Synthesis and conformational studies of 5-bromo-1-[(N-substituted-carbamoyl) methyl]-7-azabenzimidazoles
- Authors: Oluwafemi, Kola A , Klein, Rosalyn , Lobb, Kevin A , Tshiwawa, Tendamudzimu , Isaacs, Michelle , Hoppe, Heinrich C , Kaye, Perry T
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452800 , vital:75171 , xlink:href="https://doi.org/10.1016/j.molstruc.2022.133811"
- Description: The Cs2CO3-catalysed condensation of 5-bromo-7-azabenzimidazole with a series of bromomethyl ketones has afforded a small library of ten, novel 5-bromo-1-[(N-substututed-carbamoyl)methyl]-7-azabenzimidazoles. Rotamerism in the products, as evidenced by the splitting of 1H- and 13C-NMR signals, is attributed to hindered internal rotation about the amide N-C(=O) bond, and has been explored using dynamic NMR (DNMR) analysis and computational methods at the GIAO B3LYP/6-311+G(2d,p) level of theory. Coalescence temperatures have been obtained for representative examples and rotational barriers determined experimentally and theoretically. A detailed theoretical analysis has been undertaken to explore conformations which may contribute to the relative populations of the s-cis and s-trans rotamers. The products have also been screened for cytotoxicity and activity against two parasitic protozoan strains (Plasmodium falciparum and Trypanosoma brucei).
- Full Text:
- Date Issued: 2022
Terminaliamide, a new ceramide and other phytoconstituents from the roots of Terminalia mantaly H. Perrier and their biological activities
- Authors: Mbosso, Emmanuel , Siwe-Noundou, Xavier , Fannang, Simone V , Song, Achille M , Assob, Jules C N , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191779 , vital:45163 , xlink:href="https://doi.org/10.1080/14786419.2019.1647425"
- Description: Terminaliamide (1), a new ceramide was isolated from the roots of Terminalia mantaly H. Perrier (Combretaceae) along with 4 known compounds (2–5). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy analysis and mass spectrometry. Compound 1 exhibited moderated antibacterial activity towards Staphylococcus aureus with MIC value of 62.5 μg/mL. The crude MeOH extract (TMr) highly reduced Plasmodium falciparum growth with an IC50 value of 10.11 μg/mL, while hexane fraction (F1) highly reduced Trypanosoma brucei brucei growth with an IC50 value of 5.60 µg/mL. All tested samples presented little or no in vitro cytotoxicity on HeLa cell line. The present work confirms that T. mantaly is medicinally important and may be used effectively as an antimicrobial, an antiplasmodial and an antitrypanosomial with promising therapeutic index.
- Full Text:
- Date Issued: 2021
A new indole alkaloid and other constituents from Monodora minor and Uvaria tanzaniae: their antitrypanosomal and antiplasmodial evaluation
- Authors: Christopher, Robert , Mgani, Quintino A , Nyandoro, Stephen S , Rousseau, Amanda L , Isaacs, Michelle , Hoppe, Heinrich C
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429347 , vital:72603 , xlink:href="https://doi.org/10.1080/14786419.2019.1710705"
- Description: Phytochemical investigation of the methanolic extract of Monodora minor Engl. and Diels (Annonaceae) stem bark yielded a new indole (E)-4-(1H-indol-5-yl)-but-3-en-2-one (1), a known indole 5-formyl-1H-indole (2) and an ubiquitous steroid sitosterol (3). The investigations of the methanolic extract of Uvaria tanzaniae Verdc. (Annonaceae) root bark yielded two previously reported C-benzylated dihydrochalcones namely uvaretin (4) and diuvaretin (5). Structures of the isolated compounds were elucidated based on NMR spectroscopy and high resolution electron ionization mass spectrometry (HR-EI-MS) data. All compounds were tested against Trypanosoma brucei brucei and Plasmodium falciparum. At a single concentration (20 μM) in the antitrypanosomal and antiplasmodial assays, compound 4 exhibited remarkable activities against T. brucei brucei and P. falciparum with percentage inhibition of 97.3% and 83.0% respectively, whereas compounds 1, 2, 3 and 5 were inactive. In a dose response antiplasmodial assay compound 4 exhibited moderate activity against P. falciparum with an IC50 value of 7.20 μM.
