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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-06222017-103224


Thesis type
Tesi di laurea magistrale LM5
Author
GIANNOTTI, MASSIMILIANO
URN
etd-06222017-103224
Thesis title
Synthesis of potential activators of GPR120
Department
FARMACIA
Course of study
CHIMICA E TECNOLOGIA FARMACEUTICHE
Supervisors
relatore Prof. Minutolo, Filippo
correlatore Dott.ssa Granchi, Carlotta
Keywords
  • Type two diabetes
  • GPR120 activators
  • GPR120
  • FFA4
Graduation session start date
10/07/2017
Availability
Withheld
Release date
10/07/2087
Summary
The GPR120 receptor belongs to the free fatty acid receptors (FFARs) family and consists in a G protein-coupled receptor. GPR120 is involved in the regulation of various metabolic processes, such as: control of inflammation (through inhibition of IKK-β/MKK4 pathways), increase of insulin secretion and decrease of glucagon secretion (mediated by the stimulation of the gastrointestinal hormone release), induction of glucose transporter 4 (GLUT4) translocation to cell membranes, appetite regulation, secretion of Ghrelin hormone, tumor promoting in human colorectal carcinoma (CRC) cells and a possible role in suppression of prostate cell-proliferation. It was seen that the dysfunction of GPR120 receptor is closely correlated with metabolic disorders, thus, it was taken into consideration as a novel potential therapeutic target for the treatment of obesity, insulin resistance and type 2 diabetes. Most of the compounds, synthesized up to now, have a carboxyl group inspired by the natural ligands, polyunsaturated fatty acids (PUFAs). However, the carboxyl acid moiety may lead to undesired effects. Furthermore, this functional group establish a strong ionic interaction, but it does not seem to be essential to maintain a high activity on GPR120. For these reasons, during my thesis period, I synthesized some new molecules as potential agonists of the GPR120 receptor based on the lack of the carboxyl acid moiety and other functional group.
All the synthesized compounds will be tested for to assess their activity on GPR120.
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