Isolation, structural characterisation and evaluation of cytotoxic activity of natural products from selected South African marine red algae
- Authors: Knott, Michael George
- Date: 2012
- Subjects: Marine algae -- South Africa , Red algae -- South Africa , Pharmaceutical chemistry
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3862 , http://hdl.handle.net/10962/d1015460
- Description: The medicinal chemistry of selected marine algae indigenous to South Africa was investigated. Following the isolation and characterisation of a number of new and known compounds, the associated in vitro cytotoxic profiles of these new compounds was investigated. Plocamium maxillosum yielded two new cyclic polyhalogenated monoterpenes which were characterised as 2E-chloromethine-4E-chlorovinyl-4-methyl-5-cyclohexen-1-one (2.1) and 2Z-chloromethine-4E-chlorovinyl-4-methyl-5-cyclohexen-1-one (2.2) on the basis of one and two dimensional NMR spectroscopic data and MS analysis. These compounds were also found to have good cytotoxic activity against breast cancer cell lines. Although these compounds are based on a regular monoterpene skeleton, they represent an uncommon feature not often seen in cyclic halogenated monoterpenes from marine algae. Plocamium robertiae yielded one new cyclic polyhalogenated monoterpene identified as 4,5- dibromo-5-chloromethyl-1-chlorovinyl-2-chloro-methylcyclohexane (2.6) and one known compound called 2,4-dichloro-1-chlorovinyl-1-methylcyclohexane-5-ene or Plocamene D (2.9). Portieria hornemannii was collected from Port Edward in Natal and yielded three new compounds, namely; 3Z-1,6-dibromo-3-(bromomethylidene)-2,7-dichloro-7-methyloctane (3.1), 1E,3Z-1,6-dibromo-3-(bromomethylidene)-7-chloro-7-methyloct-1-ene (3.2), 1Z,3Z- 1,6-dibromo-3-(bromomethylidene)-7-chloro-7-methyloct-1-ene (3.3), and one known compound, namely; 3S,6R-6-bromo-3-(bromomethyl)-3,7-dichloro-7-methyloct-1-ene (3.4). Compounds 3.1 and 3.2 showed no cytotoxic activity against breast cancer cells. Another Portieria hornemannii sample was collected from Noordhoek in the Eastern Cape, it yielded one known compound referred to as 3Z-6-bromo-3-(bromomethylidene)-2,7- dichloro-7-methyloct-1-ene (3.5), as well as one new compound called portieric acid A (3.6) or 5-bromo-2-(bromomethylidene)-6-chloro-6-methylheptanoic acid. Portieric acid A showed slight cytotoxic activity and also represents a new class of compound within the genus Portieria. The isolation of secondary metabolites from the South African red alga, Laurencia glomerata, yielded two known compounds; 7-hydroxylaurene (4.9) and cis-neolaurencenyne (4.12), as well as one chamigrane related compound (4.11). Laurencia flexuosa yielded one known compound called 3Z-bromofucin (4.13). Using 1H NMR, GC and molecular systematics, a novel method for identifying different species of Laurencia was also investigated.
- Full Text:
- Date Issued: 2012
- Authors: Knott, Michael George
- Date: 2012
- Subjects: Marine algae -- South Africa , Red algae -- South Africa , Pharmaceutical chemistry
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3862 , http://hdl.handle.net/10962/d1015460
- Description: The medicinal chemistry of selected marine algae indigenous to South Africa was investigated. Following the isolation and characterisation of a number of new and known compounds, the associated in vitro cytotoxic profiles of these new compounds was investigated. Plocamium maxillosum yielded two new cyclic polyhalogenated monoterpenes which were characterised as 2E-chloromethine-4E-chlorovinyl-4-methyl-5-cyclohexen-1-one (2.1) and 2Z-chloromethine-4E-chlorovinyl-4-methyl-5-cyclohexen-1-one (2.2) on the basis of one and two dimensional NMR spectroscopic data and MS analysis. These compounds were also found to have good cytotoxic activity against breast cancer cell lines. Although these compounds are based on a regular monoterpene skeleton, they represent an uncommon feature not often seen in cyclic halogenated monoterpenes from marine algae. Plocamium robertiae yielded one new cyclic polyhalogenated monoterpene identified as 4,5- dibromo-5-chloromethyl-1-chlorovinyl-2-chloro-methylcyclohexane (2.6) and one known compound called 2,4-dichloro-1-chlorovinyl-1-methylcyclohexane-5-ene or Plocamene D (2.9). Portieria hornemannii was collected from Port Edward in Natal and yielded three new compounds, namely; 3Z-1,6-dibromo-3-(bromomethylidene)-2,7-dichloro-7-methyloctane (3.1), 1E,3Z-1,6-dibromo-3-(bromomethylidene)-7-chloro-7-methyloct-1-ene (3.2), 1Z,3Z- 1,6-dibromo-3-(bromomethylidene)-7-chloro-7-methyloct-1-ene (3.3), and one known compound, namely; 3S,6R-6-bromo-3-(bromomethyl)-3,7-dichloro-7-methyloct-1-ene (3.4). Compounds 3.1 and 3.2 showed no cytotoxic activity against breast cancer cells. Another Portieria hornemannii sample was collected from Noordhoek in the Eastern Cape, it yielded one known compound referred to as 3Z-6-bromo-3-(bromomethylidene)-2,7- dichloro-7-methyloct-1-ene (3.5), as well as one new compound called portieric acid A (3.6) or 5-bromo-2-(bromomethylidene)-6-chloro-6-methylheptanoic acid. Portieric acid A showed slight cytotoxic activity and also represents a new class of compound within the genus Portieria. The isolation of secondary metabolites from the South African red alga, Laurencia glomerata, yielded two known compounds; 7-hydroxylaurene (4.9) and cis-neolaurencenyne (4.12), as well as one chamigrane related compound (4.11). Laurencia flexuosa yielded one known compound called 3Z-bromofucin (4.13). Using 1H NMR, GC and molecular systematics, a novel method for identifying different species of Laurencia was also investigated.
