SwePub - search: WFRF:(Alao John Patrick)

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1.	Abdissa, Negera, et al. (author) Cytotoxic Quinones from the roots of Aloe dawei 2014 In: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 19:3, s. 3264-3273 Journal article (peer-reviewed)abstract Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC50 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells.
2.	Alao, John Patrick, 1973, et al. (author) Caffeine as a tool for investigating the integration of Cdc25 phosphorylation, activity and ubiquitin-dependent degradation in Schizosaccharomyces pombe. 2020 In: Cell Division. - : Springer Science and Business Media LLC. - 1747-1028. ; 15 Research review (peer-reviewed)abstract The evolutionarily conserved Cdc25 phosphatase is an essential protein that removes inhibitory phosphorylation moieties on the mitotic regulator Cdc2. Together with the Wee1 kinase, a negative regulator of Cdc2 activity, Cdc25 is thus a central regulator of cell cycle progression in Schizosaccharomyces pombe. The expression and activity of Cdc25 is dependent on the activity of the Target of Rapamycin Complex 1 (TORC1). TORC1 inhibition leads to the activation of Cdc25 and repression of Wee1, leading to advanced entry into mitosis. Withdrawal of nitrogen leads to rapid Cdc25 degradation via the ubiquitin- dependent degradation pathway by the Pub1 E3- ligase. Caffeine is believed to mediate the override of DNA damage checkpoint signalling, by inhibiting the activity of the ataxia telangiectasia mutated (ATM)/Rad3 homologues. This model remains controversial, as TORC1 appears to be the preferred target of caffeine in vivo. Recent studies suggest that caffeine induces DNA damage checkpoint override by inducing the nuclear accumulation of Cdc25 in S. pombe. Caffeine may thus modulate Cdc25 activity and stability via inhibition of TORC1. A clearer understanding of the mechanisms by which caffeine stabilises Cdc25, may provide novel insights into how TORC1 and DNA damage signalling is integrated.
3.	Alao, John Patrick, 1973 (author) Caffeine, cyclin D1 and cell proliferation 2012 In: Tea in Health and Disease Prevention. - : Academic Press. - 9780123849373 ; , s. 1159-1169 Book chapter (other academic/artistic)abstract Although well characterized as an inhibitor of DNA damage-induced checkpoint signaling, caffeine has also been reported to delay G1-S-phase cell cycle progression in various cell lines. This activity is known to result from the inhibitory effect of caffeine on cyclin-dependent kinase 4/6 activity and occurs independently of p53. Ataxia telangiectasia mutated, a proposed target of caffeine, is required for insulin-induced protein kinase B/Akt phosphorylation and thus indirectly enhances cyclin-dependent kinase 4/6 activity by promoting cyclin D1 synthesis and stability. Caffeine and a selective ataxia telangiectasia mutated inhibitor (KU55933) have been shown to suppress Akt phosphorylation following exposure to insulin. Furthermore, both caffeine and KU55933 have been shown to suppress cyclin D1 expression. These studies suggest that caffeine suppresses G1-S-phase progression by indirectly inhibiting cyclin D1 synthesis and cyclin dependent kinase 4/6 activity. The precise in vivo target(s) of caffeine has not, however, been clearly defined.
4.	Alao, John Patrick, 1973, et al. (author) Caffeine stabilises fission yeast Wee1 in a Rad24-dependent manner but attenuates Its expression in response to DNA damage. 2020 In: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:10 Journal article (peer-reviewed)abstract The widely consumed neuroactive compound caffeine has generated much interest due to its ability to override the DNA damage and replication checkpoints. Previously Rad3 and its homologues was thought to be the target of caffeine's inhibitory activity. Later findings indicate that the Target of Rapamycin Complex 1 (TORC1) is the preferred target of caffeine. Effective Cdc2 inhibition requires both the activation of the Wee1 kinase and inhibition of the Cdc25 phosphatase. The TORC1, DNA damage, and environmental stress response pathways all converge on Cdc25 and Wee1. We previously demonstrated that caffeine overrides DNA damage checkpoints by modulating Cdc25 stability. The effect of caffeine on cell cycle progression resembles that of TORC1 inhibition. Furthermore, caffeine activates the Sty1 regulated environmental stress response. Caffeine may thus modulate multiple signalling pathways that regulate Cdc25 and Wee1 levels, localisation and activity. Here we show that the activity of caffeine stabilises both Cdc25 and Wee1. The stabilising effect of caffeine and genotoxic agents on Wee1 was dependent on the Rad24 chaperone. Interestingly, caffeine inhibited the accumulation of Wee1 in response to DNA damage. Caffeine may modulate cell cycle progression through increased Cdc25 activity and Wee1 repression following DNA damage via TORC1 inhibition, as TORC1 inhibition increased DNA damage sensitivity.
