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Fabrizia SORAGNI

Personale tecnico amministrativo presso: Dipartimento di Scienze della Vita sede ex-Scienze Farmaceutiche


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Pubblicazioni

2019 - Moretta di Vignola, da nicchia ad alimento funzionale [Articolo su rivista]
Bertelli, Davide; Marchetti, Lucia; Plessi, Maria; Soragni, Fabrizia; Bellelli, S.; Bergonzoni, L.; Dondini, L.; Grandi, M.; Venturi, S.; Etiopi, C.; Monari, W.; Bernardi, A.; Quartieri, G.; Lugli, S.
abstract

L'aricolo riporta i primi risultati del progetto di ricerca finanziato da Fondazione Vignola e Comune di vignola per la caratterizzazione chimica e funzionale e valorizzazione della Ciliegia "Moretta di Vignola"


2013 - Ligand-based discovery of N-(1,3-dioxo-1H,3H-benzo[de]isochromen-5-yl)-carboxamide and sulfonamide derivatives as thymidylate synthase A inhibitors [Articolo su rivista]
Ferrari S;Ingrami M;Soragni F;Wade RC;Costi MP
abstract

Phenolnaphthalein derivatives show potential for pharmacological activity as inhibitors of thymidylate synthase (TS) but difficulties in their synthesis and derivatization hinder their development. A deconstruction approach aimed at identifying a suitable new scaffold was proposed. A new scaffold was identified and two compound libraries based on this scaffold were designed. The carboxamide library (Library B) showed specific inhibition activity against Escherichia coli TS, whereas the sulfonamide library (Library C) showed a non-specific inhibition profile against hTS. N-(1,3-Dioxo-1H,3H-benzo[de]isochromen-5-yl)-sulfonamide derivatives, 1C and 9C, showed one order of magnitude improvement in inhibition constant against hTS with respect to the starting lead and represent potential compounds for further lead development.


2006 - Antibacterial agent discovery using thymidylate synthase biolibrary screening [Articolo su rivista]
Costi, Maria Paola; A., Gelain; D., Barlocco; S., Ghelli; Soragni, Fabrizia; F., Reniero; Rossi, Tiziana; Ruberto, Ippazio Antonio; C., Guillou; A., Cavazzuti; Casolari, Chiara; Ferrari, Stefania
abstract

Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H, 3H-naphtho[1,2-c]furan-1-one(5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC = 0.5-2.5 mu g/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.


2002 - Structure-based studies on species-specific inhibition of thymidylate synthase [Articolo su rivista]
Costi MP; Tondi D; Rinaldi M; Barlocco D; Pecorari P; Soragni F; Venturelli A; Stroud RM
abstract

Thymidylate synthase (TS) is a well-recognized target for anticancer chemotherapy. Due to its key role in the sole de novo pathway for thymidylate synthesis and, hence, DNA synthesis, it is an essential enzyme in all life forms. As such, it has been recently recognized as a valuable new target against infectious diseases. There is also a pressing need for new antimicrobial agents that are able to target strains that are drug resistant toward currently used drugs, In this context, species specificity is of crucial importance to distinguish between the invading microorganism and the human host, yet thymidylate synthase is among the most highly conserved enzymes. We combine structure-based drug design with rapid synthetic techniques and mutagenesis, in an iterative fashion, to develop novel antifolates that are not derived from the substrate and cofactor, and to understand the molecular basis for the observed species specificity. The role of structural and computational studies in the discovery of nomanalog antifolate inhibitors of bacterial TS, naphthalein and dansyl derivatives, and in the understanding of their biological activity profile, are discussed.


1999 - Thymidylate Synthase as a potential new target in drug resistance antimicrobial therapy. [Abstract in Atti di Convegno]
M. P. Costi; A. Gelain; I. Cardilicchio; F. Soragni; M. Rinaldi; P. Pecorari; D.Tondi; D.V. Santi
abstract

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