The elucidation of nickel and zinc based Metal Organic Frameworks (MOFs) using a polycarboxylate-benzene ligand: a synthetic, spectroscopic, and thermoanalytical study
- Authors: Hodgson, Ivan Mark
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/290877 , vital:56795
- Description: Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Hodgson, Ivan Mark
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/290877 , vital:56795
- Description: Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
Structure and interaction studies of beta-amyloid in the search for new lead compounds for the treatment of Alzheimer’s disease
- Authors: Mtini, Onke
- Date: 2020
- Subjects: Alzheimer's disease -- Chemotherapy , Alzheimer's disease -- Treatment , Amyloid beta-protein , Oxidative stress , Protein binding , South African Natural Compounds Database
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167574 , vital:41493
- Description: Alzheimer’s disease (AD) is the most devastating neurodegenerative disorder that effects the aging population worldwide. In this study three hypotheses of AD are explored, the β-amyloid cascade hypothesis, the β-amyloid metal binding hypothesis and the oxidative stress hypothesis are explored. In the first case compounds from the South African Natural Compounds Database (SANCDB) are docked to models of β-amyloid fibrils and the properties of these fibrils under pulling simulations are compared to a known small molecule disruptor of β-amyloid, wgx-50. In these simulations SANCDB compounds are identified that disrupt β-amyloid in a similar manner to wgx-50. In these simulations the disruption to the free energy of binding of chains to the fibrils is quantified. For metal binding and oxidative stress hypotheses, problems in simulation arise due to only fragments of β-amyloid being present in the Research Collaboratory for Structural Bioinformatics protein data bank (RCSB PDB), as determined from NMR experiments. In this work, β-amyloid is set up under periodic boundary conditions to simulate a fibril under reasonable computational time. Within these periodic boundary conditions, β-amyloid has been solvated in copper and zinc rich environments and diffusion of these metals around the fibrils has been explored. The localization of these metals (in simulation only using van der Waal’s and electrostatic terms) around the fibril has led us to explore other possible metal binding sites. Metal bound to the infinite fibril has been optimized at the QM/MM level and some of the reactive oxygen species in the presence of the fibril are quantified.
- Full Text:
- Date Issued: 2020
- Authors: Mtini, Onke
- Date: 2020
- Subjects: Alzheimer's disease -- Chemotherapy , Alzheimer's disease -- Treatment , Amyloid beta-protein , Oxidative stress , Protein binding , South African Natural Compounds Database
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167574 , vital:41493
- Description: Alzheimer’s disease (AD) is the most devastating neurodegenerative disorder that effects the aging population worldwide. In this study three hypotheses of AD are explored, the β-amyloid cascade hypothesis, the β-amyloid metal binding hypothesis and the oxidative stress hypothesis are explored. In the first case compounds from the South African Natural Compounds Database (SANCDB) are docked to models of β-amyloid fibrils and the properties of these fibrils under pulling simulations are compared to a known small molecule disruptor of β-amyloid, wgx-50. In these simulations SANCDB compounds are identified that disrupt β-amyloid in a similar manner to wgx-50. In these simulations the disruption to the free energy of binding of chains to the fibrils is quantified. For metal binding and oxidative stress hypotheses, problems in simulation arise due to only fragments of β-amyloid being present in the Research Collaboratory for Structural Bioinformatics protein data bank (RCSB PDB), as determined from NMR experiments. In this work, β-amyloid is set up under periodic boundary conditions to simulate a fibril under reasonable computational time. Within these periodic boundary conditions, β-amyloid has been solvated in copper and zinc rich environments and diffusion of these metals around the fibrils has been explored. The localization of these metals (in simulation only using van der Waal’s and electrostatic terms) around the fibril has led us to explore other possible metal binding sites. Metal bound to the infinite fibril has been optimized at the QM/MM level and some of the reactive oxygen species in the presence of the fibril are quantified.
- Full Text:
- Date Issued: 2020
Molecular simulations of potential agents and targets of Alzheimer’s disease
- Authors: Carlisle, Tanya
- Date: 2020
- Subjects: Alzheimer's disease -- Treatment , Alzheimer's disease -- Molecular aspects , Amyloid beta-protein precurs , Amyloid beta-protein
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140025 , vital:37825
- Description: The World Alzheimer Report statedin 2016 that approximately 46.8 million people were living with dementia and this figure is expected to triple by 2050. Alzheimer’s Disease was discovered to be a precursor to dementia in 1976 and since then efforts to understand Alzheimer’s have been prioritized. To date, there are very few effective forms of treatment for Alzheimer’s, many are known to offer only mild calming of the symptoms and have side effects such as diarrhea, nausea, loss of appetite and sleep disturbances. This has been due to lack of understanding on how Alzheimer’s is caused. With the two main hallmarks of the disease now being more understood it has opened the doorway into the discovery of new treatments for this disease. This study focuses on the hallmark involving the aggregation of the β-amyloid protein to form plaques surrounding the neurons of the brain. Copper, Zinc and Iron have also been found in high concentrations in and surrounding these plaques. This study focused on the screening of the South African Natural Compound database (SANCDB) to discover hits that have potential destabilizing action against the Beta-amyloid aggregate. If one of these compounds could prove to have destabilizing action on the aggregate it could open the doorway to new potential forms of treatment. Over 700 SANCDB compounds were docked, and the top hits were taken to molecular dynamics to further study the interactions of the compounds and the aggregate. However, the hits identified had strong binding to the aggregate causing it to become stable instead of the desired effect of destabilizing the structure. This information, however, does not rule out the possibility of these compounds preventing the formation of the aggregates. Further, interactions of copper with β-amyloid and copper were determined by solubilizing the aggregate and introducing copper ions in a dynamics simulation. Possible interactions between copper and the methionine residues were visualised.
