Magister Scientiae - MSc (Pharmaceutical Chemistry)

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Medication administration by nasogastric tube
(Universty of the Western Cape, 2024) Van Antwerpen, Monet; McCartney, Jane
Nasogastric tubes (NGTs) are commonly used in hospital settings for administering medicine to patients who, for various underlying reasons, experience dysphagia. Nurses are the healthcare providers primarily responsible for medicine administration while pharmacists must ensure the safe and rational use of medicines and medicine administration. There are many practical challenges associated with nasogastric medicine administration, and guidelines on medicine administration via this route are suggested to minimise these challenges. These challenges, although encountered daily in the hospital setting, do not appear to have been described in a South African context. In addition, there seems to be a lack of guidelines and information available for prescribers or nurses to prevent or minimise these medicine administration problems from occurring.
Discovery of heat shock protein90 inhibitors using structured-based virtual screening
(University of the Western Cape, 2023) Ngcagawule, Siyasanga; Joubert, Jacques
Alzheimer's disease (AD) is the most common irreversible dementia, caused by accumulation of protein aggregates in the central nervous system, with symptoms that include memory loss and behavioural abnormalities. Cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartate receptor (NMDAR) antagonists are current treatment options for mild to moderate AD. These agents are not used to cure the illness, but rather as symptomatic therapy. Heat Shock Protein (HSP90), is one of the molecular chaperones that plays a role in AD pathogenesis. HSP90’s main function is to regulate the heat shock factor-1 (HSF-1) transcription factor, which is the key regulator of the heat shock response. Inhibition of HSP90 activates HSF-1 and the subsequent induction of heat shock proteins such as HSP70, HSP40 and HSP27. Such protein assist the folding of newly synthesized or misfolded proteins, preventing their aggregation. Therefore, HSP90 inhibitors protect against protein toxicity and reduces brain aggregate to form in AD. The HSP90 protein crystal structure (PDB ID; 2bz5) was used to dock a diverse structural database of about 12 000 amine containing compounds from the Maybridge Screening Collection using Fast Rigid Exhaustive Docking (FRED). The top five hundred-docked compounds were viewed using Visualization & Communication of Modeling Results (VIDA), and the top 50 compounds were analysed for important binding interactions and low Chemgausse4 scores. Ten of these compounds were selected based on their interaction profile with the desired HSP90 active site amino acids. Thereafter, the ten MayBridge compounds were drawn on Sigma-Aldrich and searched for structures that show at least 70% similarity, to the selected MayBridge compounds.
The implementation of the African union model law on medical products regulation and the establishment of the African medicines agency
(University of the Western Cape, 2022) Ncube, Bakani Mark; Ward, Kim
Within Africa, there is insufficient access to quality, safe, efficacious and affordable medical products which can partly be attributed to lack of robust regulatory systems, a lack of competent regulatory professionals in national medicines regulatory authorities (NMRAs) and ineffective regional collaborations among NMRAs. In response to national regulatory challenges, a number of regional harmonisation efforts were introduced through the African Medicines Regulatory Harmonisation (AMRH) initiative to, among others, expedite market authorisation of medical products and to facilitate the alignment of national legislative frameworks with the African Union (AU) Model Law on Medical Products Regulation.
Assessing the influence of electronic media on student perceptions towards antibiotic resistance
(University of the Western Cape, 2022) Munyayi, Prudence Vimbai; Bheekie, Angeni
Antimicrobial resistance (AMR) and the reduced number of new antibiotic discoveries impose a major threat to the quality of human life and effective treatment options. Antibiotic resistant infections require prolonged hospital stays and treatment periods, that depend on more expensive regimens. The lack of knowledge and negative attitude among the public about antibiotics and antibiotic resistance has led to inappropriate antibiotic use.
A comparison between estimated renal function from point-of care derived cystatin c measurements and serum creatinine derived measurements
(University of the Western Cape, 2022) Mogakane, Khomotso Lesedi; Upton, Edward
Serum Creatinine (SCr) is the most commonly used and cost effective biomarker used to quantify estimated glomerular filtration rate. However, creatinine is affected by anthropometric parameters such as muscle mass, age and gender. Cystatin-C (CysC) is a low molecular weight protein which is freely filtered through the glomerulus. It has been said to be as accurate as plasma creatinine and is independent of limitations derived from anthropometric parameters. CysC can also be determined through point of care devices which do not require the phlebotomy or experienced laboratory personnel for its use. There have also been correlations noted in CysC serum concentrations and cardiovascular risk assessment.
