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Novel Anticancer Compounds From the Scilloideae Subfamily.

Langat, Linda Chepkirui. (2014) Novel Anticancer Compounds From the Scilloideae Subfamily. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

This study focused on the chemistry of Urginavia altissima (L.F) Speta, Ornithogalum dubium ‘Hybrid’ and Ornithogalum ponticum ‘Sochi’ of the Scilloideae subfamily (formerly Hyacinthaceae) of the Asparagaceae family. Plants belonging to the Scillodeae subfamily are widely used as medicinal plants in South Africa, Asia and Mediterranean regions for the treatment of various diseases including cancers. The compounds isolated previously from the species of the Scilloideae subfamily possess various biological activities including anticancer. In this study the bulbs of Urginavia altissima gave ten new bufadienolides (UA.1-UA.3, UA.5-UA.10 and UA.12), a known bufadienolide (UA.11), two known eudesmanes (UA.13, UA.14), a known 3-benzyl-4-chromanone type homoisoflavonoid (UA.15), a known polyhydroxylated compound, polybotrin (UA.16), a purine nucleoside, adenosine (UA.17) and a di-unsaturated hydroxylated fatty acid ethyl ester (UA.18). The bulbs of Ornithogalum dubium ‘Hybrid’ yielded three new (ODH.4-6) and three known (ODH.1-3) 3-benzyl-4-chromanone type homoisoflavonoids while the bulbs of Ornithogalum ponticum ‘Sochi’ gave three known cardenolide glycosides (OPS.1, 3, 5) with a rhamnose sugar attached at the C-3 position and oxidation occurring at the C-19 position. The structures of these compounds were determined using FTIR, MS, ID, 2D NMR studies and CD analysis. This study also investigated the anticancer activity and possible mode of actions of compounds isolated from Urginavia altissima by utilising the Computerised Pattern-recognition Algorithm (COMPARE) programme provided by the National Cancer Institute, USA, and molecular docking studies using Molecular Operating Environment (MOE 2012) software. The bufadienolides (UA.1-UA.10) were tested against the NCI 59 cancer cell lines. Compounds UA.1-UA.9 showed significant growth inhibition of cancer cell lines at five dose concentration level with good responses at the GI50, TGI and LC50 parameters. From COMPARE the bufadienolides correlated with standard agents that are DNA interacting, topoisomerase I and II inhibitors and DNA antimetabolites. Docking studies showed that bufadienolides (UA.1-5, 7-8, 12) interacted with B-DNA as groove binders and bufadienolides (UA.1-5, 7-8, 12) interacted with topoisomerase I and bufadienolides (UA.2-5, 8, 12) interacted with topoisomerase II. From the binding free energy results obtained from docking studies and the anticancer in vitro screen results, it can be concluded that the changes in the functionality of bufadienolides affect their anticancer activity and their binding affinities to DNA and topoisomerase I/II-DNA complexes.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Langat, Linda Chepkirui.
Date : 2014
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2014.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 12:07
Last Modified : 06 May 2020 12:13
URI: http://epubs.surrey.ac.uk/id/eprint/855740

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