{"id":{"repo_id":"east-anglia","oai_identifier":"oai:ueaeprints.uea.ac.uk:42344"},"canonical_url":"https://search.dev.ndltd.org/etd/east-anglia/oai:ueaeprints.uea.ac.uk:42344","repository":{"repo_id":"east-anglia","name":"University of East Anglia","base_url":"https://ueaeprints.uea.ac.uk/cgi/oai2"},"display":{"title":"Synthesis of proteasome inhibitors: analogues of nelfinavir","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.","abstract_html":"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_has_math":false,"creators":["Dysko, Anna"],"institution":"University of East Anglia","degree_name":"other","degree_level":"masters","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-05","date_published":"2012-05","updated_at":"2026-07-24T02:11:51Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Dysko, Anna"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-05"]},{"key":"dc:date.issued","label":"Date","values":["2012-05"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["School of Pharmacy"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of East Anglia"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://ueaeprints.uea.ac.uk/id/eprint/42344/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["masters"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["other"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://ueaeprints.uea.ac.uk/id/eprint/42344/1/2012DyskoAMSc.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Synthesis of proteasome inhibitors: analogues of nelfinavir"]}]}],"canonical_facts":{"dc:creator":["Dysko, Anna"],"dc:date":["2012-05"],"dc:date.issued":["2012-05"],"dc:description.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."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://ueaeprints.uea.ac.uk/id/eprint/42344/1/2012DyskoAMSc.pdf"],"dc:language":["en"],"dc:publisher.department":["School of Pharmacy"],"dc:publisher.institution":["University of East Anglia"],"dc:relation.isreferencedby":["https://ueaeprints.uea.ac.uk/id/eprint/42344/"],"dc:title":["Synthesis of proteasome inhibitors: analogues of nelfinavir"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["masters"],"dc:type.qualificationname":["other"]},"updated_at":"2026-07-24T02:11:51Z"}