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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

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    PhD Thesis (5.637Mb)
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    Publication date
    2020
    Author
    Abacha, Yabalu Z.
    Supervisor
    Falconer, Robert A.
    Shnyder, Steven D.
    Wright, Colin W.
    Keyword
    Medicinal plants
    Cytotoxic natural compounds
    Cancer
    Malaria
    Plasmodium falciparum
    Cryptolepine
    Vitellaria paradoxa
    Cyperus articulatus
    Securidaca longepedunculata
    Cryptolepis sanguinolenta
    Rights
    Creative Commons License
    The University of Bradford theses are licenced under a Creative Commons Licence.
    Institution
    University of Bradford
    Department
    School of Pharmacy and Medical Sciences, Faculty of Life Sciences
    Awarded
    2020
    
    Metadata
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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.
    URI
    http://hdl.handle.net/10454/19205
    Type
    Thesis
    Qualification name
    PhD
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    Theses

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