This work involves the isolation, structural elucidation and the biological screening of compounds from the Madagascan Samadera madagascariensis and Toddaliopsis bremekampii from South Africa. Samadera madagascariensis Jussieu (locally known as "fatriana") belongs to the Simaroubaceae family and is endemic to Madagascar. The leaves of Samadera madagascariensis are used in Madagascar for the treatment of stomach aches and dysentry, and the juice of the fresh leaves is used to treat wounds and burns. Samadera madagascariensis leaves were investigated in this work for the presence of quassinoids and triterpenoids. Eighteen compounds, including seven quassinoids: samaderine A (i), the novel 5~,6-dihydrosamaderine A (ii), the novel 2chlorosamaderine A (iii), the novel samaderine DN (iv), samaderine B (v), cedronin (vi) and the novel 3,4~-dihydrosamaderine C (vii), and eleven triterpenoids: the novel protosamaderine A (viii), 1,2-dihydrobruceajavanin A (ix), chisocheton compound A (x), the novel protosamaderine B (xi), the novel protosamaderine C (xii), the novel protosamaderine D (xiii), the novel protosamaderine E (xiv), the novel protosamaderine F (xv), the novel protosamaderine G (xvi), the novel protosamaderine H (xvii) and the novel protosamaderine I (xviii) were isolated from the Samadera madagascariensis leaves. The quassinoids isolated in this work are of the C18 and C19 classes, and only five of the C18 type have been published previously. Quassinoids exhibit a range of biological activities such as antileukemic, antiviral, antimalarial, anti-inflammatory, antifeedant and amoebicidal. 2-Chlorosamaderine A (iii), cedronin (vi) and 3,4~-dihydrosamaderine C (vii) were found to have anticarcinogenic properties. The triterpenoids isolated in this work are of the protolimonoid type and protolimonoids are known to exhibit anticarcinogenic and antifungal properties. Toddaliopsis bremekampii I. Verd. belongs to the Rutaceae family. Members of the Toddaliopsis genus are found in the warmer regions of southern Africa. The phytochemistry of this species and genus has not been investigated previously, however, other members of the Rutaceae have yielded a wide range of alkaloids and other compounds. The leaves and branches of Toddaliopsis bremekampii were investigated in this work and yielded four novel acridone alkaloids: 1,2,3trimethoxyacridone (i), 1,2,3-trimethoxy-1 O-acetoxymethylacridone (ii), 1-hydroxy-2,3-dimethoxy10- acetoxymethylacridone (iii) and 1,2,3-trimethoxy-1 O-methoxy methylacridone (iv). Acridone alkaloids are known to have antineoplastic and antitumour properties. These alkaloids were active in the chemiluminescence assay, which showed the suppression of the reactive oxygen species generated by polymorphonuclear leukocytes (PMNs) in humans. The PMNs play a key role in the host's defence. However, the reactive oxygen species generated as a result of this defence mechanism cause tissue damage. / Thesis (Ph.D.)-University of KwaZulu-Natal, 2004

This work describes the isolation and structural elucidation of extractives from four species of the Meliaceae and one of the Simaroubaceae families. All five species examined are endemic to the island of Madagascar. One novel seco-ring A protolimonoid with a bourjotinolone A-type side-chain was isolated from Turraea sericea, while Malleastrum antsingyense yielded one known and one novel limonoid of the vilasinin group. Neobeguea leandreana was found to contain three novel limonoids of the phragmalin class, including a relatively rare 17-keto seco-ring D compound and one containing a oxidized C-19 methyl group. Quivisia papinae has afforded eight novel and five known protolimonoids and limonoids of the azadiradione, evodulone, and mexicanolide classes. Included among these are a mexicanolide group limonoid with a 17-keto seco-ring D, and two further mexicanolide limonoids containing a hitherto unreported 9a,11a-epoxide ring and a Δ 9(11)-double bond. One C19 and four C20 quassinoids, of which one is novel, together with a known but rare triterpenoid, were isolated from the Madagascan Simaroubaceae Samadera madagascariensis. These findings support the suggestion that this species is closely related to, if not synonymous with, the companion species Samadera indica and Quassia indica. A literature survey on the effect of structural variations in ring B on coupling constants in 11,12-disubstituted havanensin-group limonoids was also undertaken, resulting in the observation of a remarkable correlation between ring structure and coupling constant values for a wide range of compounds isolated from different sources. An explanation for these observations is advanced. / Thesis (Ph.D.)-University of Natal, Durban, 2001.

