Hermannia incana Cav. (Sterculiaceae), known as sweet yellow bells, is a medicinal plant used by the people of the Eastern Cape for the treatment of stomach-ache and diarrhoea. It has purgative and diaphoretic effects. It is a prostrate herb with yellow flowers and sparsely hairy and slightly glandular leaves, occurring in grassland and marshes in the Eastern Cape Province of South Africa. Based on the ethnomedical uses of this plant, the research project was designed to evaluate its antidiarrhoeal and toxicological properties. An ethnobotanical study of plants used for the treatment of diarrhoea in the Eastern Cape Province was carried out, using a questionnaire which was administered to herbalists, traditional healers and rural dwellers. This survey indicated a total of 17 plant species from 14 families. Elephantorrhiza elephantine (Burch.) Skeels, Hermannia incana Cav., Pelargonium reniforme Curt., Alepidea amatymbica Eckl. & Zeyh. and Bulbine latifolia (L.f.) Roem. et Schult. were the most frequently mentioned and highly recommended plants for the treatment of diarrhoea by both the traditional healers and rural dwellers. The root, bark and leaves are the common parts of plants used, while decoctions and infusions are the main methods of preparation. The agar dilution method was used to study the antimicrobial activity. The methanol extracts of the plant showed appreciable activity against Gram-positive and Gram-negative bacteria at concentrations ranging from 0.5 to 7.0 mg/ml. The acetone and water extracts of both the leaves and the roots showed moderate activity against Gram positive bacteria and less activity against Gram negative bacteria. All the extracts inhibited the growth of the fungi Aspergillus flavus, Aspergillus niger, and Mucor hiemalis with growth inhibition ranging from 54.31 percent to 96.67 percent at 0.1-10 mg/ml. None of the extracts suppressed the growth of Candida albicans at the maximum concentration (10 mg/ml) tested. iii In the in vivo antidiarrhoeal evaluation using Wistar rats, the aqueous extract at all the doses tested, significantly prolonged the time of induction of diarrhoea and also reduced the frequency of diarrhoeal episodes and fecal parameters (total number, number of wet, fresh and dry weight and water content of the faeces). The percentage inhibition of defecation and intestinal content (enteropooling) were increased in dose dependent manner. The doses also reduced the intestinal transit time of charcoal, masses and volumes of intestinal fluid (gastrointestinal motility). These results are indications of antidiarrhoeal property of H. incana leaf extract with the 600 mg/kg body weight of the extract being the most effective. In the toxicological evaluation using Wistar rats, the oral administration of the extract did not produce any significant effect on the liver and kidney body weight ratios, RBC, HB, PCV, MCV MCH, MCHC, RCDW, WBC, neutrophils, monocytes and basophils cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and atherogenic index. The extract also did not affect the levels of sodium, potassium, chloride, inorganic phosphorus, urea, creatinine, total protein, globulin, albumin, total and conjugated bilirubin. The activities of alkaline phosphatase, gamma glutamyl transferase and alanine aminotransaminase in the serum were increased by the extract whereas aspartate aminotransaminase was decreased. The levels of LUC, platelets, lymphocytes and eosinophils were significantly affected at 600 mg/kg body weight. The available evidence in this study suggests that the extract of H. incana leaf is mild, parameter and dose specific. The structure and distribution of foliar appendages on the leaves of this plant were investigated with the JEOL (JSM-6390LV) scanning electron microscope (SEM). Both glandular and non-glandular trichomes were observed. Long stalked glandular trichomes were present on both the abaxial and adaxial surfaces while short stalked glandular trichomes were present only on the adaxial surface. Glandular trichomes were capitate while nonglandular trichomes were stellate with many arms. Energy dispersive X-ray spectroscopyiv SEM showed that Al, Ca, K, Na, Ti and Si were the major constituents of the crystals analyzed from the leaf surfaces. The phytochemical screening of H. incana revealed the presence of bioactive antidiarrhoeal agents such as alkaloids, tannins, saponins, phenolics, triterpenes, cardiac glycosides, flavonoids, cardenolides and dienolides. Two flavonoids, epicatechin and 3, 5, 7, 2’ tetra-hydroxy flavone-3- O--D-glucopyranoside were isolated from the leaves of the plant through bio-active guided fractionation. Both these compounds were screened against diarrhoea causative organisms (Echerichia coli, Shigella flexneri, Bacillus cereus and Staphylococcus aureus) and exhibiting minimum inhibitory concentrations ranging from 12.5 to 100 μg/ml. The findings from this research have generally justified the traditional use of this plant for the treatment of diarrhoea in this province.