- Full Text:
- Date Issued: 2020
Chemical constituents, antioxidant and cytotoxicity properties of Leonotis leonurus used in the folklore management of neurological disorders in the Eastern Cape, South Africa
- Authors: Tonisi, Sipho , Okaiyeto, Kunle , Hoppe, Heinrich C , Mabinya, Leonard V , Nwodo, Uchechukwu U , Okoh, Anthony I
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429384 , vital:72606 , xlink:href="https://doi.org/10.1007/s13205-020-2126-5"
- Description: In the present study, we evaluated the phytochemical compounds and antioxidant properties of chloroform, ethanol and acetone extracts for leaves and flowers of Leonutus leonurus (L. leonurus) alongside with their cytotoxic effects on human cervical carcinoma (HeLa) cell lines. The phytochemical compounds present in the leaves and flowers of L. leonurus included; phenolics, flavonoids and alkaloids. Their radicals scavenging effects against 2, 2-diphenyl-1-picrylhydrazyl [DPPH] 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) [ABTS·+], hydrogen peroxide, nitric oxide as well as metal chelating activities showed dose-dependent activities. Gas chromatography-mass spectrometry (GCMS) analyses revealed the presence of important bioactive compounds, which are associated with antioxidant; and the extracts exhibited toxicity effect against HeLa cells. The findings from this study divulge extracts of L. leonurus as prospective sources of antioxidant and anticancer agents; and hence, further study on their neuroprotective potentials becomes imperative.
- Full Text:
- Date Issued: 2020
In Vitro Studies on Antioxidant and AntiParasitic Activities of Compounds Isolated from Rauvolfia caffra Sond
- Authors: Tlhapi, Dorcas B , Ramaite, Isaiah D , Anokwuru, Chinedu P , van Ree, Teunis , Hoppe, Heinrich C
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/425993 , vital:72305 , xlink:href="https://doi.org/10.3390/molecules25173781"
- Description: As part of an ongoing study of natural products from local medicinal plants, the methanol extract of stem bark of Rauvolfia caffra Sond was investigated for biological activity. Column chromatography and preparative thin-layer chromatography were used to isolate lupeol (1), raucaffricine (2), N-methylsarpagine (3), and spegatrine (4). The crude extract, fractions and isolated compounds were tested for anti-oxidant, antitrypanosomal and anti-proliferation activities. Two fractions displayed high DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging activity and reducing power with IC50 (The half maximal inhibitory concentration) and IC0.5 values of 0.022 ± 0.003 mg/mL and 0.036 ± 0.007 mg/mL, and 0.518 ± 0.044 mg/mL and 1.076 ± 0.136 mg/mL, respectively. Spegatrine (4) was identified as the main antioxidant compound in R. caffra with IC50 and IC0.5 values of 0.119 ± 0.067 mg/mL and 0.712 ± 0 mg/mL, respectively. One fraction displayed high antitrypanosomal activity with an IC50 value of 18.50 μg/mL. However, the major constituent of this fraction, raucaffricine (2), was not active. The crude extract, fractions and pure compounds did not display any cytotoxic effect at a concentration of 50 μg/mL against HeLa cells. This study shows directions for further in vitro studies on the antioxidant and antitrypanosomal activities of Rauvolfia caffra Sond.
