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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-10112018-093244


Thesis type
Tesi di laurea magistrale LM5
Author
IACCARINO, RITA
URN
etd-10112018-093244
Thesis title
Synthesis of derivatives of fructose and its analogues for the development of molecular probes
Department
FARMACIA
Course of study
CHIMICA E TECNOLOGIA FARMACEUTICHE
Supervisors
relatore Prof.ssa Di Bussolo, Valeria
relatore Dott. Di Pietro, Sebastiano
Keywords
  • IR
  • GLUT5
  • cancer
  • metabolism
Graduation session start date
07/11/2018
Availability
Withheld
Release date
07/11/2088
Summary
Recent works suggest a strong convergence of opinions about the fact that a high amount of dietary fructose might play a significant role in cancer metabolism and may exacerbate the development of metabolic syndromes.
Hexoses uptake is involved in a wide range of human diseases, including diabetes, obesity, gout, cancer, sclerosis and Alzheimer’s.
There are two classes of hexose transporters: the active sodium coupled glucose transporters (SGLTs) and the passive glucose transporters (GLUTs1-14). In particular, the fructose cellular uptake seems to be largely mediated by the passive hexose transporters GLUT2 and GLUT5.
The epigenetic control of the Warburg effect and the abnormal expression of GLUTs in tumor cells represent a plausible target for the development of therapeutic agents and diagnostic imaging probes: in fact, glucose analogues such as 2-deoxy-2-(18F)fluoro-D-glucose (FDG) are already known as PET imaging agents. A valid alternative to this technique may be represented in certain cases by IR imaging, which might exploit a transparency window existing in cells and tissues between 2200 and 1800 cm-1.
Recently, fructose analogues and fructose uptake inhibitors possess an attracting interest due to its potential role in aggressive tumor growth and metabolic syndromes. In this perspective, we focused our attention on the synthesis of fructose derivatives in both furanosic and pyranosic forms. These target molecules were ultimately conjugated via copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) to an organic fragment bearing a portion containing IR probes, which display suitable absorption bands in the cellular transparency window.
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