Roberts, NJ
(2016)
Old and new targets in antimalarial drug discovery.
PhD thesis, University of Liverpool.
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Abstract
The increasing emergence of resistance to commonly used therapies has placed a huge strain on the prevention and control of malaria; therefore, there is an urgent need to develop novel antimalarial agents. The aim of this research was to design and synthesise a library of potent antimalarial compounds, with desirable pharmacokinetic profiles, in order to identify a drug candidate suitable for preclinical development. This research was divided into two main sections: x The synthesis of compounds deigned to inhibit IspD, a novel target in antimalarial drug discovery x The late stage development of a series of endoperoxide-based antimalarials, which are derived from the structure of artemisinin A library of benzisothiazolinone compounds was generated to target the IspD enzyme. Many of these compounds displayed low micromolar inhibitory activity against both enzymatic and phenotypic assays in vitro and an investigation into structure-activity relationships around the core of these benzisothiazolinones was also conducted. The most potent compound to emerge, a CH2 linked benzisoselenazolone, had an IC50 of 0.17 μM against PfIspD and 5.54 μM against Pf3D7. These compounds represent a novel class of IspD inhibitor, ... (continues)
| Item Type: | Thesis (PhD) |
|---|---|
| Divisions: | Faculty of Science and Engineering > School of Physical Sciences > Chemistry |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Aug 2017 08:14 |
| Last Modified: | 27 Oct 2024 15:03 |
| DOI: | 10.17638/03007683 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3007683 |
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