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Title: Synthesis of quinones with anticancer activity
Author: Visconti, Andrea
ISNI:       0000 0004 2737 1274
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Quinones attract the attention of chemists and biologists because of their unique structure and biological properties. Cancer is a leading cause of death worldwide, killing millions of people every year. Several antitumour agents, frequently employed in the treatment of different forms of cancer, contain in their structure the quinone motif, discovered to have marked cytotoxic effects. Chapter 1 presents an overview of the unique properties of quinones, with particular emphasis on their anticancer activity. Bioactivation of quinones by cellular reductive enzymes generates reactive oxygen species and/or alkylating species responsible for the cytotoxic effects of these compounds. Chapter 2 discusses the synthetic approaches to the novel quinone-containing natural product (+ )-terreusinone, recently isolated from the marine algicolous fungus Aspergillus terreus. Although the total synthesis of the natural product could not be accomplished, an innovative and efficient symmetric strategy, with a double Claisen rearrangement as the key step, led to the formation of the dipyrrolobenzoquinone core of ( + )-terreusinone. Chapter 3 describes the design, the synthesis and the biological evaluation of novel 2-unsubstituted indolequinones based on the structure of the indolequinones, previously synthesised in our group, that showed growth inhibitory activity against human pancreatic cancer cells in vitro and in vivo. Human thioredoxin reductase 1, a selenium-containing enzyme, was identified as the molecular target of these indolequinones. All the novel indolequinones made were tested for their anticancer activity in vitro against human pancreatic cancer and some of them were found very potent compounds at inducing inhibition of growth in human pancreatic cancer cells, confirming the potential use of these indolequinone-based compounds as a therapeutic approach to pancreatic cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available