5.	Alao, John Patrick, 1973, et al. (author) Caffeine stabilizes Cdc25 independently of Rad3 in Schizosaccharomyces pombe contributing to checkpoint override 2014 In: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 92:4, s. 777-796 Journal article (peer-reviewed)abstract Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both Schizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S.pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S.pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25.
6.	Alao, John Patrick, 1973 (author) G1 Phase cyclins in cancer development and progression 2009 In: Checkpoint controls and targets in cancer therapy. Cancer drug discovery and development. (Zahid H. Siddik, editor). - New York : Humana Press. - 9781607611776 ; , s. 123-153 Book chapter (other academic/artistic)abstract Cyclin D1 and cyclin E are rate limiting for progression through G1 and entry into S phase during the cell cycle. Cyclin D1 plays a crucial role in linking favourable environmental conditions with cell cycle progression. Cyclin D1 indirectly induces cyclin E expression and activation which is required for entry into S phase. The deregulated expression of either cyclin would thus greatly impact on a cell’s ability to effectively regulate cell cycle progression. It perhaps not surprising therefore, that both cyclin D1 and cyclin E play important roles in the development and progression of cancer. This chapter explores the roles of these cyclins in cancer. For clarity, the major focus will be on the well characterized roles of cyclin D1 and cyclin E and thus to a lesser extent on other G1 cyclins such as cyclins D2 and D3. This chapter summarizes the evidence linking cyclin D1 and cyclin E to cancer development and progression. The cellular pathways that underlie the deregulated expression of the G1 cyclins in cancer, as well as their oncogenic roles are also discussed. Lastly, this chapter explores the potential of these cyclins to serve as therapeutic targets in cancer therapy.
7.	Alao, John Patrick, 1973, et al. (author) Hyperosmosis enhances radiation and hydroxyurea resistance of S. pombe checkpoint mutants through the spindle checkpoint and delayed cytokinesis 2010 In: Molecular Microbiology. - : Wiley. - 0950-382X. ; 77:1, s. 143-157 Journal article (peer-reviewed)abstract The DNA damage and stress response pathways interact to regulate cellular responses to genotoxins and environmental stresses. How these pathways interact in Schizosaccharomyces pombe is not well understood. We demonstrate that osmotic stress suppresses the DNA damage sensitivity of checkpoint mutants, and that this occurs through three distinct cell cycle delays. A delay in G2/M is dependent on Srk1. Progression through mitosis is halted by a Mad2-dependent spindle checkpoint. Finally, cytokinesis is impaired by modulating Cdc25 expression. These three delays, imposed by osmotic stress, together compensate for the loss of checkpoint signalling.
8.	Alao, John Patrick, 1973, et al. (author) Inhibition of type I histone deacetylase increases resistance of checkpoint-deficient cells to genotoxic agents through mitotic delay 2009 In: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 8, s. 2606-2615 Journal article (peer-reviewed)abstract Histone deacetylase (HDAC) inhibitors potently inhibit tumor growth and are currently being evaluated for their efficacy as chemosensitizers and radiosensitizers. This efficacy is likely to be limited by the fact that HDACinhibitors also induce cell cycle arrest. Deletion of the class I HDACRpd3 has been shown to specifically suppress the sensitivity of Saccharomyces cerevisiae DNA damage checkpoint mutants to UV and hydroxyurea. We show that in the fission yeast Schizosaccharomyces pombe, inhibition of the homologous class I HDACspe cifically suppresses the DNA damage sensitivity of checkpoint mutants. Importantly, the prototype HDACinhibitor Trichostatin A also suppressed the sensitivity of DNA damage checkpoint but not of DNA repair mutants to UV and HU. TSA suppressed DNA damage activity independently of the mitogen-activated protein kinase–dependent and spindle checkpoint pathways. We show that TSA delays progression into mitosis and propose that this is the main mechanism for suppression of the DNA damage sensitivity of S. pombe checkpoint mutants, partially compensating for the loss of the G2 checkpoint pathway. Our studies also show that the ability of HDACinhibitors to suppress DNA damage sensitivity is not species specific. Class I HDACs are the major target of HDAC inhibitors and cancer cells are often defective in checkpoint activation. Effective use of these agents as chemosensitizers and radiosensitizers may require specific treatment schedules that circumvent their inhibition of cell cycle progression.
