A5072049747- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- Synthesis and Biological Evaluation
- Synthesis and biological activity
- Aldose Reductase and Taurine
- Enzyme Structure and Function
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cancer, Hypoxia, and Metabolism
- Acute Lymphoblastic Leukemia research
- Metabolism and Genetic Disorders
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Neuroscience and Neuropharmacology Research
- Mass Spectrometry Techniques and Applications
- Adenosine and Purinergic Signaling
- Pneumocystis jirovecii pneumonia detection and treatment
- Epigenetics and DNA Methylation
- Hormonal and reproductive studies
- Cardiac Ischemia and Reperfusion
- Nicotinic Acetylcholine Receptors Study
- Computational Drug Discovery Methods
- Chemical Reactions and Mechanisms
- Cancer therapeutics and mechanisms
- Cytomegalovirus and herpesvirus research
- Cancer-related gene regulation
University of Turin
2015-2025
Torino e-district
2015-2019
Istituto di Farmacologia Traslazionale
2014
Interface (United States)
2014
University of Bern
2005
University of Parma
2001-2003
University of Edinburgh
2003
Mario Negri Institute for Pharmacological Research
1998-2001
Bracco (Italy)
1993-1994
ENVIRON (United States)
1994
Abstract The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority cancers and its activity strongly contributes to tumour initiation progression. Inactivation PIN1 function conversely curbs growth cancer stem cell expansion, restores chemosensitivity blocks metastatic spread, thus providing rationale for therapeutic strategy based on inhibition. Notwithstanding, potent inhibitors are still missing from arsenal anti-cancer drugs. By...
Human dihydroorotate dehydrogenase ( hDHODH) catalyzes the rate-limiting step in de novo pyrimidine biosynthesis, conversion of to orotate. hDHODH has recently been found be associated with acute myelogenous leukemia, a disease for which standard intensive care not changed over decades. This work presents novel class inhibitors, are based on an unusual carboxylic group bioisostere 2-hydroxypyrazolo[1,5- a]pyridine, that designed starting from brequinar, one most potent inhibitors. A...
A new series of NSAIDs in which aspirin is joined by an ester linkage to furoxan moieties, with different ability release NO, were synthesized and tested for NO-releasing, antiinflammatory, antiaggregatory, ulcerogenic properties. Related furazan derivatives, aspirin, its propyl ester, γ-nitrooxypropyl taken as references. All the products described present antiinflammatory trend, maximized derivatives 12, 16, 17, they are devoid acute gastrotoxicity, principally due their nature, show...
// Cristian Taccioli 1, * , Giovanni Sorrentino 2, 3, Alessandro Zannini 3 Jimmy Caroli 1 Domenico Beneventano 4 Laura Anderlucci 5 Marco Lolli 6 Silvio Bicciato Giannino Del Sal Department of Life Sciences, University Modena and Reggio Emilia, 41125, Italy 2 Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste 34149, Dipartimento di Scienze della Vita, Università degli Studi Trieste, Ingegneria “Enzo Ferrari”, Statistiche, Bologna 40124, Drug Technology, Torino,...
Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known inhibit AKR1C3 a nonselective manner because of COX-off effects. Here we designed two analogues by proposing bioisosteric connection between the carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found selective manner. In particular, derivative highly...
AKR1C3 is an enzyme that overexpressed in several types of radiotherapy- and chemotherapy-resistant cancers. Despite a validated target for drug development, no inhibitor has been approved clinical use. In this manuscript, we describe our study new series potent AKR1C3-targeting 3-hydroxybenzoisoxazole based inhibitors display high selectivity over the AKR1C2 isoform low micromolar activity inhibiting 22Rv1 prostate cancer cell proliferation. silico studies suggested proper substituents to...
The hydroxytriazole system is here analysed and used to modulate acidic moieties present in lead compounds.
A new series of nonsteroidal antiinflammatory drugs (NSAIDs) obtained by linking ibuprofen to selected furoxan moieties and related furazans were synthesized tested for their antiinflammatory, antiaggregatory, ulcerogenic properties. All the derivatives are endowed with activity comparable that ibuprofen, but, unlike this drug, they display reduced acute gastrotoxicity. The masking ibuprofen-free carboxylic group seems be principally at basis topical irritant action. two 8 9 also trigger...
Dihydroorotate Dehydrogenase (DHODH) is a key enzyme of the de novo pyrimidine biosynthesis, whose inhibition can induce differentiation and apoptosis in acute myeloid leukemia (AML). DHODH inhibitors had shown promising vitro vivo activity on solid tumors, but their effectiveness was not confirmed clinical trials, probably because cancer cells exploited salvage pathway to survive. Here, we investigated antileukemic MEDS433, inhibitor developed by our group, against AML. Learning from...
Although coronaviruses (CoVs) have long been predicted to cause zoonotic diseases and pandemics with high probability, the lack of effective anti-pan-CoVs drugs rapidly usable against emerging SARS-CoV-2 actually prevented a promptly therapeutic intervention for COVID-19. Development host-targeting antivirals could be an alternative strategy control CoVs infections, as they quickly repositioned from one pandemic event another. To contribute these preparedness efforts, here we report on...
The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as possible AML therapeutic target. We recently discovered compound 1, potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation cell lines (THP1) the low nM range (EC50 32.8 nM) superior brequinar's phase I/II clinical trial 265 nM). Herein, we investigate 1 drug-like properties observing...
Resulting from hit-to-lead optimization, the aminopyrazole<bold>3a</bold>is a NIK inhibitor selective over 44 kinases.