- Full Text:
- Date Issued: 2020
Plant-Based Synthesis of Silver Nanoparticles Using Aqueous Leaf Extract of Salvia officinalis: Characterization and its Antiplasmodial Activity
- Authors: Okaiyeto, Kunle , Hoppe, Heinrich C , Okoh, Anthony I
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/429472 , vital:72613 , xlink:href="https://doi.org/10.1007/s10876-020-01766-y"
- Description: In the present study, an aqueous leaf extract of Salvia officinalis was used to synthesize silver nanoparticles (AgNPs) and characterized with different techniques such as UV–vis spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction (XRD), Scanning electron microscope (SEM), Energy dispersive X-ray spectroscopy (EDX), Transmission electron microscope (TEM) and thermogravimetric analysis (TGA). Subsequently, its cytotoxic effect against human cervix adenocarcinoma (HeLa) cells and antiplasmodial activity against Plasmodium falciparum were investigated. UV–vis spectrum of AgNPs displayed an absorption peak at 323 nm and TEM result revealed it to be spherical in shape with average size of 41 nm. FTIR results highlighted the key bioactive compounds that could be responsible for the reduction and capping of AgNPs and XRD analysis showed its crystalline nature with a face-centered cubic (fcc) structure. The synthesized AgNPs was found to be less cytotoxic against HeLa cells line and demonstrated good antiplasmodial potential (IC50 = 3.6 µg/mL). Findings from this study indicated that the AgNPs could serve as a template in the development of new drugs for the control of malaria and hence, further study is needed to identify and characterize the potent molecules that suppress the malaria parasite.
- Full Text:
- Date Issued: 2020
Synthesis and anti-parasitic activity of N-benzylated phosphoramidate Mg2+-chelating ligands
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Mnkandhla, Dumisani , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/451171 , vital:75025 , xlink:href="https://doi.org/10.1016/j.bioorg.2020.104280"
- Description: A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg2+-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-D-xylulose-5- phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg2+- chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC50 values of 5.6–16.4 µM against Plasmodium falciparum parasites and IC50 values of 5.2 – 10.2 µM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)5 support their potential as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
Synthesis and biological evaluation of bis-N2, N2′-(4-hydroxycoumarin-3-yl) ethylidene]-2, 3-dihydroxysuccinodihydrazides
- Authors: Manyeruke, Meloddy H , Tshiwawa, Tendamudzimu , Hoppe, Heinrich C , Isaacs, Michelle , Seldon, Ronnett , Warner, Digby F , Krause, Rui W M , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193430 , vital:45331 , xlink:href="https://doi.org/10.1016/j.bmcl.2019.126911"
- Description: A series of N2,N2′-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC50 = 3.5 μM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 μM) activity.
- Full Text:
- Date Issued: 2020
Antiplasmodial Activity of the n-Hexane Extract from Pleurotus ostreatus (Jacq. ex. Fr) P. Kumm
- Authors: Afieroho, Ozadheoghene E , Siwe-Noundou, Xavier , Onyia, Chiazor P , Festus, Osamuyi H , Chukwu, Elizabeth C , Adedokun, Olutayo M , Isaacs, Michelle , Hoppe, Heinrich C , Krause, Rui W M , Abo, Kio A
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/194981 , vital:45516 , xlink:href="https://doi.org/10.4274/tjps.18894"
- Description: Objectives: Several mushrooms species have been reported to be nematophagous and antiprotozoan. This study reported the antiplasmodial and cytotoxic properties of the n-hexane extract from the edible mushroom Pleurotus ostreatus and the isolation of a sterol from the extract. Materials and Methods: Antiplasmodial and cytotoxicity assays were done in vitro using the plasmodium lactate dehydrogenase assay and human HeLa cervical cell lines, respectively. The structure of the isolated compound from the n-hexane extract was elucidated using spectroscopic techniques. Results: The n-hexane extract (yield: 0.93% w/w) showed dose dependent antiplasmodial activity with the trend in parasite inhibition of: chloroquine (IC50=0.016 μg/mL) > n-hexane extract (IC50=25.18 μg/mL). It also showed mild cytotoxicity (IC50>100 μg/mL; selectivity index >4) compared to the reference drug emetine (IC50=0.013 μg/mL). The known sterol, ergostan-5,7,22-trien-3-ol, was isolated and characterized from the extract. Conclusion: This study reporting for the first time the antiplasmodial activity of P. ostreatus revealed its nutraceutical potential in the management of malaria.