D.Phil. / The objective of the research described in the first part of this thesis was to develop a general method utilising palladium catalysed reactions for the synthesis of the anti-cancer compound, lavendamycin and analogs thereof. Therefore, the development of a general route to synthetic euivalents of the lavendamycin AB quinoline system, 2-hydroxyquinolines, with potential for coupling to the CDE or CD moiety, was addressed. The first protocol for the synthesis of 2-hydroxyquinolines invloved to the use of appropriately substituted o-nitrophenyltriflates (readily prepared from phenols) in a Heck reaction under neutral conditions followed by a one-pot reduction and cyclisation step. The synthetic potential of such an approach was demonstrated by the preparation of a suitable lavendamycin AB synthon from commecially avalaible guiacol. A second general strategy towards the synthesis of the AB synthon utilising a performed ring system commecially available 8-hydroxyquinoline has been successfully developed. This approach requiring the introduction of a suitable leaving group in the 2-position involved the following sequence of reactions: protection of 8-hydroxyl group N-oxidation, and a rearrangement step. This methodology yielded five different key intermediates all possessing suitable functionality in the 2 position which would allow further cross-coupling to an appropriate CDE ring equivalent.

Please read the abstract in the section 07chapter7 of this document / Thesis (DPhil (Plant Physiology))--University of Pretoria, 2007. / Plant Science / unrestricted

Submitted in fulfillment of the requirements for the Degree of Master of Technology: Biotechnology, Durban University of Technology, 2009. / Dichrostachys cinerea, Carpobrotus dimidiatus, Capparis tomentosa and Leonotis leonurus are all plants that are indigenous to South Africa. These plants are used in traditional medicine to treat various ailments. However, there is little or no scientific data to justify these traditional uses. Furthermore, it is difficult to reconcile traditional knowledge with scientific evidence because of the overwhelming targeting of signal-responsive systems by plant defensive compounds, multiple sites of action and the connectedness of the signaling pathways, which provide many cures and have pleiotropic effects. In order to evaluate the action spectrum of these plants, and validate its widespread use, this research evaluated the antibacterial, antioxidant, anti-inflammatory, anti-mosquito and immunomodulatory properties of these plants. Antimicrobial activity of the extract was determined by evaluating the bactericidal and fungicidal action using the agar disc diffusion assay. Anti-oxidative properties of the extracts were tested using the DPPH photometric assay. Anti-inflammatory properties were carried out using the 5-lipoxygenase assay. The larvicidal, repellency and insecticidal assay was determined against A.arabiensis. The safe use of these plant extracts was determined by evaluating toxicity, a brine shrimp lethality assay and an in vitro cell culture system using human myelogenous leukemia cell line. Potential carcinogenic activity was evaluated using the Ames Salmonella Mutagenecity assay. The immunomodulatory activity of the extracts on human peripheral blood mononuclear cells 6 was evaluated on freshly harvested lymphocytes using the MTT assay. Cytokine response was evaluated by measuring the secretion of interferon-gamma and interleukin-10. Elucidation of the B cells, T cells, activated T cells, CD 4+, CD 8+ and NK cells was performed by flow cytometry. The extracts showed anti-microbial activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Salmonella typhimurium, Serratia marcescens, Bacillus cereus and Tricoderm sp. The highest activity was shown by methanolic and aqueous extracts of L. leonurus leaves followed by methanolic and aqueous extracts of D. cinerea. Extracts of C. tomentosa and D.cinerea demonstrated a higher degree of free radical scavenging than rutin, which was used as a standard indicating that these plants have strong antioxidant properties. None of the plants showed significant anti-inflammatory activity when compared to NDGA. In the anti-mosquito assays, the extracts showed strong repellency and insecticidal activity. L. leonurus extracts demonstrated the highest insecticidal and repellency activity against the mosquito, and was also found to cause ‗knockdown‘ and mortality. The extracts display no toxicity, cytotoxicity and mutagenicity. The immunological studies for immune modulation showed that the methanol extracts of these plants induce a Th1- predominant immune response because they significantly suppressed the secretion of IL-10 and augment IFN-γ production, which are hallmarks used to indicate a stimulation of the innate immune response. This study also provides new information, with respect to the potential use of these plants in producing a mosquito repellent and an immunostimulant. / National Research Foundation

