Biochemical evaluation of Tulbaghia violacea harv.rhizomes in diet induced hypercholestrolemic rats
- Authors: Olorunnisola, Olubukola Sinbad
- Date: 2012
- Subjects: Violaceae , Anticoagulants (Medicine) , Antineoplastic agents , Rats , Hypercholesteremia , Cardiovascular agents , Medicinal plants
- Language: English
- Type: Thesis , Doctoral , PhD (Biochemistry)
- Identifier: vital:11273 , http://hdl.handle.net/10353/d1006900 , Violaceae , Anticoagulants (Medicine) , Antineoplastic agents , Rats , Hypercholesteremia , Cardiovascular agents , Medicinal plants
- Description: Discovery of cheap, nontoxic and readily available antiatherosclerotic drugs is an extraordinary challenge in this modern world. Atherosclerosis and cardiovascular diseases have been predicted to be the leading cause of death by the year 2030. Hence, this thesis was designed to search for plant (s) with anti-atherogenic properties, investigate its possible side effects and extrapolate its likely mechanism(s) of action. An ethnobotanical survey was employed in identification of locally important plants used for the management and treatment of cardiovascular diseases and its predisposing factors in Nkonkobe Municipality, Eastern Cape in South Africa. Information on the names of plants, their parts used and methods of preparation was collected through a questionnaire which was administered to herbalists, traditional healers and rural dwellers. The most frequently used plant (Rhizomes of Tulbaghia violacea Harv.) was investigated for toxicity using brine shrimp lethality (in vitro) and in vivo toxicity test (acute and subchronic) on rats to determine safety dosage. The in vitro antioxidant and free radical scavenging activity of the plant was investigated using models such as 1,1-diphenyl-2- picrylhydrazyl (DPPH), superoxide anions, hydrogen peroxide (H2O2), nitric oxide (NO), 2,2’- azinobis [3-ethylbenzothiazoline-6-sulfonic acid] diammonium salt (ABTS), lipid peroxidation inhibition and the ferric reducing agent. Phytochemical content and the effect of oral administration of fresh methanolic extract rhizomes of Tulbaghia violacea (250, 500 mg/kg. bwt/day) on Lipid peroxidation (TBARS), serum and tissue antioxidant enzymes in normal, hypercholesterolemic and diet induced atherogenic rats were also assessed. More so, the potential of the extract (250 and 500 mg/kg. bwt) to protect against atherogenic diet (4 percentage cholesterol 1 pecentage cholic acid and 0.5 percentage thiouracil) induced fatty streaks formation, dyslipidemia, oxidative stress and endothelial dysfunction was also investigated. Ethnobotanical study revealed that 19 plant species are used for the treatment of heart related diseases in the Municipality. 53 percentage of the plants mentioned were used for the management of chest pain, 47 percentage for high blood pressure, 42 percent for heart disease, 16 percentage for stroke and 11 percentage for the treatment of hypercholesterolemia. Tulbaghia violacea was repeatedly mentioned as the plant species used for the treatment of high blood pressure and predisposing factors in the study area. The brine shrimp cytotoxicity test revealed that fresh, dried methanolic extracts and essential oil of the T. violacea exhibited a high degree of cytotoxic activity with IC50 values of 18.18 (fresh) and 19.24 (dried) μg/ml. An IC50 value of 12. 59 μg/ml was obtained for the essential oil of the plant. The low cytotoxicity values obtained, suggested that rhizome of T. violacea may serve as a potential source of antimicrobial and anticancer agents. In vivo acute study of single oral administration of 5g/kg dose does not produce mortality or significant behavioral changes during 14 days observation. In the sub-chronic study, the extract (250, 500 mg/kg/bwt/ day) administered for a period of 28 days showed no mortality or morbidity. The weekly body and organ weight of the rats showed no significant differences between the control and the rats treated with the extract. The extract at all doses does not show any effect on of biomarkers of liver or renal damage. However, a significant decrease in the activity of ƔGT was observed in the extract treated