Institute of Chemistry
Topic
Synthesis of potent and selective swainsonine-based inhibitors of Golgi α-mannosidase II
PhD. program
Organic chemistry
Year of admission
2025
Name of the supervisor
Ing. Maroš Bella, PhD.
Contact:
Receiving school
Faculty of Chemical and Food Technology, Slovak University of Technology
Annotation
Inhibition of Golgi α-mannosidase II (GMII) has a beneficial effect on cancer treatment, but co-inhibition of lysosomal α-mannosidase leads to severe side effects. Therefore, selective GMII inhibitors have been attracting attention as potential anticancer drugs for decades. Building on our previous results, the first goal of the doctoral project is to devise an improved synthesis of (5S)-5-benzylswainsonine, which was found to be a nanomolar and selective GMII inhibitor. The second aim of the research is to design and perform a synthesis of (5R)-5-benzylswainsonine to investigate the influence of the C-5 configuration on inhibitory activity and selectivity. The newly established synthetic protocols should allow for a rapid installation of a wide range of substituents into the C-5 position of swainsonine thus enabling a structure-activity relationship study.