Synthesis and characterisation of biomimetic immunostimulatory lipid-polymer hybrid nanoparticles
(University of the Western Cape, 2022) Irabin, Aime Fabius; Dube, Admire
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), remains a fatal infectious disease and one of the top ten leading causes of mortality, particularly in developing countries. Current drug therapy for TB is challenged by the poor physiochemical properties of the antibiotics used. These properties impact their bioavailability, toxicity, and treatment duration, thereby negatively impacting patient adherence. These factors also contribute to the emergence of the difficult to treat multi-drug resistant strains of M. tuberculosis. Recently, immunotherapy has emerged as a promising alternative treatment modality for TB.
Homology modelling and characterization of three-dimensional (3d) protein structures of selected variants of cyp3a4
(University of the Western Cape, 2022) Omotoso, Christianah Taye; Egieyeh, Samuel
The efficacy and toxicity of several drugs and prodrugs are influenced by the interindividual genetic variations in drug-metabolising enzymes. Cytochrome P450 enzymes constitute the major metabolising enzymes in humans. Cytochrome 3A4 (CYP3A4) is the highest abundantly expressed human cytochrome P450 enzyme metabolising about 40% of marketed drugs. Several studies have shown the significant effects of CYP3A4 single nucleotide variability on its enzymatic activity and the pharmacokinetic parameters of metabolized drugs. However, there is a paucity of information on the molecular characteristics (including threedimensional protein structures, physicochemical properties, and molecular dynamics characteristics) of single nucleotide variants of CYP3A4 enzymes that may be correlated with the reported variability of their enzymatic activities.
Investigating the Perception of the Influence of Pharmaceutical Marketing on Pharmacists and Doctors Dispensing and Prescribing Practices.
(University of the Western Cape, 2021) Tichiwangana, Nothando Yollanda; Obikeze, Kenechuku
Pharmaceutical marketing via a wide range of promotional tools to doctors and pharmacists is one of the primary methods used by the pharmaceutical industry to drive product sales. Pharmaceutical representatives are the key personnel employed in promoting pharmaceutical products, and their interactions with doctors and pharmacists may present a conflict of interest which may result in irrational prescribing or dispensing with the attendant negative outcomes for patients. As such, an awareness of the influence pharmaceutical marketing may have on their prescribing or dispensing practice is essential to mitigate its negative impact on professional practice. Although several studies have investigated the perception of healthcare professionals on the influence pharmaceutical marketing has on their prescribing and dispensing behaviour, no study has evaluated this in healthcare professionals in South Africa. This study aimed to investigate the perceptions and attitudes of doctors and pharmacists in private sector practice in Gauteng province of South Africa on the influence of marketing by pharmaceutical representatives on their decisions when prescribing and dispensing medication to patients. The study involved a mixed methods approach, using a semi-structured questionnaire to elicit information on doctors and pharmacists’ perceptions on gifts offered by pharmaceutical representatives, and the influence of pharmaceutical marketing on their dispensing and prescribing practice. A sample consisting of 120 doctors and pharmacists practising in the private sector of Gauteng province and who interacted with pharmaceutical representatives as part of their practice were included in the study using convenience sampling. The responses to the questionnaire were collated using descriptive statistics, and data analysed to identify relationships between the respondent’s perceptions and specific prescribing and dispensing practices using SPSS statistical software. The Chi-squared test was used to test for the differences between groups, and the Spearman rho coefficient used to analyse associations between identified themes in the data in SPSS. Ethical approval for the study was obtained from the University of Western Cape
Biosimilar’s Growth in Pharmerging Markets: An Analysis of the Regulatory Environments
(University of the Western Cape, 2020) Batel, Ryma; Samsodien, Halima
The introduction of biosimilars to health care markets across the globe has had some success in increasing competition and improving the cost of healthcare. While savings are important for driving the biosimilar uptake, this is not the only consideration for the growth of biosimilars onto emerging markets. A systematic review of the literature to assess the growth of biosimilars onto the emerging market was conducted using the following data sources: PubMed, Website of the Generics and Biosimilars Initiative (GaBI) journal, ProQuest, Google Scholar. Studies that provided evidence of biosimilars onto the emerging market through surveys and other sources of existing data were included. The systematic review process followed Wichor et al. (2018) and the PRISMA checklist (PRISMA, 2009). The search strategy for the review provided a total of 71studies, which underwent title, abstract and full text review to give 20 articles that fit the inclusion criteria for the aimed study. A quality assessment was conducted on the 20 articles and by using the Hawker et al. (2002) quality tool and directed research questions to set variables, the data analysis of 13 articles emerged. The included studies agreed on the growth of biosimilars onto the emerging market and on the switch to biosimilars to improve access to therapies. However, International Nonproprietary Name (INN) and physician confidence were still considered as hurdles. The two most successful drivers of the growth of biosimilars onto the emerging market based on this review was certainly the regulation of the process followed by the cost of biosimilars. To conclude, data analysis of 13 articles determined that the general perception of using biosimilars in emerging markets is positive. However, for successful integration into routine healthcare and uptake into these markets, there must be a direct focus on the regulation of Biosimilars
