Escaping Bio-Assay Guided Isolation: Nature's Tools for Chemical Biology
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Quinn, Ronald J
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Grice, Irwin D
Liu, Miaomiao
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Abstract
World Health Organisation (WHO) announced in 2016 that TB is a top infectious disease killer worldwide with emerging multi drug resistance. Developing a new drug with different mechanisms is urgently needed. A successful outcome will significantly advance treatment of TB by identifying new and novel natural products that are biologically active against Mtb H37Rv and the recombinant mycobacterial lipoamide dehydrogenase (Lpd) enzyme. Identification of novel metabolites prior to commencing isolation will avoid re-isolation of known and inactive compounds and will save time and wasted effort in re-discovering the known. To achieve this, a previous high-throughput screening assay was developed and tested 202,983 natural product fractions sourced from a diverse collection of marine invertebrates, plants and fungi. A set of 574 Fractions were active against Mtb H37Rv and LPD enzyme. In this work, 94 dried ground biota samples (47 plants and 47 marine) were collected from Australia, Papua New Guinea and China. [...]
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Thesis (PhD Doctorate)
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Doctor of Philosophy (PhD)
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School of Environment and Sc
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The author owns the copyright in this thesis, unless stated otherwise.
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Subject
Mycobacterium tuberculosis
Mtb
Drug target
Native mass spectrometry
Tuberculosis