This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonMany plants in biodiversity hotspots have not yet been screened for biological activity in humans. Plants synthesise secondary metabolites that may be unique to each species or induced in response to specific conditions. Assam in North East India forms part of the Indo-Burma biodiversity hotspot for conservation and is a rich source of medicinal plants for traditional Indian medicine. This study concerns the potential cytotoxic effects of three Assamese medicinal plant extracts, from Clitoria ternatea root, Mucuna pruriens seed and Cheilocostus speciosus rhizome. The aim of the study was to characterise the cytotoxic activity, to elucidate the biological mechanism and to isolate the bioactive agents for further investigation. Clitoria was prioritised for study, as its crude extract was found to have a dose related, cytotoxic effect that was 2-3 fold more effective on breast cancer cells than non-cancer cells. Two bioactive fractions of Clitoria were isolated in bioassay-led fractionation with high performance liquid chromatography. The fractions demonstrated a selective dose related cytotoxic effect over a range of 100 to 700 ng/μL. In live cell observation, crude extract and a bioactive fraction were cytostatic at non-lethal treatment doses, and crude extract reduced cells’ motility by 50%. Both crude extract and fractions caused structural changes in the actin cytoskeleton which could be contributing to the cytotoxic and cytostatic effects and reduced motility. Liquid Chromatography-Mass Spectrometry analysis indicates that the two isolated bioactive agents are novel homoisoflavones, polyphenolic secondary metabolites, which were also detected in extracts made from Indonesian sourced Clitoria root and are likely to be in extract made from UK sourced Clitoria root. Results suggest that bioactive components of Clitoria extract are worthy of further study and may provide lead compounds for new cytotoxic or antiproliferative anti-cancer therapies.Brunel University Londo