Chalcone and curcumin hybrids of indole propargylamines as multifunctional neuroprotective agents
(University of the Western Cape, 2020) Musakwa, Lovetone; Joubert, Jacques; Malan, Sarel
Neurodegenerative disorders (NDs) are a range of chronic brain disorders that includes amongst others motor function loss. Parkinson’s disease (PD) is one of the common NDs that has an insidious onset and diagnosed when dopaminergic neurons in the substantia nigra are already lost. The loss creates a deficiency of the dopamine (neurotransmitter) thereby causing neurochemical imbalance resulting in the signs and symptoms of PD. NDs overlap at multiple levels so some of the symptoms overlap as well. NDs currently have no cure yet and current drug therapies only improve the quality of life of the patients by targeting the symptoms mainly. Treatment of PD currently involves different classes of drugs and depending on the stages of the disease, some drugs can be only used as an adjunct therapy. Anti-oxidants and monoamine oxidase inhibitors (MAO-I) are part of the treatment options.
Selection, synthesis and evaluation of novel drug-like compounds from a library of virtual compounds designed from natural products with antiplasmodial activities
(University of the Western Cape, 2020) Pokomi, Rostand Fankam; Joubert, Jacques; Malan, Sarel; Egieyeh, Samuel
Malaria is an infectious disease which continues to kill more than one million people every year and the African continent accounts for most of the malaria death worldwide. New classes of medicine to combat malaria are urgently needed due to the surge in resistance of the Plasmodium falciparum (the parasite that causes malaria in humans) to existing antimalarial drugs. One approach to circumvent the problem of P. falciparum resistance to antimalarial drugs could be the discovery of novel compounds with unique scaffolds and possibly new mechanisms of action. Natural products (NP) provide a wide diversity of compounds with unique scaffolds, as such, a library of virtual compounds (VC) designed from natural products with antiplasmodial activities (NAA) can be a worthy starting point.
Synthesis and evaluation of 7-substituted 3-propargylamine coumarin derivatives as multifunctional monoamine oxidase and cholinesterase inhibitors for Alzheimer’s Disease treatme
(University of Western Cape, 2020) Mzezewa, Sheunopa C.; Joubert, Jacques; Malan, Sarel
Alzheimer’s Disease (AD) is a neurodegenerative disease which results from the irreversible loss of neurons in the brain. The disease is characterized by progressive cognitive impairment with recurrent short-term memory loss. AD is the leading cause of dementia and 4th leading cause of death in the elderly. Success in the treatment of AD has been limited, with drugs only treating it at a symptomatic level due to its pathology being complex and poorly understood. However, it is known that the cholinesterase and MAO-B enzymes play an important role in the disease through their association with production of amyloid plaques and oxidative stress respectively, two mechanisms associated with cell death and the symptoms seen in AD.
Discovery of anti-mycobacterial natural products from South African marine algae
(University of the Western Cape, 2019) Mukaddam, Zaahirah; Beukes, Denzil
Tuberculosis is a communicable disease which affects millions of people around the world. Although the case reports are declining, the eradication rate of this disease is far too slow. Natural products have played a key role in the treatment of the disease. However, tuberculosis is developing resistance to current first-line therapy. In this study, a prefractionated marine algal library was developed in order to identify and prioritise samples for isolation of their active metabolites which exhibit anti-tuberculosis activity. Based on the results of the library screening and chemical profiling, two seaweeds were selected for further investigation, Laurencia glomerata and Plocamium cornutum. The extraction and fractionation of Laurencia glomerata and Plocamium cornutum resulted in the isolation of three chamigrane seqsuiterpenes (prepacifenol epoxide, johnstonol and one newly proposed structure) and two monoterpenes (cartilagineal and 1,5,6-trichloro-2-(dichloromethyl)-6-methylocta-1,3,7-triene) respectively. The structures of these compounds were elucidated by 1 and 2D NMR data and were confirmed by literature comparisons. Although some of the initial library factions screened showed rather good activity against Mycobacterium tuberculosis, the selected seaweed fractions showed greater activity against M. aurum. The isolated monoterpenes showed moderate cytotoxicity against the cancer cell line MCF-12a and the sesquiterpenes however were more selective for MCF-7. The monoterpenes showed both activity and potential selectivity towards Mycobacterium tuberculosis.
