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Title: Antibacterials from plants of the tropical rain forests of Borneo
Author: Teo, Stephen Ping
ISNI:       0000 0004 7964 9821
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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The tropical rain forests of Borneo are global hotspots for plant biodiversity which also harbour diverse chemical compounds and play an important role in folk medicine. Such phytochemicals have potential medicinal properties including as antibacterials. The search for new and novel antibacterials and resistance-modifying compounds is urgently required as the overuse or abuse of antibiotics has rendered many 'last line of defence' antibiotics ineffective. This study attempted to screen plant extracts from 5 selected plant families from Borneo for antibacterial activities. In addition to isolating and elucidating the structures of the compounds, bio-guided assay (broth dilution assay and agar dilution assay) were used to screen the plant extracts as well as the potency of the bioactive compounds isolated. Various chromatographic and spectroscopic techniques were employed to isolate the bioactive compounds from the extracts and to elucidate their structures respectively. Investigations were also undertaken to understand the mechanisms of action through various selected assays (accumulation, inhibition of biofim formation assay, and plate conjugation assays). This study led to the isolation of mainly phenolic compounds (e.g. xanthones, coumarins and styryllactones) but also some terpenoids (e.g. iridiod and diterpenes) and an alkaloid. They were either broad spectrum against different strains of both Gram-positive and Gram-negative and acid-fast bacilli or specific against one type of bacteria. Styryllactones and an alkyl benzoic acid isolated from Goniothalamus longistipetes exhibited broad-spectrum activities against Gram-positive, Gram-negative and acid-fast bacteria. Prenylated xanthones (STP10) isolated from Garcinia celebica gave the best activities against Gram-positive bacteria including the resistant strains with activities of between 1-4 µg/mL while STP10 also showed the best activities against Mycobacterium bovis BCG at 1.98 µg/mL This was followed by a diterpene (STP19) at 3.91 µg/mL while a styryllactone isomer (STP7), a pyranone (STP11) and a diterpene (STP18) all displayed an MIC of 7.81 µg/mL. Additionally, the diterpene (STP19) showed the best activities in inhibiting both bacterial efflux pumps and Inhibition of biofim assay. The alkyl benzoic acid (STP6) also inhibited the transfer of the bacterial plasmid pKM101 in plate conjugation assay with a 70% reduction. One of the styryllactones (STP8) screened exhibited the best activities against liver cancer (Hep G2) cell lines with IC50 at 0.986 µg/mL All the bioactive compounds followed the Lipinski's rule of 5 for druglikeness.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available