Hajierah Davids - Academia.edu (original) (raw)
Papers by Hajierah Davids
Pharmaceutics
Tuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is ne... more Tuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is neglected globally as evidenced by treatment and clinical care schemes, mostly extrapolated from studies in adults. The objective of this study was to formulate and evaluate a reconstitutable dry suspension (RDS) containing isoniazid, a first-line anti-tubercular agent used in the treatment and prevention of TB infection in both children and adults. The RDS formulation was prepared by direct dispersion emulsification of an aqueous-lipid particulate interphase coupled with lyophilization and dry milling. The RDS appeared as a cream-white free-flowing powder with a semi-crystalline and microparticulate nature. Isoniazid release was characterized with an initial burst up to 5 minutes followed by a cumulative release of 67.88% ± 1.88% (pH 1.2), 60.18% ± 3.33% (pH 6.8), and 49.36% ± 2.83% (pH 7.4) over 2 h. An extended release at pH 7.4 and 100% drug liberation was achieved within 300 min. The ...
International Journal of Toxicology
Potential applications of gold nanoparticles in biomedicine have increasingly been reported on ac... more Potential applications of gold nanoparticles in biomedicine have increasingly been reported on account of the ease of synthesis, bioinert characteristics, optical properties, chemical stability, high biocompatibility, and specificity. The safety of these particles remains a great concern, as there are differences among toxicity study protocols used. This article focuses on integrating results of research on the toxicological behavior of gold nanoparticles. This can be influenced by the physicochemical properties, including size, shape, surface charge, and other factors, such as methods used in the synthesis of gold nanoparticles, models used, dose, in vivo route of administration, and interference of gold nanoparticles with in vitro toxicity assay systems. Several researchers have reported toxicological studies with regard to gold nanoparticles, using various in vitro, in vivo, and in ovo models. The conflicting results concerning the toxicity of gold nanoparticles should thus be ad...
Biochemical Pharmacology, 1981
4-hr pretreatment with methotrexate antagonized the cytotoxic effect of subsequent arabinosylcyto... more 4-hr pretreatment with methotrexate antagonized the cytotoxic effect of subsequent arabinosylcytosine treatment in rat hepatoma cells of lines NISI and 3924A, but in the hepatoma line 8999R and the fibroblast line BF5, MTX pretreatment was synergistic with the arabinosylcytosine treatment. Measurement of cellular deoxyribonucleoside triphosphate concentrations showed that in those lines in which antagonism was found the dCTP increased, whereas in the lines where the drugs were synergistic the dCTP pool was decreased. Conversely, dATP levels were high when the drugs were synergistic and low when antagonism was obtained. Although methotrexate pretreatment antagonized arabinosylcytosine in N& and 3924A cells, pretreatment of these cells with the combination of methotrexate plus a purine (either hypoxanthine or 2'-deoxyadenosine) resulted in synergism with arabinosylcytosine. Deoxynucleotide pool measurements showed that methotrexate in combination with either hypoxanthine or 2'-deoxyadenosine increased dATP and decreased dCTP in the NISl and 3924A hepatoma cells. In NtSl cells, pretreatment with 2'-deoxyadenosine alone for 4 hr was synergistic with arabinosylcytosine. It was concluded that elevated dATF' pools enhanced arabinosylcytosine cytotoxicity by depleting the dCTP pool, through feedback inhibition of ribonucleotide reductase, thus causing greater inhibition of DNA biosynthesis and greater incorporation of AraCI? into nucleic acid, Methotrexate was synergistic in those cell lines where dATP accumulated and dCTP was decreased, but when methotrexate had a potent antipurine effect dCTP pools increased and arabinosylcytosine was antagonized. The synergistic interaction was more marked at cytocidal drug concentrations than it wag at growth-inhibitor doses.
Anticancer research, Dec 1, 2017
Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to c... more Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity. Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells. Rau 015 (15 μM) and curcumin (112.5 μM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 μM) and curcumin (100 μM) displayed similar effects in MCF-7 and MG-63 cells. We report on the potential of ...
Bioorganic & medicinal chemistry, Jan 15, 2016
Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthes... more Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentration of 100μM against a small panel of tumor cell lines (HL-60, K-562, Jurkat, Caco-2 and HT-29). The entire set was also tested at varying concentrations against two human glioma lines (U373 and Hs683) to obtain GI50 values, with the best results being values of ∼25μM.
Bioprocess and Biosystems Engineering, Jun 14, 2007
Cassava (Manihot esculenta Crantz) is a known source of linamarin, but difficulties associated wi... more Cassava (Manihot esculenta Crantz) is a known source of linamarin, but difficulties associated with its isolation have prevented it from being exploited as a major source. A batch adsorption process using activated carbon proved successful in its isolation, with ultrafiltration playing a pivotal role in its purification. Thirty-two minutes of contact time was required for 60 g of extract, yielding 1.7 g of purified product. Picrate paper, infra-red and 'HNMR analysis confirmed the presence and structure of linamarin. Cytotoxic effects of linamarin on MCF-7, HT-29 and HL60 cells were determined using the MTT assay. Cytotoxic effects were significantly increased in the presence of linamarase (P-glucosidase), with a 10-fold decrease in the IC50 values obtained for HL-60 cells. This study thus describes a method for the isolation and purification of linamarin from cassava, as well as its cytotoxicity potential.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2010
Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients ... more Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at Johannesburg General Hospital with those of healthy controls (26 adults) from the general population. Heparin levels in the blood samples were tested using the Chromogenix Coatest Heparin kit. The blood of the patients contained significantly lower levels of endogenous heparin compared with that of the healthy individuals, indicating that the anti-inflammatory properties afforded by heparin are absent in these patients.