- Full Text:
- Date Issued: 2012
The medicinal chemistry of Cyclo (D-PHE-4I-PRO) and Cyclo (L-PHE-4I-PRO)
- Authors: Qhola, Lipolelo
- Date: 2012
- Subjects: Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10152 , http://hdl.handle.net/10948/d1011619 , Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Description: Cyclic dipeptides have been widely used as pharmaceutical agents due to their favourable properties and the fact that they are more stable and membrane permeable than their linear analogues. These characteristics make cyclic dipeptides attractive to protein-based drug developers (Martins & Carvalho, 2007). In this research study, the method of Milne et al. (1992) was used to synthesize the protected linear dipeptide esters. This was followed by boiling the unprotected, linear dipeptide esters under reflux in an oil bath (Sec-butanol: toluene (4:1)). This method gave good yields and pure cyclic dipeptides. Scanning electron microscopy, thermal analysis, X-ray powder diffraction and differential scanning calorimetry were used for evaluation of the physiochemical properties of the cyclic dipeptides. High-performance liquid chromatography and thin layer chromatography were used to determine the purity of the cyclic dipeptides. The structures of the cyclic dipeptides were elucidated using infrared spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy and molecular modeling and computational chemistry. The aim of the study was to determine the possible therapeutic activity of cyclo(D-Phe-4I-Pro) and cyclo(L-Phe-4I-Pro) with regard to antimicrobial, anticancer, antidiabetes and haematological effects. Both cyclic dipeptides showed a significant growth inhibition of Gram-positive, Gram-negative and fungal microorganisms in the antimicrobial study. Anticancer studies showed that both cyclic dipeptides caused growth inhibition of the MCF-7, HT-29 and HeLa cancer cell lines. Both cyclic dipeptides showed no antidiabetic activity. Haematological studies revealed that both cyclic dipeptides caused a significant effect on the clotting time and platelet aggregation. They caused an increase in clotting time and also inhibited platelet aggregation.
- Full Text:
- Date Issued: 2012
- Authors: Qhola, Lipolelo
- Date: 2012
- Subjects: Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10152 , http://hdl.handle.net/10948/d1011619 , Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Description: Cyclic dipeptides have been widely used as pharmaceutical agents due to their favourable properties and the fact that they are more stable and membrane permeable than their linear analogues. These characteristics make cyclic dipeptides attractive to protein-based drug developers (Martins & Carvalho, 2007). In this research study, the method of Milne et al. (1992) was used to synthesize the protected linear dipeptide esters. This was followed by boiling the unprotected, linear dipeptide esters under reflux in an oil bath (Sec-butanol: toluene (4:1)). This method gave good yields and pure cyclic dipeptides. Scanning electron microscopy, thermal analysis, X-ray powder diffraction and differential scanning calorimetry were used for evaluation of the physiochemical properties of the cyclic dipeptides. High-performance liquid chromatography and thin layer chromatography were used to determine the purity of the cyclic dipeptides. The structures of the cyclic dipeptides were elucidated using infrared spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy and molecular modeling and computational chemistry. The aim of the study was to determine the possible therapeutic activity of cyclo(D-Phe-4I-Pro) and cyclo(L-Phe-4I-Pro) with regard to antimicrobial, anticancer, antidiabetes and haematological effects. Both cyclic dipeptides showed a significant growth inhibition of Gram-positive, Gram-negative and fungal microorganisms in the antimicrobial study. Anticancer studies showed that both cyclic dipeptides caused growth inhibition of the MCF-7, HT-29 and HeLa cancer cell lines. Both cyclic dipeptides showed no antidiabetic activity. Haematological studies revealed that both cyclic dipeptides caused a significant effect on the clotting time and platelet aggregation. They caused an increase in clotting time and also inhibited platelet aggregation.