groups. Hematological evaluation revealed that oral administration of fresh methanolic extracts of rhizomes of T. violacea does not cause anaemia or leucocytosis in the animals. Furthermore, histopathology results of the internal organs revealed no detectable inflammation. These results demonstrated that the rhizome extract of T. violacea was potentially safe for consumption orally even in chronic concentration. In vitro antioxidant evaluation showed that the essential oil, fresh and dried methanolic extracts exhibited potent antioxidant activities in a concentration dependent manner. Phytochemical investigation reveals that the fresh and the dry extract of RTV are rich in flavonoid, flavonol, phenols, tannin and proanthocyanidin, while the essential oil contained dimethy disulfide, dimethyl trisulfide, (methyl methylthio) methyl, 2,4-dithiapentane (11.35 percent) and (methylthio) acetic acid, 2- (methylthio) ethanol, 3-(methylthio) - and propanenitrile (7.20 percent). The fresh extract had higher radicals scavenging activity than the essential oil or dried extract, with 50 percentage inhibition of DPPH, hydrogen peroxide and lipid peroxidation at a concentration of 35.0 ± 0.12, 19.3 ± 0.11 and 17.9 ± 0.15 μg/ml respectively. Oral administration of methanolic extract of RTV in 125, 250 and 500 mg/kg to female Wistar rats significantly inhibited reduction of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). The extracts also inhibited (p< 0.05) lipid peroxidation in normal, high cholesterol and diet induced atherosclerosis fed rats in a dose dependant manner. Also the extract (250 and 500 mg/kg/bwt/day) caused a significant (p<0.05) improvement in body weight of treated animals compared with untreated hypercholesterolemia control rats. The extracts also protected significantly (p<0.05) against atherogenic diet induced liver damage or fatty streaks formation in the aorta as revealed by histological examination. The anti-cholesterolemia and anti-atherosclerotic activities of the extract compared favorably well with standard drugs Gemfibrozil and Atorvastatin respectively. Conclusively, rhizomes of T. violacea possess significant anti-atherogenic activity and its mechanism of action(s) may be due to its antioxidant and anti-hypercholesterolemia properties. The results of this study also suggested that rhizome of T. violacea is relatively safe for human consumption and it may be used as an alternative to garlic.
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- Date Issued: 2012
A bioinorganic investigation of some metal complexes of the Schiff base, N,N'-bis(3-methoxysalicylaldimine)propan-2-ol
- Authors: Mopp, Estelle
- Date: 2010 , 2012-04-13
- Subjects: Schiff bases , Bioinorganic chemistry , Metal complexes , Transition metal complexes , Transition metals , Cancer -- Chemotherapy , Ligands -- Toxicity , Antineoplastic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4413 , http://hdl.handle.net/10962/d1006768 , Schiff bases , Bioinorganic chemistry , Metal complexes , Transition metal complexes , Transition metals , Cancer -- Chemotherapy , Ligands -- Toxicity , Antineoplastic agents
- Description: This thesis includes the synthesis, characterisation, antioxidant and antimicrobial activities of Cu(II)-, Co(II)- and Co(III) complexes with N,N'-bis(3- methoxysalicylaldimine)propan-2-ol, 2-OH-oVANPN. The Schiff base ligand, 2-OHoVANPN, is derived from o-vanillin and 1,3-diaminopropan-2-ol. The o-vanillin condensed with 1,3-diaminopropan-2-ol in a 2:1 molar ratio yields this potential tetraor pentadentate ligand. The complexes synthesized are tetra (or penta or hexa) coordinated. Formation of the complexes is symbolized as follows:- MX₂ + 2-OH-oVANPN (2:1) -> [M(2-OH-oVANPN)Xn] + HnX MX₂ + 2-OH-oVANPN (2:1) -> [Mn(2-OH-oVANPN)OH] + H₂X₂ MX₂ + (o-vanillin : diaminopropanol) (1:1) -> [M(1:1)X₂] MX₂ + (o-vanillin : diaminopropanol) (1:1) -> [M₃(1:1)X₄] M = Cu(II), Co(II) or Co(III); X = Cl; n = 1, 2. Their structural features have been deduced from their elemental analytical data, IR spectral data, and electronic spectral data. With the exception of {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆}(A4), the