This work is an account of investigations into the chemistry of members of the Amaryllidaceae and Hyacinthaceae families. The plants of the family Amaryllidaceae are a large group comprising over sixty genera and more than a thousand species. They are widely distributed, but are found more richly in the tropics, with a particularly high density in South Africa, with smaller centers of diversity in Andean South America and the Mediterranean. Amaryllidaceae plants have been extensively used by local traditional healers and have been reported to have numerous pharmacological uses. The alkaloids isolated from this family are a group of isoquinoline alkaloids found exclusively in this family. Plants belonging to two Amaryllidaceae genera were investigated phytochemically, one from each of the sub-tribes Crinineae and Amaryllidineae were investigated phytochemically. Brunsvigia natalensis is used in local traditional medicine to "straighten bones of children", treat barrenness in women and ease childbirth. This is the first phytochemical investigation of Brunsvigia natalensis, and yielded two new alkaloids, a new ceramide type compound and a known flavanoid. A comparative phytochemical investigation was carried out on the bulbs and seeds of Crinum stuhlmanni, which resulted in a number of different alkaloids being isolated from the seeds and bulbs of this plant. The southern African Hyacinthaceae is a large and chemically morphologically diverse group of plants. This family comprises approximately sixty-seven genera and nine hundred species worldwide, of which twenty-seven genera and three hundred and sixty - eight species are found locally. There are five sub-families of which three occur in southern Africa. The chemical constituents of this family can be divided into four classes, namely homoisoflavanones, steroidal compounds, bufadienolides and miscellaneous compounds. These plants are used in local traditional medicine for treating ailments such as hangovers, rheumatic fever, sprains and even cancer. The phytochemistry of three Hyacinthaceae plants was studied. The phytochemical investigation of Drimia macrocentra and Urginea riparia yielded a novel bufadienolide glycoside. These glycosides are quite unusual with the glycone attached to the aglycone at C-2 and C-3 and this has only been reported only once before in this family. The phytochemical investigation of Ledebouria revoluta yielded a number of homoisoflavanones. These homoisoflavanones have been shown to have anti-inflammatory activity and all of the compounds isolated in this work have been screened for this activity. Structural elucidation was carried out using spectroscopic methods such as NMR, MS, UV and IR. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2004.

Part A of this thesis is an account of the extractives isolated from one member of the Melianthaceae and two members of the Meliaceae. Plants belonging to these families are known to produce compounds with medicinal applications. Crude extracts from these plants are known to be widely used in traditional medicine. Structural elucidation was facilitated by the use of infrared, mass and nuclear magnetic resonance spectroscopic techniques. Three 20(29)-lupene type compounds (two known and one knew) were isolated from the bark of Bersama swinnyi (Melianthaceae); oleanolic acid was isolated from the leaves. The Meliaceae family is only represented b~ one species, Dysoxylum spectabile, in New Zealand. Two diterpenoids and two limonoids were isolated from the bark. The extracts of the rootbark and stembark of the hitherto uninvestigated species Turraea holstii (Gurke), supplied by Professor H. S. Rajab, Moi University, Kenya, were examined. Eight limonoids and a protolimonoid were isolated from the rootbark. A limonoid and a protolimonoid were isolated from the stembark. Some of the compounds isolated were found in both extracts. Four of the eight limonoids isolated were of the neotrichilenone type. The spectra for the compounds discussed in this text are presented in a separate book. / Thesis (Ph.D.)-University of Natal, 1997.

