Claudia Vergelli

Biography

Claudia Vergelli graduated in Pharmaceutical Chemistry and Technology at the Pharmacy Faculty of the University of Florence in July 1997, with a vote 110 and Lode / 110, with an experimental thesis titled: "Synthesis, antiinocyte activity-structure correlations and study of mechanism of action of 4-amino-5-vinyl-3 (2H) -pyridazinones and related compounds. " In May 1998 she obtained her degree in Pharmacist Profession. From May 1998 to April 2000 he has been involved in scientific collaboration at the Department of Pharmaceutical Sciences of the University of Florence. In April 2003 he acquired the title of Doctor of Chemistry and Technology Research at the Department of Pharmaceutical Sciences with a thesis titled "Molecular Modifications of Nitraquazone analogs, potent and selective inhibitors of isoenzymes 4 and 5 of phosphodiesterases." From May 2003 to March 2006: has been the holder of a research grant at the Department of Pharmaceutical Sciences titled "Optimization of Molecular Flexibility Nitraquazone analogs, active as PDE4 inhibitors and potentially useful in asthma therapy of atopic dermatitis ". From April 2006 to March 2007 she has held a position as a Researcher at the Department of Pharmaceutical Sciences at the University of Florence: Research Program: "Optimizing the structure of active pyridazinone derivatives as PDE4 inhibitors, potentially useful in asthma and chronic obstructive bronchitis" for the CHIM08 scientific-disciplinary field.

Research Interest

r. Claudia Vergelli's research work started in 1998 at the Department of Pharmaceutical Sciences at the University of Florence. From the beginning, he focused on the synthesis and study of heterogeneous substances whose pharmacological activities have been studied . The obtained scientific results can be divided into 5 main topics that concern: 1. Analgesic compounds Work on antiinocyte compounds has been directed towards the synthesis of functionalized and heterohydrogenated pyridazinones. The elaboration of the research has led to the introduction of these alkylchilaminoalkylamino chain nuclei. The results obtained by testing the products in various animal models (writing test, hot plate test, formalin test, etc.) are extremely promising, given that in some cases the compounds exhibit comparable or even superior analgesic activity to that of the morphine. The most powerful molecules were also very active also by the oral route. The most interesting term among all synthesized products was active both in the tail flick test and in the hot plate test.to 2 yohimbine, and there has been a significant reversal of the analgesic effect, thus confirming an activity to 2 -agonist. Further studies conducted with Prazosin, at 1 -receptor, and subsequent binding studies have allowed us to affirm that the test compound is a 1 and a 2 agonist: in fact alloy at 1A is to 1B that in 2A with submicromolar values. These studies were conducted in collaboration with the Department of Clinical and Pre-Clinical Pharmacology of the University of Florence and with the Higher Institute of Health. 2. PDE4 inhibitors The project on PDE4 inhibitors, potentially useful for the treatment of many inflammatory and immune disorders such as asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, multiple sclerosis and so on, is now more active a decade ago and is currently working with Chiesi Farmaceutici in Parma. Recently, this research has led to the realization of mono and bicyclic systems containing the pyrazole ring and pyrimidinedione structures. Many of the new synthesized compounds show activity in the submicromolar range, and in some cases a good selectivity for other phosphodiesterases such as PDE3 and PDE5 and the Rolipram binding site (HARBS) responsible for most of the side effects of these products .to finding values ​​in the submicromolar range. 3. Ligands receptor formylated peptides Another research field that is under development is about the design and synthesis of ligands of formylated receptors, potentially useful compounds as anti-inflammatory drugs. Formulated peptide receptors (FPRs) belong to the family of G coupled receptors and so far three different human isoforms have been identified (FPR1, FPR2 / ALX and FPR3). Such receptors are expressed in most white blood cells and are therefore largely involved in the regulation of inflammatory processes. For this reason, they have been very interesting targets for new anti-inflammatory and immunomodulatory drugs. For this purpose they have been designed, synthesized and tested at the Department of Molecular Biology at Montana University, a large number of pyridazinone-based compounds that have been shown to act as agonists against FPRs with activity in the nanomolar range. In particular, selective agonists for FPR1, selective agonists for FPR2 and mixed agonists FPR1 / FPR2 were obtained. In addition, some of these compounds have been shown to stimulate chemotaxis at nanomolar concentrations. 4. Human neutrophils elastase inhibitors Recently, a new research topic has been addressed concerning human neutrophil elastase inhibitors, potentially useful compounds for the treatment of various inflammatory diseases such as COPD or cystic fibrosis. This project is also carried out in collaboration with the Department of Molecular Biology of the University of Montana. Within this work a new class of HNE inhibitors has been identified with N-benzoylindazole structure: the indazole scaffold has been shown to be adequate for HNE inhibitors: in fact, many compounds of this new series have activity values ​​in the nanomolar and a good selectivity against other proteases such as thrombin, chymotrypsin and the like urokinase. Finally, action mechanism studies have shown that our products act as pseudo-reversible competitive inhibitors.