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- Nata il 19/01/1983, a Firenze;
- Laureata presso l’Università degli Studi di Firenze in Farmacia con una tesi sperimentale in Chimica Farmaceutica dal titolo “Progettazione e sintesi di ligandi dei recettori adenosinici a struttura pirazolo[1’,5’:1,6]pirimido[4,5-d]piridazinonica” con una votazione di 110/110 e lode (2007);
- Titolare di borsa di studio per un anno (2008) presso il Dipartimento di Chimica con un progetto dal titolo “Inibitori dell’Anidrasi Carbonica (CA)”;
- Dottore di Ricerca in Chimica e Tecnologia del Farmaco con una tesi dal titolo “Sintesi e valutazione farmacologica di inibitori dell’elastasi dei neutrofili umani (HNE)” (2009-2012);
- Periodo all'estero durante il dottorato presso il Royal Collage of Surgeons in Ireland (RCSI) a Dublino. Titolo della ricerca “Applicazione della reazione di Henry e organocatalisi enantioselettiva su sistemi isossazolici” (2011);
- Dal 2012 al 2015 Titolare di assegno di ricerca dal titolo “Progettazione e sintesi di piccole molecole ad attività duale come inibitori delle PDE4 e M3 antagonisti” nell’ambito del progetto FABER, presso il Dipartimento di Neurofarba (responsabile del progetto Prof.ssa Maria Paola Giovannoni);
- Dal 2016 al 2019 Titolare di assegno di ricerca dal titolo “Progettazione, sintesi e caratterizzazione di derivati eterocicli come inibitori dell’elastasi dei neutrofili umani (HNE)” presso il Dipartimento di Neurofarba (responsabile del progetto Prof.ssa Maria Paola Giovannoni);
- Tiolare di una borsa di studio per un anno (2020) dal titolo “Progettazione, sintesi e caratterizzazione di derivati eterocicli come inibitori dell’elastasi dei neutrofili umani (HNE)” presso il Dipartimento di Neurofarba (responsabile del progetto Prof.ssa Maria Paola Giovannoni);
- Dal 1 Settembre 2021 al 31 agosto 2024, ricercatrice a tempo determinato di tipo a) presso il Dipartimento di Neurofarba, sezione Farmaceutica e Nutraceutica, settore concorsuale 03/D1, settore scientifico disciplinare CHIM/08.
Attività di ricerca
Legenda
Born 19/01/1983, in Florence;
- Graduated from the University of Florence in Pharmacy with an experimental thesis in Pharmaceutical Chemistry titled "Design and synthesis of adenosine receptor ligands with pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazinonic structure" with a mark of 110/110 cum laude (2007);
- Scholarship holder for one year (2008) at the Department of Chemistry with a project entitled "Carbonic Anhydrase (CA) Inhibitors";
- PhD in Medicinal Chemistry and Technology with a thesis entitled "Synthesis and pharmacological evaluation of human neutrophil elastase (HNE) inhibitors" (2009-2012);
- Period abroad during PhD at the Royal Collage of Surgeons in Ireland (RCSI) in Dublin. Research title "Application of the Henry reaction and enantioselective organocatalysis on isoxazolic systems" (2011);
- From 2012 to 2015 Holder of a research grant entitled "Design and synthesis of small molecules with dual activity as PDE4 inhibitors and M3 antagonists" as part of the FABER project, at the Department of Neurofarba (project leader Prof. Maria Paola Giovannoni);
- From 2016 to 2019 Holder of a research grant entitled "Design, synthesis and characterisation of heterocyclic derivatives as inhibitors of human neutrophil elastase (HNE)" at the Department of Neurofarba (project leader Prof. Maria Paola Giovannoni);
- Holder of a scholarship for one year (2020) entitled "Design, synthesis and characterisation of heterocyclic derivatives as inhibitors of human neutrophil elastase (HNE)" at the Department of Neurofarba (project leader Prof. Maria Paola Giovannoni);
- From 1 September 2021 to 31 August 2024, fixed-term researcher type a) at the Department of Neurofarba, Pharmaceutical and Nutraceutical Section (03/D1, scientific disciplinary sector CHIM/08).
Research topic
1. Human neutrophil elastase (HNE) inhibitors. This project is carried out in collaboration with the Department of Molecular Biology at the University of Montana. Human neutrophil elastase belongs to the serine protease family and is involved in various physiological processes such as inflammation, infection and tissue homeostasis. Compounds capable of inhibiting the activity of this enzyme represent great therapeutic potential, especially for diseases of the respiratory system. The most interesting products synthesised so far are N-benzoylindazole-structured. Many compounds in this new series have activity values in the nanomolar range and good selectivity against other proteases such as thrombin, chymotrypsin and urokinase. Studies on the mechanism of action have shown that they act as pseudo-irreversible competitive inhibitors. Over the years, many other monocyclic and bicyclic polyacylated scaffolds have been investigated, obtaining very interesting results that have allowed research to continue.
2. Formyl peptide receptor ligands (FPRs). Formylated peptide receptors (FPRs) belong to the G-protein-coupled receptor family and so far three different isoforms have been identified in humans (FPR1, FPR2 and FPR3). These receptors are expressed in most white blood cells and are therefore largely involved in the regulation of inflammatory processes. In this field, a large number of compounds with a pyridazinone structure have been designed, synthesised and tested at the Department of Molecular Biology at the University of Montana, which have proved capable of acting as agonists against FPRs, with activity in the submicromolar range. In particular, selective agonists for FPR1, for FPR2 and mixed FPR1/FPR2 agonists were obtained. Moreover, some of these compounds have been shown to stimulate chemotaxis at submicromolar concentrations.
3. Phosphodiesterase 4 (PDE4) inhibitors. Research on PDE4 was developed in collaboration with Chiesi Farmaceutici S.P.A with the aim of obtaining useful compounds for the treatment of COPD. This collaboration has led to a large number of quinoline-based products active in the nanomolar range currently being published.
4. Compounds with analgesic activity. Work on compounds with antinociceptive activity has been directed towards the synthesis of functionalised and heterocondensed pyridazinones. The results obtained by testing the products in various animal models (writing test, hot plate test, formalin test, etc.) are extremely interesting, taking into account that in some cases the compounds exhibit analgesic activity comparable to that of morphine and are orally active. The studies are conducted in collaboration with the Pharmacology and Toxicology Section of the Department of Neuropharmacology and the Istituto Superiore di Sanità and have highlighted the involvement of the adrenergic system in the mechanism of action of these compounds.
5. Adenosine receptor ligands. A project was developed in which tricyclic polythiazide structures that formally meet the basic requirements of the classical model of adenosine receptor ligands were designed and synthesised. The products were tested on human A1, A2A and A3 receptors at the Department of Pharmacy of the University of Pisa. Most of the compounds showed high selectivity of action towards the A1 receptor and high affinity with Ki values in the low nanomolar range. The most interesting compound shows an in vivo anti-amnesic effect at doses of 10 and 30 mg/Kg. The project continues to be active through collaboration with Prof. Graham of Cambridge University.
6. Other active research lines concern pannexin channel blockers (Panx-1) and benzodiazepine GABAa receptor ligands.