Synthesis of proteasome inhibitors: analogues of nelfinavir

Dysko, Anna (2012) Synthesis of proteasome inhibitors: analogues of nelfinavir. Masters thesis, University of East Anglia.

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Nelfinavir 1 has been found to be a very successful nonpeptidic HIV-protease inhibitor.
According to a previous investigation, nelfinavir 1 proved to have an inhibitory effect on
chymotrypsin-like activity of 20S proteasome. Previous studies also show the
promotion of acceleration of the apoptosis process within cancer cells by inhibition of
proteasome activity. Separate experiments proved nelfinavir 1 to be involved in the
inhibition of Akt pathway – an enzymatic pathway that results in arrest of apoptosis and
prolongation of cell survival, which is also a very common mechanism in many types of
cancers. These characteristics made nelfinavir 1 a very promising target for the
anticancer therapy development. In this project, the synthesis of two nelfinavir 1
analogues was attempted, based on the replacement of the thiophenyl group by indole
or phenyl group to give 2 and 3 respectively.
The analogues were prepared in seven to eight steps from amino acids. Six of the
synthesised compounds have been tested biologically following the MTS colourimetric
assay procedure on THP-1 leukemia cells.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Users 2259 not found.
Date Deposited: 02 May 2013 11:02
Last Modified: 02 May 2013 11:02


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