This project is focused on the synthesis and biological activity of aloin and derivatives. Aloin
is a C-glucoside anthrone that is found in Aloe marlothii, a common Southern African plant
used in traditional medicine. Aloin was isolated from A. marlothii, employing a selective
chelation isolation procedure. This compound is known to have numerous biologically active
properties, and can be used as a laxative, an anti-bacterial agent, an anti-oxidant, and as a
cytotoxic drug against breast and ovarian tumour cell lines. More relevant to this research
investigation, was the reported anti-inflammatory activity of aloin. Specifically, the inhibitory
activity of aloin on matrix metalloproteinases, which when excessively secreted, can lead to
the development of osteoarthritis and cancer metastasis. Aloin has also been reported to have
antiplasmodial activity, which was also investigated.
Aloin was synthetically transformed into several derivatives, which could be potentially useful
medicinal compounds. The choice of derivatives to be made was based upon (i) known
biologically active compounds (e.g. aloe-emodin) and (ii) interesting biologically active
functional groups (e.g. amines). These aloin derivatives include aloe-emodin, rheinal, rhein
and three amine derivatives. Homonataloin, an aloin-analogue, which was also isolated from
A. marlothii, was synthetically transformed into nataloe-emodin. These two compounds serve
as aloin structural analogues for the biological testing. Aloin and derivatives were
characterised using NMR, HR-MS, UV and IR, which allowed for their unambiguous
structural elucidation.
Aloin and derivatives were all tested for (i) possible inhibition towards MMP-2 and MMP-9,
which are the two most common MMPs in the blood, and (ii) antiplasmodial activity against
chloroquine sensitive Plasmodium falciparum parasites. Doxycycline, a clinical tetracycline
drug, was used as a reference compound for the biological assays, since it shares many
common structural features with aloin and derivatives. 11-(Piperidin-1-yl)chrysophanol and
11-(morpholin-1-yl)chrysophanol proved to be the most potent selective MMP-2 inhibitors.
11-(Piperidin-1-yl)chrysophanol was also found to be the most potent against P. falciparum
parasite, along with 11-(pyrrolidin-1-yl)chrysophanol. Aloin has been shown to be a cheap, easily obtainable lead compound that could facilitate the
production of a range of powerful medicinal drugs. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2008.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/192 |
| Date | January 2008 |
| Creators | Pillay, Adushan. |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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