- Full Text:
- Date Issued: 2012
The medicinal chemistry of cyclo(Phe-4CI-Pro) and Cyclo(D-Phe-4CI-Pro)
- Authors: Milne, Marnus
- Date: 2012
- Subjects: Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10157 , http://hdl.handle.net/10948/d1011848 , Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Description: Cyclic dipeptides have limited conformational freedom due to their diketopiperazine backbone and their small size. They are relatively simple to synthesise, making them ideal subjects for investigation into their biological effects. Cyclic dipeptides have also been known for their multitude of biological activities, including antimicrobial, anticancer and haematological properties. In this study the cyclic dipeptides, cyclo(Phe-4Cl-Pro) and cyclo(D-Phe-4Cl-Pro), were synthesised from their corresponding linear precursors using a modified phenol-induced cyclisation procedure. The phenol induced cyclisation procedure resulted in good yields and purity of the cyclic dipeptides. Quantitative analysis and evaluation of the physiochemical properties of the cyclic dipeptides was achieved using high-performance liquid chromatography, scanning electron microscopy, thermal analysis and X-ray powder diffraction. Structural elucidation of the cyclic dipeptides was done by means of infrared spectroscopy, mass spectroscopy, nuclear magnetic resonance spectroscopy and molecular modelling. The study‟s aim was to determine the biological activity of cyclo(Phe-4Cl-Pro) and cyclo(D-Phe-4Cl-Pro) with respect to their anticancer, antimicrobial, haematological and ant-diabetic studies. Anticancer studies revealed that cyclo(Phe-4Cl-Pro) and cyclo(D-Phe-4Cl-Pro) inhibited the growth of HeLa (cervical cancer), HT-29 (colon cancer) and MCF-7 (breast cancer) cancer cell lines. Both cyclic dipeptides also inhibited the growth of certain selected Gram-positive, Gram-negative and fungal microorganisms in the antimicrobial study. Although the inhibition of growth in the anticancer and antimicrobial studies was statistically significant, the clinical relevance is questionable, since the inhibition produced by both cyclic dipeptides was very limited compared to other pre-existing anticancer and antimicrobial agents. Both cyclic dipeptides caused a significant shortening of the APTT and PT clotting times and an increase in the fibrin and D-Dimer formation. Cyclo(D-Phe-4Cl-Pro) at a screening concentration of 12.5 mM and 3.125 mM, showed significant anti-platelet activity. Both cyclic dipeptides failed to produce any inhibition of the α-Glucosidase enzyme and very limited inhibition of the α-Amylase enzyme.
- Full Text:
- Date Issued: 2012
- Authors: Milne, Marnus
- Date: 2012
- Subjects: Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10157 , http://hdl.handle.net/10948/d1011848 , Cyclic peptides , Pharmaceutical chemistry , Peptide drugs
- Description: Cyclic dipeptides have limited conformational freedom due to their diketopiperazine backbone and their small size. They are relatively simple to synthesise, making them ideal subjects for investigation into their biological effects. Cyclic dipeptides have also been known for their multitude of biological activities, including antimicrobial, anticancer and haematological properties. In this study the cyclic dipeptides, cyclo(Phe-4Cl-Pro) and cyclo(D-Phe-4Cl-Pro), were synthesised from their corresponding linear precursors using a modified phenol-induced cyclisation procedure. The phenol induced cyclisation procedure resulted in good yields and purity of the cyclic dipeptides. Quantitative analysis and evaluation of the physiochemical properties of the cyclic dipeptides was achieved using high-performance liquid chromatography, scanning electron microscopy, thermal analysis and X-ray powder diffraction. Structural elucidation of the cyclic dipeptides was done by means of infrared spectroscopy, mass spectroscopy, nuclear magnetic resonance spectroscopy and molecular modelling. The study‟s aim was to determine the biological activity of cyclo(Phe-4Cl-Pro) and cyclo(D-Phe-4Cl-Pro) with respect to their anticancer, antimicrobial, haematological and ant-diabetic studies. Anticancer studies revealed that cyclo(Phe-4Cl-Pro) and cyclo(D-Phe-4Cl-Pro) inhibited the growth of HeLa (cervical cancer), HT-29 (colon cancer) and MCF-7 (breast cancer) cancer cell lines. Both cyclic dipeptides also inhibited the growth of certain selected Gram-positive, Gram-negative and fungal microorganisms in the antimicrobial study. Although the inhibition of growth in the anticancer and antimicrobial studies was statistically significant, the clinical relevance is questionable, since the inhibition produced by both cyclic dipeptides was very limited compared to other pre-existing anticancer and antimicrobial agents. Both cyclic dipeptides caused a significant shortening of the APTT and PT clotting times and an increase in the fibrin and D-Dimer formation. Cyclo(D-Phe-4Cl-Pro) at a screening concentration of 12.5 mM and 3.125 mM, showed significant anti-platelet activity. Both cyclic dipeptides failed to produce any inhibition of the α-Glucosidase enzyme and very limited inhibition of the α-Amylase enzyme.
- Full Text:
- Date Issued: 2012
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