published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Wong Man-po. / Thesis (M. Phil.)--Chinese University of Hong Kong, 1980. / Bibliography: leaves 88-91.

Forty-six constituents have been identified from an ethanol extract prepared from the aerial parts of Desmodium styracifolium, including seven triterpenes: lupeol (15), lupeone (16), olean-12-ene-3beta, 22beta-diol (sophoradiol) (19), olean-12-ene-3beta, 22beta, 24-triol (soyasapogenol B) (20), (23Z)-9, 19-cycloart-23-ene-3beta, 25-diol (21), (24R)-cycloart-25-ene-3beta, 24-diol (24a), and (24S)-cycloart-25-ene-3beta, 24-diol (24b); one triterpene saponin: 3-O-[alpha-rhamnopyranosyl (1→2)-beta-galactopyranosyl (1→2)-beta-glucuronopyranosyl] soyasapogenol B (soyasaponin I) (53); three phytosterols: beta-sitosterol (17), stigmasterol (18), and daucosterol (47); sixteen isoflavanones and O-glycosides: 5, 7-dihydroxy-2', 4'-dimethoxy-isofavanone (homoferreirin) (22), 5, 7, 4'-trihydroxy-2'-methoxy-isofavanone (isoferreirin) (23), (3R)-5, 7-dihydroxy-2', 3', 4'-trimethoxy-isoflavanone (25a), (3S)-5, 7-dihydroxy-2', 3', 4'-trimethoxy-isoflavanone (25b), (3R)-5, 7-dihydroxy-2'-methoxy-3', 4'-methylenedioxy-isoflavanone (26a), (3S)-5, 7-dihydroxy-2'-methoxy-3, 4'-methylenedioxy-isoflavanone (26b), 5, 7, 3'-trihydroxy-2', 4'-dimethoxy-isoflavanone (secundiflorol H) (40), 5, 7, 2', 4'-tetrahydroxy-isoflavanone (dalbergiodin) (41), 3, 5, 7, 4'-tetrahydroxy-2, 2'-epoxyisoflavanone (42), (3R)-5, 7-dihydroxy-2', 3', 4'-trimethoxy-isoflavanone 7-O-beta-glucopyranoside (48a), (3S)-5, 7-dihydroxy-2, 3', 4'-trimethoxy-isoflavanone 7-O-beta-glucopyranoside (48b), (3R)-5, 7-dihydroxy-2'-methoxy-3', 4'-methylenedioxy-isofavanone 7-O-beta-(glucopyranoside (49a). (Abstract shortened by UMI.) / In the present study, two medicinal plants were investigated for their organic constituents. Plant samples were extracted and purified by chromatographic separation using a combination of methods. Each compound isolated was characterized by spectroscopic and physical data. A number of new chemical structures were found. / The investigation has led to the isolation and structural elucidation of fourteen pure compounds from an ethanol extract prepared from the dried rhizomes of Alisa orientale, including three types of skeletons: protostane triterpene, guaiane sesquiterpene and phytosterol. They were identified to be beta-sitosterol (1), (17S)-3, 11-dioxo-23-nor protost-12-en-23 (17)-olide (2), alisol B 23-acetate (3), alismol ( 4), alismoxide (5), alisol B (6), alisol A (7), 25-O-methylalisol A (8), 25-anhydroalisol A 24-acetate (9), 25-anhydroalisol A (10), alisol E 23-acetate (11), daucosterol 6'-stearate (12), (20R, 23S, 24R)-23, 24, 25-trihydroxy-2, 3-seco protost-13 (17)-en-3-oic acid 2, 11beta-lactone (13), and 13beta, 17beta-epoxyalisol A (14). Among them, compound 2 was a new naturally occurring skeleton of 23-nor protostane triterpene, and compound 13 a new 2, 3-seco-protostane triterpene. / Zhao Ming. / "September 2005." / Adviser: Chun-Tao Che. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3812. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 179-187). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

In this study, two plant species, Schefflera umbellifera (Araliaceae) and / Thesis (M.Sc.) - University of KwaZulu-Natal, Pietermaritzburg, 2007.

