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The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents
Thesis (MSc)--Stellenbosch University, 2023.
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| Format: | Thesis |
| Language: | en_ZA en_ZA |
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Stellenbosch : Stellenbosch University
2023
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| _version_ | 1867613976821497856 |
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| access_status_str | Open Access |
| author | Ndlovu, Malcolm Thabo |
| author2 | Prinessa, Chellan |
| author_browse | Ndlovu, Malcolm Thabo Prinessa, Chellan |
| author_facet | Prinessa, Chellan Ndlovu, Malcolm Thabo |
| author_sort | Ndlovu, Malcolm Thabo |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2023. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/127070 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA en_ZA |
| last_indexed | 2026-06-10T12:44:42.460Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/127070 The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents Ndlovu, Malcolm Thabo Prinessa, Chellan Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science. Benzimidazoles Malaria -- Prevention Ferrocene Thesis (MSc)--Stellenbosch University, 2023. ENGLISH ABSTRACT: Malaria continues to be a major health concern despite efforts being made to curb the disease. This is evident from the latest world malaria report published by the World Health Organisation, pointing at a drastic increase in malaria cases and deaths in 2020 compared to 2019. This was attributed mainly to the disruption of malaria services as the world faced the COVID-19 pandemic, but there are also concerns over the continued increase in resistance of malaria towards currently available frontline treatments. Due to its various biological activities, the privileged benzimidazole scaffold has been explored in research based on the development of novel, effective antiplasmodial compounds, with overcoming malaria resistance in mind. The hybridisation of organic compounds with organometallic fragments in the search of highly effective biologically active compounds has become popular. The ferrocenyl moiety is one such organometallic fragment which has been explored, resulting in the potent antiplasmodial compound ferroquine, through hybridisation of chloroquine with ferrocene. In this study, a small library of four ferrocenyl benzimidazole compounds was successfully synthesised and obtained with high purity. The compounds were characterised by 1H NMR, 13C NMR and FTIR spectroscopy. The compounds were further analysed by mass spectrometry. Once synthesised, the stability and reactivity of the compounds under physiological conditions was investigated. To probe their possible mode of action the ferrocenyl benzimidazole derivatives were evaluated against Toxoplasma gondii, a model apicomplexan parasite. Two of the synthesised compounds (TC2 and TC3) were found to be moderately active. The active compounds were found to trigger the production of reactive oxygen species (ROS) within the parasite, making ROS production one of their modes of action. The antiplasmodial activity of the synthesised compounds was investigated against the chloroquine sensitive NF54 strain of Plasmodium falciparum, where one of the target compounds (TC1) was found to be moderately active. Evaluation for cytotoxicity against two human cell lines of healthy cells showed the synthesised compounds were relatively non-toxic. AFRIKAANS OPSOMMING: Malaria bly 'n groot gesondheidsprobleem ondanks pogings wat aangewend word om die siekte hok te slaan. Die jongste wêreldmalariaverslag wat deur die Wêreldgesondheidsorganisasie (WHO) gepubliseer is, wys op 'n drastiese toename in malariagevalle en sterftes in 2020 in vergelyking met 2019. Dit is hoofsaaklik toegeskryf aan die ontwrigting van malariadienste aangesien die wêreld die COVID-19 pandemie in die gesig gestaar het, maar daar is ook kommer oor die voortgesette toename in weerstand van malaria teen tans beskikbare behandelings. As gevolg van sy verskeie biologiese aktiwiteite, is die bensimidasool steier ondersoek, in navorsing gebaseer op die ontwikkeling van nuwe, effektiewe antiplasmodiale verbindings, met die oorkoming van malariaweerstand in gedagte. Die verbastering van organiese verbindings met organometaalfragmente in die soeke na hoogs effektiewe biologies aktiewe verbindings het gewild geword. Die ferrosenieldeel is een so 'n organometaalfragment wat ondersoek is, wat die kragtige antiplasmodiese verbinding ferrokien tot gevolg het, deur hibridisering van chlorokien met ferroseen. In hierdie studie is 'n klein biblioteek van vier ferrosenielbenzimidasoolverbindings suksesvol gesintetiseer en met hoë suiwerheid verkry. Die verbindings is gekenmerk deur 1H KMR, 13C KMR en FTIR spektroskopie. Die verbindings is verder deur massaspektrometrie ontleed. Sodra dit gesintetiseer is, is die stabiliteit en reaktiwiteit van die verbindings onder fisiologiese toestande ondersoek. Om hul moontlike werkingswyse te ondersoek, is die ferrosenielbenzimidasool derivate geëvalueer teen Toxoplasma gondii, 'n model apicomplexan parasiet. Daar is gevind dat twee van die gesintetiseerde verbindings (TC2 en TC3) aktief is. Daar is gevind dat die aktiewe verbindings die produksie van reaktiewe suurstofspesies (ROS) binne die parasiet veroorsaak, wat ROS-produksie een van hul maniere van werking maak. Die antiplasmodiese aktiwiteit van die gesintetiseerde verbindings is ondersoek teen die chlorokien-sensitiewe NF54-stam van Plasmodium falciparum, waar gevind is dat een van die teikenverbindings (TC1) baie aktief is. Evaluering vir sitotoksisiteit teen twee menslike sellyne van gesonde selle het getoon dat die gesintetiseerde verbindings relatief nie-toksies was nie. Masters 2023-03-01T09:49:03Z 2023-05-18T07:02:48Z 2023-03-01T09:49:03Z 2023-05-18T07:02:48Z 2023-03 Thesis http://hdl.handle.net/10019.1/127070 en_ZA en_ZA Stellenbosch University 147 pages : Illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Benzimidazoles Malaria -- Prevention Ferrocene Ndlovu, Malcolm Thabo The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents |
| title | The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents |
| title_full | The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents |
| title_fullStr | The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents |
| title_full_unstemmed | The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents |
| title_short | The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents |
| title_sort | synthesis and study of novel ferrocenyl benzimidazole derivatives as antiplasmodial agents |
| topic | Benzimidazoles Malaria -- Prevention Ferrocene |
| url | http://hdl.handle.net/10019.1/127070 |
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