Bachelor with Honours Dissertations - open access

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https://hdl.handle.net/10292/14987
The "Bachelor with Honours Dissertations - open access" collection contains digital copies of AUT University B(Hons) dissertations approved for open access. B(Hons) dissertations are required to be open access from April 2022. Past students may contact the Tuwhera team (tuwhera.opentheses@aut.ac.nz) if they wish to make their B(Hons) open access.

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Browsing Bachelor with Honours Dissertations - open access by Supervisor "Fleming, Cassandra"

Now showing 1 - 3 of 3
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    Fluorescent Photolabile Caging Groups with Tuneable Sub-Cellular Localisation
    (Auckland University of Technology, 2022) Carmichael, Cailin Annie
    Photopharmacology is a rapidly emerging area of interest in the context of drug delivery. With the potential to dictate when and where a drug is active within a biological system, the combination of photopharmacology with targeted drug delivery could offer significant improvements for drug delivery by reducing toxicities and increasing bioavailability. Photocaging groups offer the ability to combine these two areas, with the photocage inhibiting the bioactivity of the drug until it is released, as well as providing a structure to which organelle-targeting ligands can be attached. This project aims to develop novel photocaging groups that also function as organelle-targeted drug delivery systems. Coumarin-derived photocages were selected for this project due to their fluorescent properties, non-toxic nature in biological systems, and ability to decage at wavelengths higher than 400 nm. To date, a novel coumarin-derived caging group containing a suitable synthetic handle to which organelle targeting ligands can be introduced has been developed.
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    The Design and Synthesis of Light Responsive GSK-3 Inhibitors
    (Auckland University of Technology, 2023) Clotworthy, Megan
    The inhibition of kinase enzymes has proven to be a valuable therapeutic approach for the treatment of various diseases (such as cancer, cellular metabolism and neurodegenerative disorders). Despite the large number of potent kinase inhibitors reported in the literature, many of these typically bind to multiple kinase targets and exhibit poor tissue selectivity, giving rise to undesired side effects. The idea of creating selective drugs has proven difficult, as once a drug is administered, there is very little control over when and where the drug is active within a biological system. The implementation of photopharmacology (the use of light to control the biological activity of a drug) into drug design and development could prove to be useful in developing molecular tools with improved tissue selectivity. Through the use of photocages, known drugs can be modified to be inactive. Only once administered to the cellular setting is the caged inhibitor exposed to a selected wavelength of light, liberating the active form of the drug at the desired target. This project focusses on the development of photocaged glycogen synthase kinase 3 (GSK-3) inhibitors through the introduction of fluorescent caging groups onto a key binding moiety. This project firstly entails the successful synthesis of a known GSK-3
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    The Design and Synthesis of Two-Photon Excitable Fluorescent Histone Deacetylase Inhibitors
    (Auckland University of Technology, 2022) Williamson, Jade
    This project focuses on the development of HDAC inhibitors that possess innate fluorescent properties. More specifically a potential fluorescent 6-amino-2,3-naphthalimide derived HDAC inhibitor has been synthesised, as a potential tool for cellular imaging studies. The abnormal regulation of HDAC activity has been linked to a number of diseases such as Alzheimer's, Parkinson’s, cancer, and many more. HDAC inhibitors are able to restore the regulation of these enzymes to help treat these problems. The synthesis of the target molecule included four main reactions; a nucleophilic acyl substitution to install the imide, followed by an amination at the 6-position of the naphthalimide ring, then hydrolysis of the tert-butyl ester, and finally an amide coupling to install the zinc binding group. NMR spectroscopy and mass spectrometry analysis supported that the target molecule has successfully been synthesised. Upon optimisation of the methodology needed to access such compounds, we attempted to synthesise three derivatives of the target compound by changing the amino group at the 6-position. The target compound 43 and the derivative compound 64 were also analysed for their HDAC activity, compound 43 showed incredibly good selectivity for class I HDACs 1 and 3, and compound 64 wasn’t as strong but still quite good results in terms of selectivity.
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