- Title
- Antiproliferative activity of novel rhenium complexes and medicinal plant extracts
- Creator
- Oosthuizen, Kenneth Thomas
- Creator
- Venables, Luanne
- Subject
- Gqeberha (South Africa)
- Subject
- Eastern Cape (South Africa)
- Subject
- Medicinal plants -- South Africa
- Date Issued
- 2021-04
- Date
- 2021-04
- Type
- Master's theses
- Type
- text
- Identifier
- http://hdl.handle.net/10948/52028
- Identifier
- vital:43441
- Description
- Cancer is a complex, multifactorial disease that affects millions of individuals every year. The adverse side effects and escalating costs of current therapies coupled with the increased incidence of resistance to these therapies make it imperative that we explore novel treatments for the disease. This study investigated two avenues for novel drug design namely, novel synthetic compounds and medicinal plant extracts. The benzimidazole ring system has shown potential as a scaffold for designing novel anticancer agents. Conjugation of the metal rhenium to novel variants of this ring system open up the possibility of designing novel drugs that serve both a diagnostic and a therapeutic function. This study investigated the in vitro anticancer potential of ten such complexes against selected breast and cervical cancer cell lines. The selectivity of the complexes for cancer cells over normal cells was also investigated while the mechanism of action of effective complexes was determined by exploring cell cycle arrest, biochemical markers of apoptosis and mitochondrial membrane disruption. All ten complexes were screened against MCF7 breast and HeLa cervical cancer cell lines with four showing antiproliferative activity against both cancer cell lines and one showing cell line specific toxicity against MCF7 breast cancer cells. When looking at the SAR of the compounds it was noted that activity was higher in compounds which contain two potentially bidentate benzothiazole ligands, while compounds with potentially tridentate ligands show good activity, but only if the benzothiazole moiety is not involved in coordination. The complexes showed greater antiproliferative activity against the MCF7 breast cancer cells with IC50 values ranging from 3.2 to 7.0 µM versus a range of 7.6 to 24.4 µM being obtained on the HeLa cervical cancer cells. Antiproliferative complexes were tested against confluent and log phase Vero cells at their respective IC50 values to determine their effect on “normal” cells. Confluent Vero cells showed less cell death than those in log phase indicating that the complexes show preference for proliferating cells. The mechanism of action of the complexes was studied on both cancer cell lines via cell cycle analysis and apoptosis assays investigating phosphatidylserine translocation, caspase -3 and -8 activation and mitochondrial membrane potential with most complexes inducing cell cycle arrest followed by cell death via both the extrinsic and intrinsic pathways of apoptosis. Since 1940, 49% of all the available anticancer drugs approved for cancer treatment were natural products or directly derived from natural products. Plants are an excellent source of secondary metabolites, many of which are unique chemical compounds that cannot be synthesized in a laboratory. Ethnobotanical surveys conducted in conjunction with Traditional Health Practitioners of the Mkuranga and Same districts in Tanzania identified 25 plants that are used for the treatment of cancer. Four of these plants (A. mossambicensis, C. adenocaule, C. pseudopulchelusis and R. natalensis) with ethnobotanically reported anticancer usage showed cytotoxic activity against brine shrimp and were selected for further in vitro anticancer studies. All four plants were found to have antiproliferative activity against HeLa cervical cancer cells with IC50 values ranging from 3.4 to 50.8 µg/mL. This study was also tasked with investigating the mechanism of action of C. pseudopulchelus on HeLa cervical cancer cells by exploring cell cycle arrest, biochemical markers of apoptosis and mitochondrial membrane x disruption. C. pseudopulchelus caused early M phase arrest followed by slippage and subsequent cell death via the extrinsic pathway of apoptosis. In conclusion, this study showed that both novel complexes as well as medicinal plant extracts represent an interesting avenue for the development of novel anticancer drugs that are cheaper and produce less side effects than current therapies.
- Description
- Thesis (MSc) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (x, 140 pages)
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
- Rights
- All Rights Reserved
- Rights
- Open Access
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