Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes
Thesis (MSc)--Stellenbosch University, 2024.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Published: |
Stellenbosch : Stellenbosch University
2025
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867614085939462144 |
|---|---|
| access_status_str | Open Access |
| author | Van der Merwe, Leandre |
| author2 | Chellan, Prinessa |
| author_browse | Chellan, Prinessa Van der Merwe, Leandre |
| author_facet | Chellan, Prinessa Van der Merwe, Leandre |
| author_sort | Van der Merwe, Leandre |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description |
Thesis (MSc)--Stellenbosch University, 2024. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/131945 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:46:25.318Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/131945 Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes Van der Merwe, Leandre Chellan, Prinessa Kaschula, Catherine H Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science. Endoplasmic reticulum -- Pathophysiology Cancer -- Molecular aspects Organometallic compounds -- Therapeutic use Antineoplastic agents UCTD Thesis (MSc)--Stellenbosch University, 2024. ENGLISH ABSTRACT: Cancer continues to be a burden across the world, with breast cancer being the dominant cancer in women. Statistics released from the World Health Organisation each year reveal that, of the 10 million overall cancer deaths reported in 2020, 6.8% was due to breast cancer specifically. The well-known platinum-based drug, cisplatin, opened research into metallo-drug development specifically using ruthenium, rhodium and iridium. Inorganic drug discovery has, in recent years, shifted to using organometallic drug hybrids with known pharmacophores. Hybrids of breast cancer drugs, tamoxifen, 5-fluorouracil and paclitaxel linked to ferrocene and ruthenocene show good inhibitory effects against several cancer cell lines. Another pharmacophore studied is the antiplasmodial agent artesunate. Artesunate's mode of action is through the generation of reactive oxygen species, leading to endoplasmic reticulum stress and cell death. Dipyridyl ligands have shown good inhibitory activity against cancers linked to metal fragments. This project involves the synthesis and characterisation of novel organometallic complexes, containing dipyridyl-artesunate hybrids. The complexes were all obtained in moderate to good yields, with high purity. Characterisation done on these complexes include 1H and 13C NMR spectroscopy, FT-IR spectroscopy and electrospray ionisation mass spectrometry. The stability and solubility of these complexes were studied under physiological conditions to investigate how they could react once placed in an aqueous environment. The complexes were evaluated against two breast cancer cell lines, hormonal MCF-7 and onhormonal MDA-MB-231 and were found to have moderate to low activity against both cell lines. Complexes containing the artesunate moiety, TC1-TC3, showed higher activity compared to those without artesunate, LC1-LC3. LC1-LC3 showed low activity against the parasite Toxoplasma gondii and showed high cell viability. All complexes were relatively non-toxic against the normal breast cell line, MCF-12A and were selective for cancerous cells over normal cells. AFRIKAANSE OPSOMMING: Kanker bly 'n las regoor die wêreld, met borskanker wat die dominante kanker by vroue is. Statistieke, wat elke jaar van die Wêreldgesondheidsorganisasie vrygestel word, toon dat van die 10 miljoen algehele kankersterftes wat in 2020 aangemeld is, 6.8% spesifiek aan borskanker te wyte was. Die bekende platinum-gebaseerde middel, cisplatin, het navorsing geopen oor die ontwikkeling van metallo-geneesmiddels wat spesifiek rutenium, rodium en iridium gebruik. Die ontdekking van anorganiese geneesmiddels het in onlangse jare verskuif na die gebruik van organometaal-geneesmiddelsbasters met bekende farmakofore. Basters van borskankermiddels, tamoxifen, 5-fluorouracil en paclitaxel gekoppel aan ferroseen en rutenoseen toon goeie inhiberende effekte teen verskeie kankersellyne. Nog 'n farmakofoor wat bestudeer is, is die antiplasmodiale middel artesunaat. Artesunaat se werkingswyse is deur die generering van reaktiewe suurstofspesies, wat lei tot endoplasmiese retikulumstres en seldood. Dipiridielligande het goeie inhiberende aktiwiteit getoon teen kankers gekoppel aan metaalfragmente. Hierdie projek behels die sintese en karakterisering van nuwe organometaalkomplekse wat dipiridiel-artesunaatbasters bevat. Die komplekse is almal verkry in matige tot goeie opbrengste, met hoë suiwerheid. Karakterisering wat op hierdie komplekse gedoen word, sluit 1H en 13C KMRspektroskopie, FT-IR-spektroskopie en elektrosproei-ionisasie-massaspektrometrie in. Die stabiliteit en oplosbaarheid van hierdie komplekse is onder fisiologiese toestande bestudeer om te ondersoek hoe hulle kan reageer as dit in 'n waterige omgewing geplaas is. Die komplekse is geëvalueer teen twee borskankersellyne, hormonale MCF-7 en nie-hormonale MDA-MB-231 en daar is gevind dat dit matige tot lae aktiwiteit teen beide sellyne het. Komplekse wat die artesunaat-deel, TC1-TC3, bevat, het hoër aktiwiteit getoon in vergelyking met dié sonder artesunaat, LC1-LC3. LC1-LC3 het lae aktiwiteit teen die parasiet Toxoplasma gondii getoon en het hoë sellewensvatbaarheid getoon. Alle komplekse was relatief nie-giftig teen die normale borssellyn, MCF-12A en was selektief vir kankerselle bo normale selle. Masters 2025-04-30T10:04:02Z 2025-04-30T10:04:02Z 2024-12 Thesis https://scholar.sun.ac.za/handle/10019.1/131945 Stellenbosch University xxi, 156 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Endoplasmic reticulum -- Pathophysiology Cancer -- Molecular aspects Organometallic compounds -- Therapeutic use Antineoplastic agents UCTD Van der Merwe, Leandre Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| title | Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| title_full | Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| title_fullStr | Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| title_full_unstemmed | Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| title_short | Targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| title_sort | targeting the endoplasmic reticulum stress response in cancers with novel organometallic complexes |
| topic | Endoplasmic reticulum -- Pathophysiology Cancer -- Molecular aspects Organometallic compounds -- Therapeutic use Antineoplastic agents UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/131945 |
| work_keys_str_mv | AT vandermerweleandre targetingtheendoplasmicreticulumstressresponseincancerswithnovelorganometalliccomplexes |