Plants have formed the foundation of traditional medicine systems throughout the world for thousands of years and continue to provide mankind with new remedies for various ailments. A large portion of the black South African population still depends on medicinal plants as primary health care due to its affordability, accessibility and cultural importance. These medicinal plants need to be investigated since new lead compounds are often found in nature. Homoisoflavanones isolated from South African and Indian plants were found to exhibit anti inflammatory activities although the mechanism of action has not yet been determined. A few reports on the anti fungal activities of these compounds were also found. Four new and three known homoisoflavanones of the 3-benzylidene-4-chromanone type were synthesized and tested for anti-inflammatory and antifungal activities. Two novel intermediates were also synthesised. Enantiomers of a homoisoflavanone of the 3-benzyl-4- chromanone types were also synthesized from the corresponding 3,5-dimethoxy phenol via 4- chromanone in six steps. This is the first report of the synthesis of an enantiomerically pure homoisoflavanone compound together with its opposite isomer. The enantiomers and racemate were tested for anti-inflammatory activity. All the synthesized homoisoflavanones were screened for cytotoxicity. The structures of these homoisoflavanones were elucidated by NMR spectroscopy along with HRMS data. The crystal structure of a homoisoflavanone with anti-inflammatory and antifungal activity is reported. The anti-inflammatory activity of the homoisoflavanones was determined in an acute croton oil-induced auricular dermatitis mouse model. The antifungal activity was performed in vitro against a Candida albicans strain. Compounds were tested for cytotoxicity against a Chinese Hamster Ovarian (CHO) cell line using the 3-(4,5-dimethylthiazol-2-yl)-3,5- diphenyltetrazoliumbromide (MTT) assay. In conclusion, the synthetic homoisoflavanones showed anti-inflammatory as well as antifungal activity. Some of the compounds showed anti-inflammatory activity comparable to that of the commercially available diclofenac. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2011.

Background and Aims of Study. Scilla nervosa is a member of the Hyacinthaceae plant family that has been naturalised in the grasslands of Southern Africa. The bulbs are traditionally used to treat a variety of ailments. For example, the Zulu people use aqueous decoctions of the bulbs as analgesics in the treatment of rheumatic fever, crushed bulbs are used by the Sotho people as laxatives and the Tswana people use cooked bulbs to treat infertility in women as well as cold aqueous extracts to treat infections. It was recently demonstrated in our laboratory that extracts prepared from the bulbs possess potent anti-inflammatory properties, and this may therefore provide a rationale for the traditional use of the plant as an analgesic. Several studies have demonstrated that the bulbs contain homoisoflavanones and stilbenoids that could be responsible for their therapeutic effects. Although the plant has diverse medicinal applications, and despite it being recognised as a poisonous species particularly in livestock, little is known about its toxicity in human liver cells. The objectives of this study were therefore to investigate the potential toxicity of the bulbs on the liver, a major detoxifying organ. A human liver cell line was treated with an aqueous extract of the bulbs to investigate (1) cell viability, (2) potential mechanisms of cytotoxicity, (3) DNA integrity, and (4) changes in the cytochrome P450 enzyme activity. Materials and Methods. This study was conducted on the cultured HepG2 human hepatocellular carcinoma cell line, a model system to investigate the cytotoxicity of xenobiotics. The viability of cultured HepG2 liver cells in the presence of varying concentrations of an aqueous extract of the bulbs was determined after 24 hours treatment, and the concentration that reduced viability to 50% (IC50) was derived. Potential mechanisms of cytotoxicity at the IC50 were investigated. These included changes in metabolic activity (intracellular adenosine triphosphate (ATP) quantification), apoptosis induction (phosphatidylserine (PS) externalisation, caspase-8 and -9 induction and changes in mitochondrial membrane potential), and oxidative damage via free radical formation (lipid peroxidation). Genotoxicity was investigated by determining changes in DNA integrity (DNA fragmentation). The ability of the extract to stimulate or {¹ Du Toit, K., Kweyama, A., Bodenstein, J. 2011. Anti-inflammatory and antimicrobial profiles of Scilla nervosa (Burch.) Jessop (Hyacinthaceae). South African Journal of Science, 107:96-100.} inhibit enzymes commonly involved with drug metabolism was investigated by determining cytochrome P450 3A4 (CYP3A4) activity. Results Cell-viability decreased in a concentration-dependent manner and the IC50 was determined as 0.03 mg/ml. Treating the cells at the IC50 resulted in (1) a 1.2-fold increase in intracellular ATP levels, (2) no significant change in PS externalisation, (3) a 1.3-fold increase in caspase-8 activity, (4) a 1.1-fold decrease in caspase-9 activity, (5) no significant change in mitochondrial membrane potential, (6) a 1.9-fold increase in lipid peroxidation, (7) evidence for genotoxicity as demonstrated by DNA fragmentation, and (8) no evidence of changes in CYP3A4 activity. Conclusion. Results suggest that HepG2 liver cells are sensitive to an aqueous extract of the bulbs of S. nervosa. The extract has the potential to (1) induce apoptosis, (2) increase oxidative stress and (3) cause genotoxicity in vitro. peroxidation, genotoxicity / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2011.

