Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension

Debele, Emmanuel Amoko (2013) Synthesis and evaluation of resveratrol-based nitroxides as potential treatments for hypertension. PhD thesis, Queensland University of Technology.


The synthesis and evaluation of novel resveratrol-based nitroxides have been explored for the potential treatment of hypertension. New methodology for the direct aryl iodination of isoindoline and isoindoline nitroxide using periodic acid and potassium iodide in concentrated sulphuric acid was developed. Diiodinated tetramethyl and tetraethyl isoindolines and a tetramethyl isoindoline nitroxide were prepared in excellent yields (70 – 82%). A diiodinated tetraethyl isoindoline nitroxide was generated from the corresponding nitroxide in modest yield (37%) alongside iodinated nitrones. The mono-iodinated species were also generated in modest yields (34 – 48%). Incorporation of the nitroxide unit into the structure of resveratrol was achieved using palladium-catalysed Heck coupling. Use of the previously prepared iodo products 5-iodo-1,1,3,3-tetramethylisoindolin-2-yloyl 18 and 5,6-diiodo-1,1,3,3-tetramethylisoindolin-2-yloyl 22 gave resveratrol nitroxides 12 and 13 in yields of 50% (optimized) and 1.6% respectively. Preliminary evaluation of the resveratrol analogue 12 as a treatment for hypertension was undertaken in the DOCA-salt rat model. A reduction in systolic blood pressure as well as alleviation of ventricular hypertrophy was observed. A larger study involving the DOCA salt rats is currently in progress.

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ID Code: 63990
Item Type: QUT Thesis (PhD)
Supervisor: Fairfull-Smith, Kathryn E. & Bottle, Steven
Keywords: Aryl iodination, cancer, cardiovascular diseases, DOCA-Salt, free radical, hypertension, iodination, neurodegenerative diseases, isoindoline, oxidative stress, reactive oxygen species, resveratrol, resveratrol-nitroxide, nitroxide
Divisions: Current > QUT Faculties and Divisions > Science & Engineering Faculty
Institution: Queensland University of Technology
Deposited On: 05 Nov 2013 04:14
Last Modified: 18 Jul 2017 14:45

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