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Investigation of Nigerian Ethno-medicinal Plants as Potential Sources of Cytotoxic and Anti-plasmodial Compounds. Biological activity of Vitellaria paradoxa, Cyperus articulatus, Securidaca longepedunculata and semi-synthetic halogenated analogues of cryptolepine isolated from Cryptolepis sanguinolenta
Abacha, Yabalu Z.
Abacha, Yabalu Z.
Publication Date
2020
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The University of Bradford theses are licenced under a Creative Commons Licence.
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Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy and Medical Sciences, Faculty of Life Sciences
Awarded
2020
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Abstract
Natural products are acknowledged sources of novel compounds for use in
the treatment of diseases such as cancer, malaria, and human African
trypanosomiasis. However, health burdens of such diseases still remain high,
with drug resistance leading to failure of current medication. Therefore, there
is a need for new treatments, and this project considers the potential of
Nigerian ethno-medicinal plants and their products. Firstly, the aims were to
isolate cytotoxic compounds through bio-guided evaluation and fractionation
from 3 medicinal plants; Vitellaria paradoxa, Cyperus articulatus and
Securidaca longepedunculata used traditionally in the treatment of cancer in
North-East Nigeria. Extracts from S. longepedunculata were the most active
when assessed in a panel of cancer cell lines, with IC50 values below 10 µg/ml,
whilst fractions isolated from V. paradoxa and C. articulatus were moderately
cytotoxic and able to overcome drug resistance mechanisms in drug resistant cell lines. In the second part of the thesis, novel cryptolepine analogues were
semi-synthesized using environmentally friendly methods and evaluated for
cytotoxic, anti-plasmodial and anti-trypanosomal activity. The compounds
were found to be highly cytotoxic in cancer cell lines with the ability to
overcome drug resistant mechanisms, with sub-µM IC50 values, and were also
active against drug resistant strains of Plasmodium parasites in addition to
Trypanosoma brucei, with IC50 values below 500 nM, and 300 pM respectively.
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Type
Thesis
Qualification name
PhD