Natural product isolation and derivatisation towards leukaemia therapeutics

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Li, Xingjian (2019). Natural product isolation and derivatisation towards leukaemia therapeutics. University of Birmingham. Ph.D.

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Abstract

Natural product, Parthenolide (PTL), is one active component extracted from Feverfew (Tanacetum parthenium). Recent studies have shown that PTL can disrupt the redox homeostasis by depleting glutathione (abundant cellular antioxidant) or other intracellular thiol groups, causing a decrease in the levels of antioxidant; thereby exposing the cell to oxidative damage from endogenous reactive oxygen species (ROS). This property has been investigated for its potential to specifically target cancer cells which tend to have a higher basal level of ROS than normal cells. The poor aqueous solubility and non-selective reactivity of PTL are two major issues that limit its clinical study as a potential drug. As there is no treatment for chronic lymphocytic leukaemia (CLL) that works for all patients, the potential for the use of parthenolide derivatives in the treatment of this complex disease is being investigated. Therefore, we aim to solve these issues with parthenolide derivatives. To test our hypothesis, we chose to design and synthesise novel parthenolide derivatives as anticancer prodrugs. In addition, parthenolide was extracted, isolated and purified from a few different types of medicinal herb Feverfew grown on campus (Winterbourne Botanic Garden) by procedures developed in this work.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):