Towards a treatment for stroke: a novel synthesis of dictyoquinazol A

Download files
Access & Terms of Use
open access
Copyright: Wangsahardja, Jonatan
Altmetric
Abstract
Stroke can be defined as a loss of brain function due to a disturbance of the blood flow. There are two types of stroke: ischemic and hemorrhagic stroke. Ischemic stroke is the most common type, but there is only one major treatment, called tissue plasminogen activator (tPA). This treatment is only effective in preventing paralysis if it is administered within 3–4 hours after the stroke symptoms occur. The paucity of other options highlights the need to develop a new treatment for ischemic and hemorrhagic stroke. Dictyoquinazol A is a mushroom-derived natural product which exhibits dose-dependent neuroprotective activity. The promising properties of dictyoquinazol A make it an attractive candidate for developing into a novel treatment for stroke. This project develops a new and improved total synthesis strategy for dictyoquinazol A, such that the natural product and its analogues can be synthesised easily. The key aspect in this novel synthesis strategy is to exploit the “hidden symmetry” of the target molecule. The target analogues gave chemical diversity both at the periphery of the molecule and in terms of modifications to the central quinazolinone moiety. Then, in vitro assays were deployed to measure the neuroprotective activity of dictyoquinazol A and analogues under conditions that mimic stroke attack, namely, excitotoxicity, oxidative stress. This work allowed the biological effects of dictyoquinazol A to be investigated more broadly than had been done in the past. It also allowed a preliminary structure-activity relationship study to be carried out, with some analogues even showing improved activity. This work has contributed to the overall effort to develop a novel treatment for stroke.
Persistent link to this record
Link to Publisher Version
Link to Open Access Version
Additional Link
Author(s)
Wangsahardja, Jonatan
Supervisor(s)
Hunter, Luke
Creator(s)
Editor(s)
Translator(s)
Curator(s)
Designer(s)
Arranger(s)
Composer(s)
Recordist(s)
Conference Proceedings Editor(s)
Other Contributor(s)
Corporate/Industry Contributor(s)
Publication Year
2015
Resource Type
Thesis
Degree Type
Masters Thesis
UNSW Faculty
Files
download public version.pdf 29.94 MB Adobe Portable Document Format
Related dataset(s)