complex with high affinity antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol), revisited a general pharmacophore...
Recent studies have highlighted the key role of Casein kinase 1 δ (CK1δ) in development several neurodegenerative pathologies, such as Alzheimer's disease (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS). So far, CK1δ inhibitors are noncovalent ATP competitive ligands no drugs currently available for this molecular target, hence interest developing new inhibitors. The study aims to identify able bind enzyme; by a dual approach silico/in vitro, virtual screening has been...
Nowadays, in medicinal chemistry adenosine receptors represent some of the most studied targets, and there is growing interest on different receptor (AR) subtypes. The AR subtypes selectivity highly desired development potent ligands to achieve therapeutic success. So far, very few ligand-based strategies have been investigated predict selectivity. In present study, we carried out a novel application multilabel classification approach by combining our recently reported autocorrelated...