Synthesis of proteasome inhibitors: analogues of nelfinavir
type: CreativeWork
description: 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.
abstract: 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.
author: Dysko, Anna
language: en
date published: 2012-05
date modified: 2026-07-24T02:11:51Z
provider: University of East Anglia
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of East Anglia