Comparini Lucrezia Margherita

Contacts:

lucrezia.comparini@phd.unipi.it

Supervisor(s):

Professor Mauro Pineschi

PhD project Title:

Development of new small molecules targeting GLP-1 secretion

Abstract of the PhD project:

GLP-1 is an incretin hormone released by intestinal L-cells mostly after food ingestion. Binding its receptor, GLP-1 enhances the secretion of insulin from pancreatic b-cells, reduces gastric emptying and food intake. This makes GLP-1 receptor an interesting target for diabetes treatment, moreover, GLP-1 agonists have been proven to be neuroprotective and neuro-regenerative agents. GLP-1 mimetic peptides are commercially available, but they present problems such as low stability and compliance, and various side effects. 1,3-diaza-4-oxa-[3,3,1]bicyclic scaffolds obtained in our lab with a four-step linear synthesis, being small molecules with the right physicochemical feature for an oral administration, are effective candidates to enhance GLP-1 secretion both in vitro and in vivo. The aim of this research project is the construction of a library of compounds having this scaffold, the evaluation of their antidiabetic and neuroprotective activity, and the study of the mechanism of action.

Publications link:

Oral communications at conferences:

• “Development of antidiabetic small molecules acting as GLP-1 secretagogues” MYCS: Merk young chemist’ symposium, Rimini (Italy); 22-24/11/2021.
• “Chemical manipulation of biologically active heterobicycles” SCI- VISYOChem 2022, online, 24-27/10/2022.
• “Harnessing heterobicyclic reactivity to access chemical diversity” CINMPIS days, Pisa (Italy); 09-11/02/2023.
• “Development of ring-opening reactions of cyclic gem-diamines with Grignard reagents” “Attilio Corbella” International Summer School on Organic Synthesis (ISOS2023), Gargnano Italy); 18-22/06/2023.
• “Asymmetric synthesis of (-)-Quinagolide via enzymatic resolution and stereoselective iminium ion reduction” XLI Convegno Nazionale della Divisione di Chimica Organica della Società Chimica Italiana, Roma (Italy); 10-14/09/2023.