β-lactams from their structural features to their biological applications

Cirillo, Martina (2022) β-lactams from their structural features to their biological applications, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Chimica, 34 Ciclo.
Documenti full-text disponibili:
[img] Documento PDF (English) - Accesso riservato fino a 1 Maggio 2025 - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (6MB) | Contatta l'autore

Abstract

β-lactam compounds represent an important class of four-membered cyclic amides (azetidin-2-ones) thanks to their valuable and varied biological activities. The presence of a β-lactam ring in a series of bioactive molecules targeting different proteins, allows us to consider the azetidin-2-one a privileged structure. The constrained four-membered cyclic amide could easily undergo ring-opening reactions by nucleophilic residues in the active sites of enzymes and this is the mechanism suggested for antibacterial activity; moreover, the rigid core structure could favour and actually enhance directional noncovalent bonding for an effective ligand−receptor recognition. Nowadays monocyclic β-lactams are known as anticancer, antidiabetic, anti-tubercular, anti-inflammatory agents and as ligands of integrin receptors. In order to consider different facets of 4-azetidin-2-ones, this theis will be divided into two sections: the first one will be dedicated to the design, synthesis and characterization of biological active β-lactams (new β-lactam based integrin ligands and their different applications and novel N-thio-alkyl substituted azetidinones for the treatment of Tuberculosis); the second one instead, will be based on two projects which consider two different proprieties of β-lactams: stereochemistry, evaluated by biocatalytic methods and reactivity at C-4 position. In the first case we want to obtain enantiomerically pure 4-acetoxy-2-azetidinone, useful for synthesis of stereo-chemically defined bioactive β-lactams, while in the second case we want to study in which conditions the nucleophilic substitutions occur. A final section will be instead dedicated to the research project conducted in Philochem AG, Zurich, under the supervision of Prof. Dario Neri and Dr. Samuele Cazzamalli, based on the study of new cleavable disulfide linkers for small molecule drug conjugates targeting Fibroblast activation protein (FAP).

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Cirillo, Martina
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
34
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
β-lactams, integrins, drug-delivery systems, cytotoxic drug, anti-tubercular agents, biocatalysis, kinetic resolution, bio-materials, Sr-Hydroxyapatite, nucleophilic substitutions
URN:NBN
Data di discussione
20 Giugno 2022
URI

Altri metadati

Gestione del documento: Visualizza la tesi

^