Name: Lucrezia Margherita Comparini
Phone: 050 221 9692
Supervisors: Mauro Pineschi
Ph.D. project Title: Development of new small molecules targeting GLP-1 secretion.
Research summary: 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.
ORCID identifier: 0000-0002-2259-3260