Tetrahedron, 2007
A number of protected 7-isopropoxy-8-methoxy-1,2,3,6-tetrahydro-2-benzazocines were synthesized f... more A number of protected 7-isopropoxy-8-methoxy-1,2,3,6-tetrahydro-2-benzazocines were synthesized from 2-allyl-3-isopropoxy-4-methoxybenzaldehyde using ring-closing metathesis as the key step. In addition, two 9-isopropoxy-8-methoxy-3,6-dihydro-2-benzazocines were synthesized from 5-isopropoxy-4-methoxy-2-[(1E)-3-phenyl-2-propenyl]benzaldehyde, which in turn was obtained from the thermal Claisen-Cope rearrangement of 4-methoxy-3-{[(2E)-3-phenyl-2-propenyl]oxy}benzaldehyde. Finally, five of the 2-benzazocine compounds were tested for anti-cancer activity.
South African Journal of Botany, 2011
The antimicrobial activity of 35 indigenous South African Helichrysum species was determined agai... more The antimicrobial activity of 35 indigenous South African Helichrysum species was determined against six microorganisms. Seven of the 36 chloroform:methanol (1:1) extracts (leaf and stem extracts for all plants and an additional flower extract for H. rugulosum) exhibited minimum inhibitory concentration (MIC) values lower than 0.1mg/ml against Bacillus cereus and/or Staphylococcus aureus. The in vitro cytotoxicity [against transformed human kidney
![Research paper thumbnail of 6-Substituted imidazo[1,2-a]pyridines: Synthesis and biological activity against colon cancer cell lines HT-29 and Caco-2](https://attachments.academia-assets.com/47686836/thumbnails/1.jpg)
](European Journal of Medicinal Chemistry, 2011
A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling... more A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling reaction. Most of these compounds were found to exhibit excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst not showing significant toxicity against white blood cells. Our studies have shown that the proteolytic phase of apoptosis was initiated 2 h after treatment with these imidazoe[1,2-a]pyridines. The data suggests that the imidazo[1,2-a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via pathway(s) that include the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase 3 and caspase 8.
Pharmaceutics
Tuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is ne... more Tuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is neglected globally as evidenced by treatment and clinical care schemes, mostly extrapolated from studies in adults. The objective of this study was to formulate and evaluate a reconstitutable dry suspension (RDS) containing isoniazid, a first-line anti-tubercular agent used in the treatment and prevention of TB infection in both children and adults. The RDS formulation was prepared by direct dispersion emulsification of an aqueous-lipid particulate interphase coupled with lyophilization and dry milling. The RDS appeared as a cream-white free-flowing powder with a semi-crystalline and microparticulate nature. Isoniazid release was characterized with an initial burst up to 5 minutes followed by a cumulative release of 67.88% ± 1.88% (pH 1.2), 60.18% ± 3.33% (pH 6.8), and 49.36% ± 2.83% (pH 7.4) over 2 h. An extended release at pH 7.4 and 100% drug liberation was achieved within 300 min. The ...
International Journal of Toxicology
Potential applications of gold nanoparticles in biomedicine have increasingly been reported on ac... more Potential applications of gold nanoparticles in biomedicine have increasingly been reported on account of the ease of synthesis, bioinert characteristics, optical properties, chemical stability, high biocompatibility, and specificity. The safety of these particles remains a great concern, as there are differences among toxicity study protocols used. This article focuses on integrating results of research on the toxicological behavior of gold nanoparticles. This can be influenced by the physicochemical properties, including size, shape, surface charge, and other factors, such as methods used in the synthesis of gold nanoparticles, models used, dose, in vivo route of administration, and interference of gold nanoparticles with in vitro toxicity assay systems. Several researchers have reported toxicological studies with regard to gold nanoparticles, using various in vitro, in vivo, and in ovo models. The conflicting results concerning the toxicity of gold nanoparticles should thus be ad...