Candida species were discovered more than a century ago as a causative organism of oral thrush. In HIV patients, the presence of oral candidiasis has been shown to be the earliest opportunistic infection. Candidiasis lesions associated with HIV infections are primarily a reflection of the specific change of the host's immune response caused by the virus. Studies of AIDS all over the world show that 58-81% of all patients contract a fungal infection at some time during the primordial stage or after developing AIDS and 10-20% have died as a direct consequence of fungal infections. Twenty four South African medicinal plants were screened using a modification of the NCCSL broth microdilution antifungal test against Candida albicans standard strain ATCC 10231 and two clinical isolates from a 5-month- old baby and an adult. This assay was performed in order to find a traditional remedy to treat oral candidiasis. Of all the screened plants Allium sativum L., Glycyrrhiza glabra L., Polygala myrtifolia L. and Tulbaghia violacea L. aqueous extracts were found to have the best activity. Allium sativum and Tulbaghia violacea aqueous bulb extracts had MIC values of 0.56 mgml-1 and 3.25 mgml-1 respectively, whilst Polygala myrtifolia leaf extracts and Glycyrrhiza glabra rhizome extracts had MIC values of 1.56 mgml-1 and 3.25 mgml-1 respectively when tested against the isolate from a 5-month-old baby, which was the most susceptible of the isolates used. All the extracts had higher MIC values against the standard strain (ATTC 10231), which was the least susceptible to the extracts used. Stability testing was performed on fresh aqueous extracts of A. sativum, G. glabra, T. violacea and P. myrtifolia stored at 4°C, 23°C and 33°C over a period of one week, to determine the stability of the extracts in solution. All A. sativum extracts maintained stability for three days in solution, whilst T. violacea extracts remained stable for only two days in solution. TLC fingerprinting of A. sativum and T. violacea extracts indicated the presence of the known antibacterial and antifungal compound allicin. The activity of allicin and other active compounds was observed by using the bioautographic assay, which was performed on these extracts. P. myrtifolia and G. glabra extracts lost stability 24 hours after preparation at all tested temperatures. However, it was clear with the four plant extracts tested that storage of solutions at higher temperatures reduced their activity and stability. The unpleasant taste and smell of A. sativum and G. glabra could however not be masked, since the intake of these two extracts would result in HIV patients being recognised. These two plants where therefore not considered for further investigation. G. glabra and P. myrtifolia are both saponin containing plants. These could be the active constituents responsible for the anticandidal action. G. glabra is known for its biological activity as an antibacterial agent, whilst other Polygala species have been reported to possess antifungal saponins. Although P. myrtifolia and G. glabra are not stable for more than 24 hours, they do not have an unpleasant smell or taste. These plants are therefore further investigated for use as oral mouthwash in clinics and homes. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 2003.

In most countries, as many as 15 to 25% of the adult population have raised blood pressure. People with hypertension, and even those with mild elevation of blood pressure, are at an increased risk of cardiovascular disease, whether or not the symptoms are present. The risk of serious cardiovascular disease varies greatly among individuals and is also determined by a variety of concomitant risk factors other than the level of blood pressure. Hypertension develops as a result of disturbances of the body's blood pressure regulating system. The biological activity of the renin-angiotensin systems results from a series of specific enzymatic cleavages leading to the generation of angiotensin II, a potent vasoconstrictor. In the treatment of hypertension, inhibition of the angiotensin converting enzyme is established as one modern therapeutic principle. Angiotensin converting enzyme inhibitors act by inhibiting the conversion of angiotensin I to angiotensin II. The in vitro assay, developed by ELBL and WAGNER (1991) for the detection of angiotensin converting enzyme inhibitors in plant extracts was successfully established during this study. Plants used by traditional healers in South Africa for the treatment of high blood pressure were investigated for their antihypertensive properties, utilizing the established angiotensin converting enzyme assay. Twenty plants were investigated for their angiotensin converting enzyme inhibitory activity. The highest inhibition (97%) was obtained by Adenopodia spicata leaves. A further seven plants exhibited an inhibition greater than 70% and five more over 50%. Plants exhibiting inhibition levels greater than 50% were further tested for the presence of tannins in order to eliminate possible false positives. The leaves of Tulbaghia violacea were chosen for bioassay-guided fractionation in an attempt to isolate the active compound(s). Serial extractions were made of ground Tulbaghia violacea leaves using polar to non-polar solvents to establish the solvent giving optimum extraction of the active compound(s). Distilled H2O was selected as the extractant and a bulk extract was performed on 0.7 kg ground leaves. The extracted residue was partitioned against butanol, fractionated using cation exchange resin chromatography, Sephadex ® LH-20 and high performance liquid chromatography. Fractions collected after each purification step were assayed using the angiotensin converting enzyme assay. Fractions exhibiting high levels of angiotensin converting enzyme inhibition were selected for further purification. The active fraction from the final high performance liquid chromatography step used in this study requires further attention in order to purify and identify the active compound(s). The chromatographic and chemical properties of the compound(s) present in the isolated active fraction are discussed. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1998.