- Full Text:
- Date Issued: 2019
In vitro antimalarial, antitrypanosomal and HIV-1 integrase inhibitory activities of two Cameroonian medicinal plants
- Authors: Fouokeng, Yannick , Feumo Feusso, H M , Mbosso Teinkela, Jean E , Siwe-Noundou, Xavier , Wintjens, René T , Isaacs, Michelle , Hoppe, Heinrich C , Krause, Rui W M , Azébazé, Anatole G B , Vardamides, Juliette C
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195014 , vital:45519 , xlink:href="https://doi.org/10.1016/j.sajb.2018.10.008"
- Description: Antiplasmodial, antitrypanosomal and anti-HIV-1 activities of crude extracts, fractions and some isolated compounds from two Cameroonian medicinal plants: Antrocaryon klaineanum Pierre (Anacardiaceae) and Diospyros conocarpa Gürke ex K. Schum. (Ebenaceae) were assessed. The phytochemical studies led to the isolation of eight compounds (1–8) from Diospyros conocarpa and six compounds (6, 9–13) from Antrocaryon klaineanum. These compounds were identified as mangiferolic acid (1), 3β, 22(S)-dihydroxycycloart-24E-en-26-oic acid (2), lupeol (3), aridanin (4), betulin (5), betulinic acid (6), bergenin (7), D-quercitol(8), entilin C(9), entilin A(10), antrocarine A(11), 7R,20(S)-dihydroxy-4,24(28)-ergostadien-3-one(12) and stigmasterol glucoside (13). The criteria for activity were set as follows: an IC50 value more than 10 μg/mL for crude extracts and more than 1 μg/mL for pure compounds. The hexane/ethyl acetate (1:1) fraction of A.klaineanum root bark (AKERF1) and the hexane/ethyl acetate (1:1) fraction of A.klaineanum trunk bark (AKETF1) presented the strongest antiplasmodial activities with IC50 values of 0.4 and 4.4 μg/mL, respectively. Aridanin (4) and antrocarine A(11), as well as the crude extract of D.conocarpa roots (EDCR), AKERF1 and AKETF1 showed moderate trypanocidal effects. The crude extract of A.klaineanum root bark (AKER) and AKETF1 exhibited attractive activities on HIV-1 integrase with IC50 values of 1.96 and 24.04 μg/mL, respectively. The results provide baseline information on the use of A.klaineanum and D.conocarpa extracts, as well as certain components, as sources of new antiplasmodial, antitrypanosomal and anti-HIV drugs.
- Full Text:
- Date Issued: 2019
Synthesis of N-Substituted phosphoramidic acid esters as “reverse” fosmidomycin analogues
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Klein, Rosalyn , Lobb, Kevin A , Kaye, Perry T
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/443238 , vital:74101 , https://doi.org/10.1016/j.tet.2019.02.003
- Description: An efficient synthetic pathway to a series of novel “reverse” fosmidomycin analogues has been developed, commencing from substituted benzylamines. In these analogues, the fosmidomycin hydroxamate moiety is reversed and the tetrahedral methylene carbon adjacent to the phosphonate moiety is replaced by a nitrogen atom bearing different benzyl groups. The resulting phosphonate esters were designed as potential antimalarial “pro-drugs”.
- Full Text:
- Date Issued: 2019
Synthesis of N-Substituted phosphoramidic acid esters as “reverse” fosmidomycin analogues
- Authors: Adeyemi, Christiana M , Hoppe, Heinrich C , Isaacs, Michelle , Klein, Rosalyn , Lobb, Kevin A , Kaye, Perry T
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447196 , vital:74591 , xlink:href="https://doi.org/10.1016/j.tet.2019.02.003"
- Description: An efficient synthetic pathway to a series of novel “reverse” fosmidomycin analogues has been developed, commencing from substituted benzylamines. In these analogues, the fosmidomycin hydroxamate moiety is reversed and the tetrahedral methylene carbon adjacent to the phosphonate moiety is replaced by a nitrogen atom bearing different benzyl groups. The resulting phosphonate esters were designed as potential antimalarial “pro-drugs”.