Active encapsulation of diclofenac sodium into liposomes for ophthalmic preparations
(University of the Western Cape, 2018) Alonjang, Evelyne Nguelweh; Ebrahim, Naushaad
Liposomes as a drug carrier in the pharmaceutical industry has gained currency since its discovery in 1965 by Bangham A. D. Liposomes have been shown to improve bioavailability as they can be delivered to target sites and possess sustained release properties which could be used to mitigate certain weaknesses associated with current diclofenac sodium eye drops. Diclofenac sodium (DNa) eye drop is a sterile Nonsteroidal Anti-inflammatory Drug (NSAID) with diclofenac sodium as its active ingredient. It is indicated for the lessening of ocular pain, prevention of miosis in eye operations, easing of postoperative inflammation and cystoids macular edema. The residence time of eye drops after application has been found to be 1-2 minutes as a result of continuous production of tears diluting the active ingredient, draining the eye drops into the nasolacrimal path, and eliminating it during blinking. As a result of the active ingredient not residing at the target site for the required duration, more frequent administration and medication is required and the risk of non-compliance is increased. Given the aforementioned potential of liposomes to redress the above weaknesses of current eye drops (dosage form) available for diclofenac sodium ophthalmic application, this study sought to encapsulate diclofenac sodium into liposomes for ophthalmic application. The main components of liposomes (cholesterol and phosphotidylcholine) and incubation time were set as the independent variables while percentage encapsulation, polydispersity index (PDI) and drug release profile constituted the dependent variable. Using analysis of variance (ANOVA) and t-test statistics, the interaction between the independent variables and their effect on the dependent variables were tested.
Post-market assessment of the quality of first line regimen fixed-dose combination antiretrovirals in South Africa
(University of the Western Cape, 2017) Suleiman, Reem Abdallah S.; Ward, Kim; Dube, Admire
The rapid increase in access to new antiretrovirals (ARVs) worldwide and, especially in sub-Saharan Africa, coupled with the well-documented problem of poor quality ARVs in developing countries has underscored the need for quality assessment of these medicines. South Africa has the worst human immunodeficiency virus (HIV) epidemic profile in the world; consequently, it has rolled out the world's largest antiretroviral ARV programme. With increasing market penetration of generic medicine in South Africa and especially ARVs, there is a call for stringent quality control mechanisms following the marketing approval (post-market quality control) of these medications. Unfortunately, evidence suggests that the World Health Organisation (WHO) recommendations for this aspect of quality assurance is not met by most Medicine Regulatory Authorities. In South Africa and many other countries this is attributed to a lack of physical and financial resources to enforce effective post-marketing surveillance (PMS) of all pharmaceuticals available in the country.
Evaluation of the effect of polyethylene glycol incorporation on the performance of poly(lactic-co-glycolic acid) nanoparticles
(University of the Western Cape, 2016) Samkange, Tendai; Dube, Admire
Nanoparticle drug delivery is challenged by the binding of proteins in blood which result in their rapid removal from the circulatory system. Nanoparticles engineered to delay protein binding have shown to have extended circulatory times. One such engineering technique is PEGylation, which is the coating of nanoparticles with polyethylene glycol (PEG). PEG shields the nanoparticle from adhesive interactions with proteins. However, the optimal PEG content required to impart this "stealth" property onto poly(lactic-co-glycolic acid) (PLGA) nanoparticles, is unknown. Moreover, the effect of PEGylation on drug release has not been thoroughly investigated.
Novel adamantane-chloroquinolin conjugates to overcome plasmodium falciparum chloroquine resistance
(University of the Western Cape, 2017) Yvette, Mofenge Opute; Joubert, Jacques; Malan, Sarel
Malaria poses devastating health and socioeconomic outcomes on global health especially among pregnant women and children below the age of 5 in endemic areas. This is exacerbated by Plasmodium falciparum resistance to available antimalarial drugs, especially chloroquine (CQ), which was the drug of choice for many years against the blood stage of malaria.

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