Cu(II) complexes were monomeric with 2-OH-oVANPN acting as a tetradentate ligand. A binuclear Co(II) complex, [Co₂(C₁₉H₁₉N₂O₅)(OH)] (B1), was synthesised and the rest of the Co(II) and Co(III) complexes were monomeric with chloride ions coordinating to the metal centre in some cases. Electronic data suggest that the cobalt(II) complexes have octahedral geometries and the copper(II) complexes have square planar structures – Co(III) is likely to be octahedral. Thermal analyses, which included the copper-block-method for determining sublimation temperatures, revealed that some copper(II) and cobalt(II) complexes are hygroscopic and sublime at 200 °C and below. DSC analyses of the Cu(II) complexes gave exotherms around 300 °C for complexes K[Cu(C₁₉H₂₀N₂O₅)(OH)]·2H₂O (A1) and [Cu(C₁₁H15N₂O₃)(Cl)₂]·2H₂O (A2) and above 400 °C for [Cu(C₁₁H₁₆N₂O₃)(Cl)₂] (A3) and {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆} (A4). Antioxidant studies were carried out against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·). The cobalt(II) complex, [Co₂(C₁₉H₁₉N₂O₅)(OH)] (B1), which was synthesized in the presence of KOH, had no antioxidant activity, whilst the other cobalt(II) complexes, [Co(C₁₇H₁₇N₂O₅(Cl))]·1½H₂O (B2), [Co(C₁₉H₂₂N₂O₅) (Cl)₂]·5½H₂O (B3) and [Co(C₁₉H₂₂N₂O₅)(Cl)₂]·5½H₂O (B4), which were synthesised in the absence of KOH, demonstrated antioxidant activity. The latter complexes are candidates for cancer cell line testing, while [Cu(C₁₁H₁₆N₂O₃)(Cl)₂] (A3), {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆} (A4), [Co(C₁₉H₂₁N₂O₅)(Cl)₂ ]·5H₂O (C2) and [Co(C₁₉H₂₀N₂O₅)(Cl)]·3H₂O (C3) may show anticancer activity through possible hydrolysis products. Most of the complexes synthesized displayed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans. The results indicated that complexes [Cu(C₁₁H₁₆N₂O₃)(Cl)₂](A3), [Co(C₁₉H₂₂N₂O₅)(Cl)₂]·5½H₂O (B3) and [Co(C₁₉H₂₁N₂O₅)(Cl)₂ ]·5H₂O (C2) are active against the Gram-negative Ps. aeruginosa and that the ligand, 2-OH-oVANPN, did not have any activity. The same trend was observed with 2-OH-oVANPN, {Cu₃(C₁₁H₁₄N₂O₃)(Cl)4(H₂O)₆} (A4) and [Co(C₁₉H₂₀N₂O₅)(Cl)]·3H₂O (C3) against the Gram-positive S. aureus. As for activity against E. coli and C. albicans, some complexes showed more activity than the ligand. There is an observed trend here that the metal complexes are more active (toxic) than the corresponding ligand, which is in agreement with Tweedy’s chelation theory.
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- Date Issued: 2010
Synthesis of triprenylated toluquinone and toluhydroquinone metabolites from a marine-derived Penicillium fungus
- Authors: Scheepers, Brent Ashley
- Date: 2007
- Subjects: Penicillium , Antineoplastic agents , Marine fungi , Quinone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4373 , http://hdl.handle.net/10962/d1005038 , Penicillium , Antineoplastic agents , Marine fungi , Quinone
- Description: This project forms part of a collaborative effort between the marine natural products chemists at Rhodes University and the medical biochemists at the University of Cape Town’s School of Medicine. Our UCT collaborators tested the cytotoxicity of a group of toluhydroquinones and toluquinones (9-15) against the oesophageal cancer cell line WHCO1 and revealed that the triprenylated toluhydroquinone 11 and it’s oxidised analogue 12 were the most active. This thesis presents an investigation into the role of the polyprenyl side-chain in the cytotoxicity of compound 11 and it’s oxidised analogue 12 by synthesizing and testing the cytotoxicity of simplified analogues of this compound. The synthesis of the two ortho-prenylated toluhydroquinone analogues 5-methyl-2-[(2'E,6'E)-3',7' -dimethyl-2',6'-octadienyl]-1,4-benzenediol (19) and 5-methyl-2-[(2'E,6'E)-3',7',11'-trimethyl-2',6',10'-dodecatrienyl]-1,4-benzenediol (21) and their two ortho-prenylated toluquinone analogues, 5-methyl-2-[(2'E,6'E)-3',7'-dimethyl-2',6'-octadienyl]-2,5-cyclohexadiene-1,4-dione (20) and 5-methyl-2-[(2'E,6'E)-3',7',11'-trimethyl-2',6',10'-dodecatrienyl]-2,5-cyclohexadiene-1,4-dione (22) is described. Our initial attempts to couple geranyl bromide, farnesyl bromide and farnesal to the aromatic precursors m-cresol and 1,4-dimethoxy-2-methylbenzene using directed ortho-prenylation and phenoxide carbon-alkylation were unsuccessful. The four target analogues were eventually synthesized via the initial metal halogen exchange reaction between 1-bromo-2,5-dimethoxy-4-methylbenzene and geranyl bromide/farnesyl bromide using n-BuLi and TMEDA in ditheyl ether at 0 °C to yield 92 and 104 respectively in moderate yield. The demethylation of both compounds preceded smoothly using AgO giving the target analogues 20 and 22 in good yield (approx. 