- Full Text:
- Date Issued: 2020
- Authors: Carlisle, Tanya
- Date: 2020
- Subjects: Alzheimer's disease -- Treatment , Alzheimer's disease -- Molecular aspects , Amyloid beta-protein precurs , Amyloid beta-protein
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/140025 , vital:37825
- Description: The World Alzheimer Report statedin 2016 that approximately 46.8 million people were living with dementia and this figure is expected to triple by 2050. Alzheimer’s Disease was discovered to be a precursor to dementia in 1976 and since then efforts to understand Alzheimer’s have been prioritized. To date, there are very few effective forms of treatment for Alzheimer’s, many are known to offer only mild calming of the symptoms and have side effects such as diarrhea, nausea, loss of appetite and sleep disturbances. This has been due to lack of understanding on how Alzheimer’s is caused. With the two main hallmarks of the disease now being more understood it has opened the doorway into the discovery of new treatments for this disease. This study focuses on the hallmark involving the aggregation of the β-amyloid protein to form plaques surrounding the neurons of the brain. Copper, Zinc and Iron have also been found in high concentrations in and surrounding these plaques. This study focused on the screening of the South African Natural Compound database (SANCDB) to discover hits that have potential destabilizing action against the Beta-amyloid aggregate. If one of these compounds could prove to have destabilizing action on the aggregate it could open the doorway to new potential forms of treatment. Over 700 SANCDB compounds were docked, and the top hits were taken to molecular dynamics to further study the interactions of the compounds and the aggregate. However, the hits identified had strong binding to the aggregate causing it to become stable instead of the desired effect of destabilizing the structure. This information, however, does not rule out the possibility of these compounds preventing the formation of the aggregates. Further, interactions of copper with β-amyloid and copper were determined by solubilizing the aggregate and introducing copper ions in a dynamics simulation. Possible interactions between copper and the methionine residues were visualised.
- Full Text:
- Date Issued: 2020
Molecular simulations of potential agents and targets of Alzheimer’s disease
- Authors: Joli, Luxolo
- Date: 2020
- Subjects: Alzheimer's disease -- Chemotherapy , Alzheimer's disease -- Treatment , Ligands (Biochemistry) , Proteins -- Chemistry , Molecular dynamics -- Simulation methods
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146411 , vital:38523
- Description: Alzheimer's Disease (AD) is a neurodegenerative brain disorder that was first discovered in 1901 by Dr Aloïs Alzheimer and was later reported publicly in 1906. The German doctor had a 51-yearold woman patient called Auguste Deter, who was suffering from a rare brain disorder with early signs of memory loss and cognition. Alzheimer's Disease is the most common type of dementia that affects people with the age of 65 years and older. There is no single known cause of Alzheimer’s disease however, amyloid β-peptide (Aβ1–40/42) was found to be at the centre of AD pathogenesis and this connection was referred as “amyloid hypothesis”. It is suspected that an accumulation of amyloid β-peptide is a major contributor to neuronal dysfunction and degeneration. Alzheimer’s disease is complex and therefore, currently there is no medication available that treats the disease. However, there are approaches that focus on helping people maintain mental function, manage behavioral symptoms, and slow down the symptoms of disease. According to South Africa’s 2011 census, there are approximately 2.2 million people in South Africa with some form of dementia and therefore there is a need to find a treatment for the disease. This study aims to find agents and targets of Alzheimer’s Disease by using different computational techniques such as molecular modelling. The study will use compounds from the South African Compounds Database (SANCDB) and the following therapeutic targets α-, β- and γ-secretase, acetylcholinesterase, tau protein and neprilysin. A successful High-throughput Virtual Screening (HTVS) study to determine lead compounds was performed using a computational program called KNIME. Molecular docking was achieved with GLIDE as it allows for exhaustive ligand flexibility. The docking calculations were carried out using the high level of precision XP (extra precision) for enhanced docking accuracy. The binding affinities (docking scores) for the best bound ligands obtained from docking were in the order of -5 kcal/mol or less. The ligandSANC00370 was the best binding ligand against the protein 1J1C_B and had the best binding energy of -13.94 kcal/mol compared to others. The receptor-ligand complexes were analyzed using the interaction diagrams obtained from the Discovery Studio Visualizer and Maestro programs. Molecular Dynamics simulations were performed on the complexes obtained from docking to help in optimizing their interactions. The simulations were performed using the Desmond tool with the OPLS3 force field. 100 ns simulations were performed for six systems with the best docking score results epresenting each of the therapeutic targets and for the other complex systems, 50 ns simulations were performed. The Desmond simulations were analyzed using the Simulations Interaction Diagrams such as PL-RMSD, L-RMSF, P-RMSF, L-Torsions, P-SSE, LP-Contacts and L-Properties. Maestro was used to visualize the stability of the ligands in the active site during the simulation. All 13 Desmond simulations were successful however, there were 9 simulations which produced satisfactory results while the others were nsatisfactory. Based on the molecular docking and Molecular Dynamics results of this study, 9 potential targets and 6 potential agents were obtained successfully and can be studied further as therapeutics for Alzheimer’s Disease.