Adverse effects and increasing cost of therapeutic drugs have renewed an interest in the use of medicinal plant products for the treatment of a variety of chronic disorders. One such bioactive plant-derived compound is a pentacyclic triterpenoid, oleanolic acid (3ß-hydroxy-olea-12-en-28- oic acid, OA) present in herbs. OA possesses a variety of pharmaceutical activities and of interest in this study are the anti-diabetic properties. Diabetes is associated with disorders grouped as microvascular (retinopathy and nephropathy) and macrovascular (atherosclerotic) complications. Accordingly, this study further investigated the potential of OA in diabetes management by studying the effects of this triterpene on kidney function as well as proximal tubular Na+ handling in an effort to identify the site of action of OA. Furthermore, the study evaluated the effects of OA in kidney and liver cell lines to establish whether this triterpene exhibits any toxicity in these organs. OA was extracted using a previously validated protocol in our laboratory. Briefly, dried flower buds of Syzygium aromaticum were soaked in dichloromethane overnight, thereafter in ethyl acetate to obtain ethyl acetate solubles which contained a mixture of OA/ursolic and maslinic acid (MA). OA/MA mixture was subjected to column chromatograph and pure OA was obtained through recrystallization in methanol. The absolute stereostructure of OA was elucidated using 1H and 13C NMR spectroscopy and was comparable to previously reported data. In kidney function studies, various doses of OA (30, 60, 120 mg/kg, p.o.) were administered to male Sprague-Dawley rats twice (8h apart) every third day for five weeks. Rats administered deionised water served as controls. Measurements of body weight, food and water intake, blood pressure, Na+, K+, Cl-, urea and creatinine were taken 24 h from dosing. Renal clearance studies investigated the influence of OA on Na+ handling in the proximal tubule of anaesthetized rats using lithium clearance. Animals were given water with lithium (12mmol/l) for 48 hours following which they were anaesthetized and cannulated using a previously validated standard protocol that has been reported from our laboratories. After a 3½ h equilibration, animals were challenged with hypotonic saline for 4 h of 1 h control, 1½ h treatment and 1½ h recovery periods. OA was added to the infusate during the treatment period. In vitro effects of various OA concentrations (5, 10, 20, 40, 80 μmol/l) were investigated in HEK293, MDBK and HepG2cell lines. Cells were exposed to OA for 24, 48 and 72 h, thereafter, 3-4,5 dimethylthiazol-2-yl- 2,5diphenyltetrozolium bromide (MTT) and single cell gel electrophoresis (comet) assays were conducted. All data are presented as means ±SEM. OA significantly (p<0.05) increased urinary Na+ output from week 2 until the end of the experimental period in a dose independent manner. However, this OA-evoked natriuresis was not reflected in plasma collected at the end of the experiment as there was no change in plasma Na+ concentrations compared with control animals at the corresponding time. OA administration had no significant influence on K+ and Cl- excretion rates throughout the experiment. However, OA significantly (p<0.05) reduced plasma creatinine concentration with a concomitant increase in glomerular filtration rate (GFR). Furthermore, OA administration significantly (p<0.05) decreased mean arterial pressure from week 2 until the end of the experimental period. Intravenous infusion of OA at 90 ug/h for 1 ½ h induced a marked increase in urinary excretion rates of Na+. This increase was accompanied by concomitant increase in FENa proximal and FENa distal and FELi which persisted until the end of the experiment without any apparent changes in GFR. The cell viabilities of HepG2, HEK293 and MDBK cell lines were significantly increased after 24 h exposure, however, the viabilities of all the three cell lines dropped after 72 h exposure to values that did not achieve statistical significance in comparison to the respective controls. In addition, all OA-treated cells in the comet assay had intact DNA after exposure for 24, 48 and 72 h. Hence, the decrease in viability that was observed in the MTT assay after 72 h exposure could probably be attributed to the depletion of nutrients in the culture medium. The results of the present study, apart from confirming our previous observations of the natriuretic effects of OA in rats, indicate that this effect is in part mediated via the inhibition of proximal tubular Na+ reabsorption and increased Na+ secretion. We speculate that this increased Na+ secretion could have been due to increased tubular function and not to the toxicity of OA as indicated by MTT and comet assays. These findings suggest that OA does not exhibit toxicity in the kidney and the liver. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Westville, 2012.

The Hyacinthaceae family is richly represented in southern Africa. Of the five subfamilies, three are found in southern Africa. These are the Urgineoideae (URG), Ornithogaloideae (ORN) and the Hyacinthoideae (HYA). The overview of Pfosser and Speta (1999), revealed chemotaxonomic trends at a subfamily level for the Hyacinthaceae family of the Flora of southern Africa region. Homoisoflavanones were found to define the Hyacinthoideae subfamily whilst the Ornithogaloideae subfamily and the Urgineoideae subfamily are defined by steroidal compounds namely, cholestane glycosides and bufadienolide glycosides respectively. Representatives of all three subfamilies were investigated phytochemically. From Eucomis comosa (HYA), five homoisoflavanones were isolated. Omithogalum tenuifolium (ORN) contained a spirostanol saponin of which the crystals were amenable to X-ray analysis. Evidence of a novel stereoisomer was obtained. Extraction of the bulbs of Galtonia princeps (ORN) led to the isolation of two cholestane glycosides, one known and one novel, and a homoisoflavanone. Two novel bufadienolides were isolated from Urginea Iydenburgensis (URG). Structures were elucidated on the basis of spectroscopic data and chemical evidences. Homoisoflavanones and related compounds were then screened for antibacterial and anti-inflammatory activity. Several compounds showed antibacterial activity against Staphylococcus aureus, a gram-positive bacteria. Inhibition of the inflammatory process in microsomal cells was first evaluated, followed by screening of specific inhibition of cyclooxygenase enzymes. These are membrane-associated enzymes occurring in different isoforms. High levels of anti-inflammatory activity were detected especially in microsomal cells. This biological information made it possible to rationalize the ethnomedicinal use of some of the plants from which the compounds were isolated. 15 Biological screening was followed by a computer-based quantitative structureactivity relationship (QSAR) study. This study produced five equations with significant prediction value of anti-inflammatory and antibacterial activity for homoisoflavanones and related compounds. The derived models also provided valuable parameter guidelines of those properties influencing the antiinflammatory and antimicrobial activity of the studied compounds. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2004.

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.

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.