- Full Text:
- Date Issued: 2019
Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion
- Authors: Ziningwa, Tawanda , Achilonu, Ikechukwu , Hoppe, Heinrich C , Prinsloo, Earl , Dirr, Heinrich W , Shonhai, Addmore
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431765 , vital:72802 , xlink:href="https://doi.org/10.1007/s12192-016-0678-4"
- Description: The role of molecular chaperones, among them heat shock proteins (Hsps), in the development of malaria parasites has been well documented. Hsp70s are molecular chaperones that facilitate protein folding. Hsp70 proteins are composed of an N-terminal nucleotide binding domain (NBD), which confers them with ATPase activity and a Cterminal substrate binding domain (SBD). In the ADPbound state, Hsp70 possesses high affinity for substrate and releases the folded substrate when it is bound to ATP. The two domains are connected by a conserved linker segment. Hsp110 proteins possess an extended lid segment, a feature that distinguishes them from canonical Hsp70s.
- Full Text:
- Date Issued: 2016
Supplementary Material Synthesis and biological evaluation of (E)-cinnamic acid,(E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl) vinyl] thiazole derivatives
- Authors: Olawode, Emmanuel O , Tandlich, Roman , Prinsloo, Earl , Isaacs, Michelle , Hoppe, Heinrich C , Seldon, Ronnett , Warner, Digby F , Steenkamp, Vanessa , Kaye, Perry T
- Date: 2016
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431778 , vital:72803 , xlink:href=" https://www.arkat-usa.org/get-file/59868/"
- Description: The screening was conducted using multi-well plates which are suited for HeLa cells in the log phase of growth with final cell density > 10 cells/cm. Each experiment normally includes a blank control, containing medium without the cells.28,45 Non-contaminated HeLa cells (6.57 x 105 cells per well) in media were allowed to grow in the incubator under an atmosphere of 5% CO2 at 37 0C for 24 h. To each well was dispensed 200 µL of HeLa culture, containing 6.57 x 105 cells under LabEAir laminar flow hood (Vivid Air, South Africa); 20 µL of resazurin dye (Sigma TOX-8) and test compound (50 µL) were added, which were then incubated in the presence of 5% CO2 at 37 0C for 24 hours in a shaker, to enhance the distribution of the dye. The absorbance of each well was measured with Bio-tek Power Wave X fluorometer (Beijing, China), and increases in fluorescence was monitored at a wavelength of 590 nm, using an excitation wavelength of 560 nm.
- Full Text:
- Date Issued: 2016
Overexpression, Purification and Characterisation of the Plasmodium falciparum Hsp70-z (PfHsp70-z) Protein
- Authors: Zininga, Tawanda , Achilonu, Ikechukwu , Hoppe, Heinrich C , Prinsloo, Earl , Dirr, Heinrich W , Shonhai, Addmore
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431719 , vital:72799 , xlink:href="https://doi.org/10.1371/journal.pone.0129445"
- Description: Six Hsp70-like genes are represented on the genome of Plasmodium falciparum. Of these two occur in the cytosol: P. falciparum Hsp70-z (PfHsp70-z) and PfHsp70-1. PfHsp70-1 is a well characterised canonical Hsp70 that facilitates protein quality control and is crucial for the development of malaria parasites. There is very little known about PfHsp70-z. However, PfHsp70-z is known to be essential and is implicated in suppressing aggregation of asparagine-rich proteins of P. falciparum. In addition, its expression at the clinical stage of malaria correlates with disease prognosis. Based on structural evidence PfHsp70-z belongs to the Hsp110 family of proteins. Since Hsp110 proteins have been described as nucleotide exchange factors (NEFs) of their canonical Hsp70 counterparts, it has been speculated that PfHsp70-z may serve as a NEF of PfHsp70-1. In the current study, P. falciparum cells cultured in vitro were subjected to heat stress, triggering the enhanced expression of PfHsp70-z. Biochemical assays conducted using recombinant PfHsp70-z protein demonstrated that the protein is heat stable and possesses ATPase activity. Furthermore, we observed that PfHsp70-z is capable of self-association. The structural-functional features of PfHsp70-z provide further evidence for its role as a chaperone and possible nucleotide exchange factor of PfHsp70-1.