M.S.

Thesis (M.Tech.: Biotechnology)-Dept. of Biotechnology, Durban University of Technology, 2007 xv, 136 leaves / The chemical and biological properties of the essential oil from Cymbopogon validus were investigated. Hydro-distillation was used to extract the oil from C. validus, the flower-heads, leaves, culms and rhizomes. The percentage oil yields obtained from the plant organs varied from 0.05 to 1.23%, with the greatest concentration found in the flower-heads and rhizomes, 1.23 and 1.12% respectively. A sensory evaluation of the oil revealed that the essential oil was slightly murky, pale yellow in colour, had a strong turpentine-like smell and remained liquid at room temperature. The oxidative stability of C. validus oil was evaluated by determining its Rancimat induction period (negative), peroxide value (60.56 meq/kg), iodine value (84.55), percentage free fatty acids (0.19%) and percentage cholesterol (3.03%). These results indicated that the oil was highly susceptible to oxidation. Chromatographic profiles of the oils from C. validus, as well as the plant organs were generated using gas chromatography-mass spectroscopy (GC-MS). Predominant compounds present in the oil included alpha-Cubebene, Camphene, Geraniol, Limonene, Myrcene, Palmitic acid and Sabinene. C. validus essential oil was also investigated for its antimicrobial (disk diffusion), antioxidant (1, 1-Diphenyl-1-Picrylhydrazyl (DPPH) assay), anti-inflammatory (5-lipoxygenase assay), anti-mosquito properties (insecticidal, larvicidal and repellency assays) and toxicity profile (Brine shrimp and Ames assays). The oil showed poor antimicrobial activity and inhibited the growth of only Gram positive bacteria with a minimum inhibitory concentration (MIC) of 0.0625 (vol/vol) for Bacillus, Micrococcus and Staphylococcus species. The oil also exhibited excellent antioxidant activity, scavenging more than 80% of DPPH free radicals and possesses anti-inflammatory activity (IC50=190 ppm). C. validus oil showed good adulticidal activity (53.7% mortality) and excellent larvicidal (100% mortality) and repellent activity (100% repellency) against Anopheles arabiensis mosquitoes. At high concentrations, the oil was toxic to brine shrimp larvae. However, when diluted it was safe and the minimum inhibitory concentration was 0.0001(vol/vol). The absence of revertant colonies at all essential oil concentrations in the Ames test suggest that the oil is not mutagenic. These results lead the way for exploiting C. validus oil as a multi-functional agent that has antibacterial, anti-oxidant, anti-inflammatory, and anti-mosquito properties.

The Best M.Phil Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,1995-1997 / published_or_final_version / Chemistry / Master / Master of Philosophy

Three plant species (Phylica paniculata Willd., Pergularia daemia Forssk. and Monsonia / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2006.