Chemical and Biological Studies of Hibbertia Scandens (Snake Vine)
Access status:
USyd Access
Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Alreemi, RoaaAbstract
The First Australian Community is one of the ancient civilizations which depended upon the available surrounding natural resources for their clothing, nutrition and healing of disease. Unfortunately, some of their traditional medicines and / or their practical applications are lost ...
See moreThe First Australian Community is one of the ancient civilizations which depended upon the available surrounding natural resources for their clothing, nutrition and healing of disease. Unfortunately, some of their traditional medicines and / or their practical applications are lost because of poor written documentation. Plants form parts of ancient remedies used by Aboriginal and Torres Strait Islander peoples to heal ailments due to their antibacterial and antiviral activities. One of these medicinal plants is Hibbertia Scandens (Snake Vine), which was used in Aboriginal Communities’ traditional medicines to treat sores and rashes. In the current study, the leaves and roots of H. scandens were extracted using solvents ranging from less polar to more polar, and these extracts were chemically profiled by HPLC and LCMS. The bioactivity of these extracts was tested against the MCF-7 breast cancer cell line using the MTT assay; four extracts of the eight showed cytotoxic activity against MCF-7, with GI50 less than 100 μg/mL after 48 hours incubation. The DCM extract from the plant roots exhibited the greatest growth inhibition potential, with the lowest GI50 (45.7 μg/mL) after treatment for 48 hours. This extract was chosen for further studies and was further separated into twelve fractions using semi-preparative HPLC; the bioactive fractions were identified by an MTT cytotoxic analysis, with four fractions (8, 9, 10 and 12) showing an anti-proliferative effect. Fraction 8 was identified as β-sitosterol (14) and fraction 12 as β-sitosterol glucoside (18) using spectroscopic techniques. β-Sitosterol was chosen for further semi-synthetic studies as it is has known anticancer activity. Seven derivatives were produced, six of which are novel analogues and their characterization was performed using several spectroscopic techniques, including 2D NMR, FT-IR, LRMS and HRMS. The growth inhibition potential of all of these derivatives was tested against two breast cancer cell lines (MCF-7 and MDA-MB-231). β-Sitosterol and four of its derivatives showed cytotoxic effects against MCF-7, while the growth of the other cell line (MDA-MB-231) was only affected by one derivative. The tetrazole (25) analogue was the most active derivative, with increased growth inhibitory activity against both breast cancer cell lines over the corresponding carboxylic acid analogue (GI50 10.67 μM against MCF-7 and 16.27 μM against MDA-MB-231). This analogue arrests both breast cancer cell lines in the G2/M phase after 72h of treatment with GI50 and GI50 × 2 concentrations, suggesting that it acts upon mitotic division.
See less
See moreThe First Australian Community is one of the ancient civilizations which depended upon the available surrounding natural resources for their clothing, nutrition and healing of disease. Unfortunately, some of their traditional medicines and / or their practical applications are lost because of poor written documentation. Plants form parts of ancient remedies used by Aboriginal and Torres Strait Islander peoples to heal ailments due to their antibacterial and antiviral activities. One of these medicinal plants is Hibbertia Scandens (Snake Vine), which was used in Aboriginal Communities’ traditional medicines to treat sores and rashes. In the current study, the leaves and roots of H. scandens were extracted using solvents ranging from less polar to more polar, and these extracts were chemically profiled by HPLC and LCMS. The bioactivity of these extracts was tested against the MCF-7 breast cancer cell line using the MTT assay; four extracts of the eight showed cytotoxic activity against MCF-7, with GI50 less than 100 μg/mL after 48 hours incubation. The DCM extract from the plant roots exhibited the greatest growth inhibition potential, with the lowest GI50 (45.7 μg/mL) after treatment for 48 hours. This extract was chosen for further studies and was further separated into twelve fractions using semi-preparative HPLC; the bioactive fractions were identified by an MTT cytotoxic analysis, with four fractions (8, 9, 10 and 12) showing an anti-proliferative effect. Fraction 8 was identified as β-sitosterol (14) and fraction 12 as β-sitosterol glucoside (18) using spectroscopic techniques. β-Sitosterol was chosen for further semi-synthetic studies as it is has known anticancer activity. Seven derivatives were produced, six of which are novel analogues and their characterization was performed using several spectroscopic techniques, including 2D NMR, FT-IR, LRMS and HRMS. The growth inhibition potential of all of these derivatives was tested against two breast cancer cell lines (MCF-7 and MDA-MB-231). β-Sitosterol and four of its derivatives showed cytotoxic effects against MCF-7, while the growth of the other cell line (MDA-MB-231) was only affected by one derivative. The tetrazole (25) analogue was the most active derivative, with increased growth inhibitory activity against both breast cancer cell lines over the corresponding carboxylic acid analogue (GI50 10.67 μM against MCF-7 and 16.27 μM against MDA-MB-231). This analogue arrests both breast cancer cell lines in the G2/M phase after 72h of treatment with GI50 and GI50 × 2 concentrations, suggesting that it acts upon mitotic division.
See less
Date
2020Publisher
University of SydneyRights statement
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Faculty of Medicine and Health, Sydney Pharmacy SchoolAwarding institution
The University of SydneyShare