Biochemical Pharmacology, 1981
4-hr pretreatment with methotrexate antagonized the cytotoxic effect of subsequent arabinosylcyto... more 4-hr pretreatment with methotrexate antagonized the cytotoxic effect of subsequent arabinosylcytosine treatment in rat hepatoma cells of lines NISI and 3924A, but in the hepatoma line 8999R and the fibroblast line BF5, MTX pretreatment was synergistic with the arabinosylcytosine treatment. Measurement of cellular deoxyribonucleoside triphosphate concentrations showed that in those lines in which antagonism was found the dCTP increased, whereas in the lines where the drugs were synergistic the dCTP pool was decreased. Conversely, dATP levels were high when the drugs were synergistic and low when antagonism was obtained. Although methotrexate pretreatment antagonized arabinosylcytosine in N& and 3924A cells, pretreatment of these cells with the combination of methotrexate plus a purine (either hypoxanthine or 2'-deoxyadenosine) resulted in synergism with arabinosylcytosine. Deoxynucleotide pool measurements showed that methotrexate in combination with either hypoxanthine or 2'-deoxyadenosine increased dATP and decreased dCTP in the NISl and 3924A hepatoma cells. In NtSl cells, pretreatment with 2'-deoxyadenosine alone for 4 hr was synergistic with arabinosylcytosine. It was concluded that elevated dATF' pools enhanced arabinosylcytosine cytotoxicity by depleting the dCTP pool, through feedback inhibition of ribonucleotide reductase, thus causing greater inhibition of DNA biosynthesis and greater incorporation of AraCI? into nucleic acid, Methotrexate was synergistic in those cell lines where dATP accumulated and dCTP was decreased, but when methotrexate had a potent antipurine effect dCTP pools increased and arabinosylcytosine was antagonized. The synergistic interaction was more marked at cytocidal drug concentrations than it wag at growth-inhibitor doses.
Anticancer research, Dec 1, 2017
Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to c... more Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity. Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells. Rau 015 (15 μM) and curcumin (112.5 μM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 μM) and curcumin (100 μM) displayed similar effects in MCF-7 and MG-63 cells. We report on the potential of ...
Bioorganic & medicinal chemistry, Jan 15, 2016
Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthes... more Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentration of 100μM against a small panel of tumor cell lines (HL-60, K-562, Jurkat, Caco-2 and HT-29). The entire set was also tested at varying concentrations against two human glioma lines (U373 and Hs683) to obtain GI50 values, with the best results being values of ∼25μM.
Bioprocess and Biosystems Engineering, Jun 14, 2007
Cassava (Manihot esculenta Crantz) is a known source of linamarin, but difficulties associated wi... more Cassava (Manihot esculenta Crantz) is a known source of linamarin, but difficulties associated with its isolation have prevented it from being exploited as a major source. A batch adsorption process using activated carbon proved successful in its isolation, with ultrafiltration playing a pivotal role in its purification. Thirty-two minutes of contact time was required for 60 g of extract, yielding 1.7 g of purified product. Picrate paper, infra-red and 'HNMR analysis confirmed the presence and structure of linamarin. Cytotoxic effects of linamarin on MCF-7, HT-29 and HL60 cells were determined using the MTT assay. Cytotoxic effects were significantly increased in the presence of linamarase (P-glucosidase), with a 10-fold decrease in the IC50 values obtained for HL-60 cells. This study thus describes a method for the isolation and purification of linamarin from cassava, as well as its cytotoxicity potential.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2010
Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients ... more Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at Johannesburg General Hospital with those of healthy controls (26 adults) from the general population. Heparin levels in the blood samples were tested using the Chromogenix Coatest Heparin kit. The blood of the patients contained significantly lower levels of endogenous heparin compared with that of the healthy individuals, indicating that the anti-inflammatory properties afforded by heparin are absent in these patients.
Tetrahedron, 2007
A number of protected 7-isopropoxy-8-methoxy-1,2,3,6-tetrahydro-2-benzazocines were synthesized f... more A number of protected 7-isopropoxy-8-methoxy-1,2,3,6-tetrahydro-2-benzazocines were synthesized from 2-allyl-3-isopropoxy-4-methoxybenzaldehyde using ring-closing metathesis as the key step. In addition, two 9-isopropoxy-8-methoxy-3,6-dihydro-2-benzazocines were synthesized from 5-isopropoxy-4-methoxy-2-[(1E)-3-phenyl-2-propenyl]benzaldehyde, which in turn was obtained from the thermal Claisen-Cope rearrangement of 4-methoxy-3-{[(2E)-3-phenyl-2-propenyl]oxy}benzaldehyde. Finally, five of the 2-benzazocine compounds were tested for anti-cancer activity.
South African Journal of Botany, 2011
The antimicrobial activity of 35 indigenous South African Helichrysum species was determined agai... more The antimicrobial activity of 35 indigenous South African Helichrysum species was determined against six microorganisms. Seven of the 36 chloroform:methanol (1:1) extracts (leaf and stem extracts for all plants and an additional flower extract for H. rugulosum) exhibited minimum inhibitory concentration (MIC) values lower than 0.1mg/ml against Bacillus cereus and/or Staphylococcus aureus. The in vitro cytotoxicity [against transformed human kidney
European Journal of Medicinal Chemistry, 2011
A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling... more A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling reaction. Most of these compounds were found to exhibit excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst not showing significant toxicity against white blood cells. Our studies have shown that the proteolytic phase of apoptosis was initiated 2 h after treatment with these imidazoe[1,2-a]pyridines. The data suggests that the imidazo[1,2-a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via pathway(s) that include the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase 3 and caspase 8.