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.

No abstract available. / Thesis (M.Sc.)-University of Natal, Durban, 2001.

This work is an account of investigations into the chemistry of one of the members of the Amaryllidacae family, Ammocharis coranica, and one of the members of the Fabaceae family, Sophora velutina. Chapter one is an account of the extractives from the bulbs of Ammocharis coranica. In all, twelve compounds, eight alkaloids and four cycloartane compounds have been isolated of which one alkaloid and one cycloartane compound have not been described previously. Plants belonging to the Amaryllidacae family have been used by traditional healers, especially in Africa, to treat a range of illnesses and diseases. The alkaloids isolated from these plants have been shown to exhibit responses to muscle stimulant, antiviral, antifungal, antiyeast, antimalarial, cytotoxic and antitumoural activities. Ammocharis coranica is used by the Zulu tribe in South Africa to treat any illness believed to be caused by witchcraft. Alkaloids from the three most common types among the isoquinoline group were found in this species. These are lycorine, 1-O-acetyllycorine, hippadine, acetylcaranine, and the novel 1-O- acetyl-9-norpluviine from the lycorine type, 6-α-hydroxypowelline from the crinine type and hamayne and crinamine from the haemanthamine type. Cycloartane compounds have not been reported previously from the Amaryllidaceae family. All four cycloartane compounds had a common side chain, containing an olefinic methylene group at position 24, but differed in their substituents at positions 3 and 4. These compounds were found to be 24-methylenecycloartan-3β-ol, cycloeucalenol, cycloeucalenone and the novel compound 4-methylenepollinastanone. Chapter two is an account of the extractives from the seeds of Sophora velutina. The seeds of other Sophora species have been used in traditional ceremonies by the Indians of the Southwest United States and adjacent Mexico because of their hallucinogenic activity. The seeds of Sophora velutina subsp. zimbabweensis found in Zimbabwe are suspected to have historically been used by the natives for their hallucinogenic properties. These plants have been known to contain several quinolizidine alkaloids, flavonoids and isoflavonoids. One alkaloid, N-methylcytisine and two isoflavones, pseudobaptigenin and calycosin, as well as the common phytosterol, β-sitosterol were isolated from the seeds of this species. N-methylcytisine is a common quinolizidine alkaloid, isolated previously from several Sophora species and pseudobaptigenin and calycosin are well known isoflavones, isolated previously from several species in the Fabaceae. / Thesis (M.Sc.)-University of Natal, Durban, 1999.

This thesis describes a phytochemical investigation of four medicinal plants, namely, Agave attenuata (Agavaceae), Balanites maughamii (Balanitaceae), Astrotrichilia parvifolia (Meliaceae) and Combretum fragrans (Combretaceae). Investigations of A. attenuata and B. maughamii were undertaken as biological studies have shown that these plants possess anti-bilharzial properties. Schistosomiasis is an important public health issue in South Africa and attempts to deal with infected rural communities have forced scientists to focus their attention on snail control using plant molluscicides. A. attenuata yielded two glycosides, timosaponin A III (compound I) and 5?-pregn-16-en-20one- 3?-O-tetrasaccharide (compound II), while a coumarin, scopoletin (compound III) and a sterol, stigmasterol (compound IV) were isolated from B. maughamii A dammarane, shoreic acid (compound V) was isolated from A. parvifolia, this formed part of an ongoing investigation into the Meliaceae of Madagascar. Plants of the family Combretaceae are widespread in Africa and are used by traditional healers for a wide range of illnesses. The leaves and bark are used abundantly, however, the winged fruits are never eaten as they are highly toxic to animals and humans. The leaf surface is covered with epidermal scale-like trichomes through which acidic triterpenoid mixtures are secreted. Six lupane-type triterpenoids were isolated from C. jragrans, namely, lupeol (compound VI), lupenone (compound VII), lupeol 3?- docosanoate (compound VIII), lupeol 3?-eicosanoate (compound IX) hennadiol (compound X) and 30hydroxylupenone (compound XI). All the above compounds were isolated by column chromatography and the structures were elucidated by means of NMR spectroscopy, mass spectrometry and infra red spectroscopy. / Thesis (M.Sc.)-University of Natal, Durban, 2000.