90 %). The reduction of quinones 20 and 22 with sodium dithionite gave 19 and 21 in quantitative yield. The synthesis reported here is the first regioselective synthesis of these compounds. The anti-oesophageal cancer activity of 19-22 and two commercially available non-prenylated analogues 17 and 18 were tested against WHCO1. The conclusion drawn from the anti-oesophageal cancer study was that the polyprenyl side-chain plays a negligable role in the cytotoxicity of compounds such as 11 and 9 against the oesophageal cancer cell line WHCO1.
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- Date Issued: 2007
An investigation of the in vitro anticancer properties of selected platinum compounds
- Authors: Du Plessis-Stoman, Debbie
- Date: 2006
- Subjects: Antineoplastic agents , Platinum compounds , Cancer -- Immunological aspects , Cancer -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10334 , http://hdl.handle.net/10948/498 , http://hdl.handle.net/10948/d1012002 , Antineoplastic agents , Platinum compounds , Cancer -- Immunological aspects , Cancer -- Chemotherapy
- Description: This dissertation mainly deals with some biochemical aspects regarding the efficacy of novel platinum anticancer compounds, as part of a broader study in which both chemistry and biochemistry are involved. Various novel diamine and N-S donor chelate compounds of platinum II and IV have been developed in which factors such as stereochemistry, ligand exchange rate and biocompatibility were considered as additional parameters. In the first order testing, each of these compounds was tested with reference to their “killing” potential by comparing their rate of killing, over a period of 48 hours with those of cisplatin and oxaliplatin. Some 80 compounds were tested in this way. Although only a few could be regarded as equal to or even better than cisplatin and oxaliplatin, the testing of these compounds on cancer cells provided useful knowledge for the further development of novel compounds. Four of the better compounds, namely Y9, Y14, Y16 and Lt16.2 were selected for further studies to obtain more detailed knowledge of their anticancer action, including some flow cytometric studies. In addition to the above, cisplatin resistant cells were produced for each of the three different cell lines tested, namely, HeLa, HT29 and MCF7 cancer cell lines, by intermittent and incremental exposure to cisplatin (all the cell lines tested became resistant to cisplatin). Each of the selected compounds were exposed to the cells in the same manner, in order to attempt the induction of resistance against these compounds in the three cell lines tested (i.e. whether these cells will become resistant to the various compounds). Each of these selected platinum containing compounds were subsequently tested against the “cisplatin resistant” cell lines in order to determine their efficacy against such cells. One such compound could be singled out, since cervical cancer cells (HeLa cells) do not become resistant to it. This behaviour is similar to that of oxaliplatin against cervical cancer and colon cancer (HT29) cells (oxaliplatin is the number one treatment for colon cancer at present). This compound also proved to be more active against cisplatin resistant cell lines. It was found that all the compounds induced apoptosis in the cell lines tested as well as inhibit the DNA cycle at one or more phase. Finally, an effort was made to evaluate the different compounds by comparing them with respect to their properties relating to anticancer action.
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- Date Issued: 2006