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.
- Full Text:
- Date Issued: 2010
- 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.
- Full Text:
- Date Issued: 2010
A combination of platinum anticancer drugs and mangiferin causes increased efficacy in cancer cell lines
- Authors: Du Plessis-Stoman, Debbie
- Date: 2010
- Subjects: Cancer -- Chemotherapy , Antineoplastic agents , Platinum compounds -- Therapeutic use , Cancer cells
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10338 , http://hdl.handle.net/10948/d1016160
- Description: This thesis mainly deals with some biochemical aspects regarding the efficacy of novel platinum anticancer compounds alone and in combination with mangiferin, 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. Numerous novel compounds were tested in this way, using the MTT cell viability assay and the three cancer cell lines MCF7, HT29 and HeLa. Although only a few could be regarded as equal to or even better than cisplatin, CPA7 and oxaliplatin, the testing of these compounds on cancer cells provided useful knowledge for the further development of novel compounds. Three of the better compounds, namely Yol 25, Yol 29.1 and Mar 4.1.4 were selected for further studies, together with oxaliplatin and CPA7 as positive controls, to obtain more detailed knowledge of their anticancer action, both alone and when applied in combination with mangiferin. In addition to the above, resistant cells were produced for each of the three different cell lines tested and all the selected compounds, both in the presence and absence of mangiferin. The effects of these treatments on the activation of NFĸB when applied to normal and resistant cell lines were also investigated. All the compounds induced apoptosis in the cell lines tested as well as alter the DNA cycle at one or more phase. Additionally, combination of these compounds with mangiferin enhanced the above-mentioned effects. Mangiferin decreases the IC50 values of the platinum drugs by up to 3.4 times and, although mangiferin alone did not induce cell cycle arrest, the presence of mangiferin in combination with oxaliplatin and Yol 25 shows an earlier and greatly enhanced delay in the S-phase, while cells treated with CPA7, Yol 29.1 and Mar 4.1.4 in combination with mangiferin showed a later, but greatly enhanced delay in the S-phase. It was also found that mangiferin acts as an NFĸB inhibitor when applied in combination with these drugs, which, in turn, reduces the occurrence of resistance in the cell lines. Resistance to oxaliplatin was counteracted by the combination with mangiferin in HeLa and HT29, but not in MCF7 cells, while resistance to CPA7 was only counteracted in the MCF7 cell line. Yol 25 and Mar 4.1.4 did not seem to induce resistance in HeLa and MCF7 cells, but did in HT29 cells, whereas Yol 29.1 caused resistance in HeLa and HT29 cells, but not in MCF7 cells. Finally, an effort was made to evaluate the different compounds by comparing them with respect to their properties relating to anticancer action with and without the addition of mangiferin.
- Full Text:
- Date Issued: 2010
- Authors: Du Plessis-Stoman, Debbie
- Date: 2010
- Subjects: Cancer -- Chemotherapy , Antineoplastic agents , Platinum compounds -- Therapeutic use , Cancer cells
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10338 , http://hdl.handle.net/10948/d1016160
- Description: This thesis mainly deals with some biochemical aspects regarding the efficacy of novel platinum anticancer compounds alone and in combination with mangiferin, 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. Numerous novel compounds were tested in this way, using the MTT cell viability assay and the three cancer cell lines MCF7, HT29 and HeLa. Although only a few could be regarded as equal to or even better than cisplatin, CPA7 and oxaliplatin, the testing of these compounds on cancer cells provided useful knowledge for the further development of novel compounds. Three of the better compounds, namely Yol 25, Yol 29.1 and Mar 4.1.4 were selected for further studies, together with oxaliplatin and CPA7 as positive controls, to obtain more detailed knowledge of their anticancer action, both alone and when applied in combination with mangiferin. In addition to the above, resistant cells were produced for each of the three different cell lines tested and all the selected compounds, both in the presence and absence of mangiferin. The effects of these treatments on the activation of NFĸB when applied to normal and resistant cell lines were also investigated. All the compounds induced apoptosis in the cell lines tested as well as alter the DNA cycle at one or more phase. Additionally, combination of these compounds with mangiferin enhanced the above-mentioned effects. Mangiferin decreases the IC50 values of the platinum drugs by up to 3.4 times and, although mangiferin alone did not induce cell cycle arrest, the presence of mangiferin in combination with oxaliplatin and Yol 25 shows an earlier and greatly enhanced delay in the S-phase, while cells treated with CPA7, Yol 29.1 and Mar 4.1.4 in combination with mangiferin showed a later, but greatly enhanced delay in the S-phase. It was also found that mangiferin acts as an NFĸB inhibitor when applied in combination with these drugs, which, in turn, reduces the occurrence of resistance in the cell lines. Resistance to oxaliplatin was counteracted by the combination with mangiferin in HeLa and HT29, but not in MCF7 cells, while resistance to CPA7 was only counteracted in the MCF7 cell line. Yol 25 and Mar 4.1.4 did not seem to induce resistance in HeLa and MCF7 cells, but did in HT29 cells, whereas Yol 29.1 caused resistance in HeLa and HT29 cells, but not in MCF7 cells. Finally, an effort was made to evaluate the different compounds by comparing them with respect to their properties relating to anticancer action with and without the addition of mangiferin.
- Full Text:
- Date Issued: 2010
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.
- Full Text:
- Date Issued: 2006
- 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.
- Full Text:
- Date Issued: 2006
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