Magister Scientiae - MSc (Pharmaceutical Chemistry)

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https://hdl.handle.net/10566/14970

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Browsing by Author "Joubert, Jacques"

Now showing 1 - 5 of 5
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    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.
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    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.
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    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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    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.
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    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.