- Full Text:
- Date Issued: 2015
Plasmodium falciparum Hop (PfHop) interacts with the Hsp70 chaperone in a nucleotide-dependent fashion and exhibits ligand selectivity
- Authors: Zininga, Tawanda , Makumire, Stanley , Gitau, Grace W , Njunge, James M , Pooe, Ofentse J , Klimek, Hanna , Scheurr, Robina , Raifer, Hartmann , Prinsloo, Earl , Przyborski, Jude M , Hoppe, Heinrich C , Shonhai, Addmore
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431752 , vital:72801 , xlink:href=" https://doi.org/10.1371/journal.pone.0135326"
- Description: Heat shock proteins (Hsps) play an important role in the development and pathogenicity of malaria parasites. One of the most prominent functions of Hsps is to facilitate the folding of other proteins. Hsps are thought to play a crucial role when malaria parasites invade their host cells and during their subsequent development in hepatocytes and red blood cells. It is thought that Hsps maintain proteostasis under the unfavourable conditions that malaria parasites encounter in the host environment. Although heat shock protein 70 (Hsp70) is capable of independent folding of some proteins, its functional cooperation with heat shock protein 90 (Hsp90) facilitates folding of some proteins such as kinases and steroid hormone receptors into their fully functional forms. The cooperation of Hsp70 and Hsp90 occurs through an adaptor protein called Hsp70-Hsp90 organising protein (Hop). We previously characterised the Hop protein from Plasmodium falciparum (PfHop). We observed that the protein co-localised with the cytosol-localised chaperones, PfHsp70-1 and PfHsp90 at the blood stages of the malaria parasite. In the current study, we demonstrated that PfHop is a stress-inducible protein. We further explored the direct interaction between PfHop and PfHsp70-1 using far Western and surface plasmon resonance (SPR) analyses.
- Full Text:
- Date Issued: 2015
Guardian of the furnace: mitochondria, TRAP1, ROS and stem cell maintenance
- Authors: Kadye, Rose , Kramer, Adam H , Joos-Vandewalle, Julia , Parsons, Michelle , Njengele, Zikhona , Hoppe, Heinrich C , Prinsloo, Earl
- Date: 2014
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/431119 , vital:72745 , xlink:href="https://doi.org/10.1002/iub.1234"
- Description: Mitochondria are key to eukaryotic cell survival and their activity is linked to generation of reactive oxygen species (ROS) which in turn acts as both an intracellular signal and an effective executioner of cells with regards to cellular senescence. The mitochondrial molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1) is often termed the cytoprotective chaperone for its role in cancer cell survival and protection from apoptosis. Here, we hypothesize that TRAP1 serves to modulate mitochondrial activity in stem cell maintenance, survival and differentiation.
- Full Text:
- Date Issued: 2014
Transformations of manool. Tri-and tetracyclic norditerpenoids with in vitro activity against plasmodium falciparum
- Authors: van Wyk, Albert W W , Lobb, Kevin A , Mino, Caira R , Hoppe, Heinrich C , Davies-Coleman, Michael T
- Date: 2007
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/450511 , vital:74956 , xlink:href="https://doi.org/10.1021/np0701071"
- Description: The known 17-norisopimar-15-ene-8‚,13‚-diol (5) and five new semisynthetic norditerpenoids, ethyl 17-norabiet-13-(15)-E-en-8‚-ol-16-oate (6), ethyl 17-norabiet-13(15)-Z-en-8‚-ol-16-oate (7), 17-norpimaran-13R-ethoxy-8,16-olactone(8), 17-norisopimarane-8‚,15-diol (9), and 17-norarabiet-13(15)-ene-8‚,16-diol (10), were prepared from manool (11).Standard spectroscopic data including X-ray crystal analysis were used to determine the structures of5-10. All fivecompounds exhibited in Vitroantiplasmodial activity against the malarial parasitePlasmodium falciparumat varyingÌgmL-1concentrations.
- Full Text:
- Date Issued: 2007