- Full Text:
- Date Issued: 2020
- Authors: Joli, Luxolo
- Date: 2020
- Subjects: Alzheimer's disease -- Chemotherapy , Alzheimer's disease -- Treatment , Ligands (Biochemistry) , Proteins -- Chemistry , Molecular dynamics -- Simulation methods
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/146411 , vital:38523
- Description: Alzheimer's Disease (AD) is a neurodegenerative brain disorder that was first discovered in 1901 by Dr Aloïs Alzheimer and was later reported publicly in 1906. The German doctor had a 51-yearold woman patient called Auguste Deter, who was suffering from a rare brain disorder with early signs of memory loss and cognition. Alzheimer's Disease is the most common type of dementia that affects people with the age of 65 years and older. There is no single known cause of Alzheimer’s disease however, amyloid β-peptide (Aβ1–40/42) was found to be at the centre of AD pathogenesis and this connection was referred as “amyloid hypothesis”. It is suspected that an accumulation of amyloid β-peptide is a major contributor to neuronal dysfunction and degeneration. Alzheimer’s disease is complex and therefore, currently there is no medication available that treats the disease. However, there are approaches that focus on helping people maintain mental function, manage behavioral symptoms, and slow down the symptoms of disease. According to South Africa’s 2011 census, there are approximately 2.2 million people in South Africa with some form of dementia and therefore there is a need to find a treatment for the disease. This study aims to find agents and targets of Alzheimer’s Disease by using different computational techniques such as molecular modelling. The study will use compounds from the South African Compounds Database (SANCDB) and the following therapeutic targets α-, β- and γ-secretase, acetylcholinesterase, tau protein and neprilysin. A successful High-throughput Virtual Screening (HTVS) study to determine lead compounds was performed using a computational program called KNIME. Molecular docking was achieved with GLIDE as it allows for exhaustive ligand flexibility. The docking calculations were carried out using the high level of precision XP (extra precision) for enhanced docking accuracy. The binding affinities (docking scores) for the best bound ligands obtained from docking were in the order of -5 kcal/mol or less. The ligandSANC00370 was the best binding ligand against the protein 1J1C_B and had the best binding energy of -13.94 kcal/mol compared to others. The receptor-ligand complexes were analyzed using the interaction diagrams obtained from the Discovery Studio Visualizer and Maestro programs. Molecular Dynamics simulations were performed on the complexes obtained from docking to help in optimizing their interactions. The simulations were performed using the Desmond tool with the OPLS3 force field. 100 ns simulations were performed for six systems with the best docking score results epresenting each of the therapeutic targets and for the other complex systems, 50 ns simulations were performed. The Desmond simulations were analyzed using the Simulations Interaction Diagrams such as PL-RMSD, L-RMSF, P-RMSF, L-Torsions, P-SSE, LP-Contacts and L-Properties. Maestro was used to visualize the stability of the ligands in the active site during the simulation. All 13 Desmond simulations were successful however, there were 9 simulations which produced satisfactory results while the others were nsatisfactory. Based on the molecular docking and Molecular Dynamics results of this study, 9 potential targets and 6 potential agents were obtained successfully and can be studied further as therapeutics for Alzheimer’s Disease.
- Full Text:
- Date Issued: 2020
Benzoyl isothiocyanates derived ligands as potential HIV-1 protease inhibitors and their reactions with gold ions
- Authors: Odame, Felix
- Date: 2016
- Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/33228 , vital:32585
- Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
- Full Text:
- Date Issued: 2016
- Authors: Odame, Felix
- Date: 2016
- Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/33228 , vital:32585
- Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
- Full Text:
- Date Issued: 2016
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