Biocatalytic synthesis of novel oxidized aromatic compounds as potential anti-bacterial and anti-cancer agents
Date
2016-01-19
Authors
Ogunleye, Tozama
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Abstract
According to the World Health Organization (WHO), cancer is a leading cause of death
worldwide and has accounted for 7.6 million deaths (13% of all deaths) in 2008. The number
of effective drugs available has been reduced by chemo resistant malignant tumors. Similarly,
bacterial infections are one of the world’s most pressing public health problem. The major
challenge in anti-bacterial treatment is due to the development of bacteria strains that are
resistant to antibiotics. Each year more than 11 million people die from major infections such
as MDR tuberculosis. In 2013, 9 million people fell ill with TB and 1.5 million died from the
disease (WHO). Therefore there is a need for novel therapeutic alternatives such as the
discovery of new anti-cancer and anti-bacterial agents. Benzofurans have attracted much
attention due to their broad spectrum of pharmacological activities such as anti-cancer and
anti-bacterial activities and one classical example is usnic acid. Most of the published
synthesis of the benzofuran moiety involved the formation of annellated furan ring by
intramolecular cyclisation of benzene, and these procedures involved a multi-step, rigorous
reaction conditions and expensive catalyst. This research investigated the novel synthesis of
benzofurans through the application of biocatalysis, where the reactions involved the use of
the oxidative enzyme laccase to generate carbon-carbon bonds, carbon-oxygen and carbonnitrogen
bonds between aromatic compounds. The substrates used were o-diols from
catechols 1, p-quinone 2 from naphthoquinones and naphthohydroquinone 3, which, when
activated by the enzyme action, could be reacted with 1,3-diketones 4, 5 or coumarins 6
(Figure 1). The aim of synthesising different classes of compounds was to vary the functional
groups and to increase the number of rings, so as to possibly increase the biological activities.
Description
A dissertation submitted
In fulfilment of the degree
Doctor of Philosophy
(Chemistry)
In the
Faculty of Science
School of Chemistry
University of the Witwatersrand. Johannesburg 2015.