9.	Alao, John Patrick, 1973, et al. (author) Rad3 and Sty1 function in S. pombe: an integrated response to DNA damage and environmental stress? 2008 In: Molecular Microbiology. - : Wiley. - 0950-382X. ; 68, s. 246-254 Research review (peer-reviewed)abstract In Schizosaccharomyces pombe, the Ataxia Telangiectasia-mutated (Atm)/Atm and Rad 3 Related (Atr) homologue Rad3 is an essential regulator of the response to DNA damage and stalled replication forks. Rad3 activates the downstream kinases Chk1 and Cds1. These kinases in turn inhibit cell cycle progression by mediating Cdc2 phosphorylation. Studies in both yeast and mammalian cells suggest additional roles for Rad3 in regulating cellular responses to environmental stress. In S. pombe, cellular responses to various environmental stresses are regulated primarily through the stress-activated MAP kinase p38 homologue Sty1. An important function of Sty1 is to drive cells rapidly through mitosis by facilitating the accumulation of Cdc25. Interestingly, Sty1 is activated simultaneously with Rad3 following exposure to UV radiation or ionizing radiation (IR). Similarly, exposure to environmental stresses induces the expression of rad3+, cds1+ and other checkpoint regulator genes. It is currently unclear how the pathways regulated by Sty1 and Rad3 and their opposing effects on mitosis are integrated. Recent studies suggest that Sty1 and Rad3 function together to regulate the expression of several stress response genes following exposure to IR. In this review, we discuss current knowledge on the interaction of Rad3/Atm and Sty1/p38 in regulating cellular responses to environmental stress and DNA damage.
10.	Alao, John Patrick, 1973, et al. (author) Role of glycogen synthase kinase 3 beta (GSK3 beta) in mediating the cytotoxic effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast cancer cells 2006 In: MOLECULAR CANCER. - : Springer Science and Business Media LLC. - 1476-4598. ; 5 Journal article (peer-reviewed)
11.	Alao, John Patrick, 1973, et al. (author) Selective inhibition of RET mediated cell proliferation in vitro by the kinase inhibitor SPP86 2014 In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 14:853 Journal article (peer-reviewed)abstract BackgroundThe RET tyrosine kinase receptor has emerged as a target in thyroid and endocrine resistant breast cancer. We previously reported the synthesis of kinase inhibitors with potent activity against RET. Herein, we have further investigated the effect of the lead compound SPP86 on RET mediated signaling and proliferation. Based on these observations, we hypothesized that SPP86 may be useful for studying the cellular activity of RET.MethodsWe compared the effects of SPP86 on RET-induced signaling and proliferation in thyroid cancer cell lines expressing RET-PTC1 (TPC1), or the activating mutations BRAFV600E (8505C) and RASG13R (C643). The effect of SPP86 on RET- induced phosphatidylinositide 3-kinases (PI3K)/Akt and MAPK pathway signaling and cell proliferation in MCF7 breast cancer cells was also investigated.ResultsSPP86 inhibited MAPK signaling and proliferation in RET/PTC1 expressing TPC1 but not 8505C or C643 cells. In TPC1 cells, the inhibition of RET phosphorylation required co-exposure to SPP86 and the focal adhesion kinase (FAK) inhibitor PF573228. In MCF7 cells, SPP86 inhibited RET- induced phosphatidylinositide 3-kinases (PI3K)/Akt and MAPK signaling and estrogen receptorα (ERα) phosphorylation, and inhibited proliferation to a similar degree as tamoxifen. Interestingly, SPP86 and PF573228 inhibited RET/PTC1 and GDNF- RET induced activation of Akt and MAPK signaling to a similar degree.ConclusionSPP86 selectively inhibits RET downstream signaling in RET/PTC1 but not BRAFV600E or RASG13R expressing cells, indicating that downstream kinases were not affected. SPP86 also inhibited RET signaling in MCF7 breast cancer cells. Additionally, RET- FAK crosstalk may play a key role in facilitating PTC1/RET and GDNF- RET induced activation of Akt and MAPK signaling in TPC1 and MCF7 cells.
12.	Alao, John Patrick, 1973, et al. (author) Suppression of sensitivity to drugs and antibiotics by high external cation concentrations in fission yeast 2015 In: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3 Journal article (peer-reviewed)abstract Background Potassium ion homeostasis plays an important role in regulating membrane potential and therefore resistance to cations, antibiotics and chemotherapeutic agents in Schizosaccharomyces pombe and other yeasts. However, the precise relationship between drug resistance in S. pombe and external potassium concentrations (particularly in its natural habitats) remains unclear. S. pombe can tolerate a wide range of external potassium concentrations which in turn affect plasma membrane polarization. We thus hypothesized that high external potassium concentrations suppress the sensitivity of this yeast to various drugs. Methods We have investigated the effect of external KCl concentrations on the sensitivity of S. pombe cells to a wide range of antibiotics, antimicrobial agents and chemotherapeutic drugs. We employed survival assays, immunoblotting and microscopy for these studies. Results We demonstrate that KCl, and to a lesser extent NaCl and RbCl can suppress the sensitivity of S. pombe to a wide range of antibiotics. Ammonium chloride and potassium hydrogen sulphate also suppressed drug sensitivity. This effect appears to depend in part on changes to membrane polarization and membrane transport proteins. Interestingly, we have found little relationship between the suppressive effect of KCl on sensitivity and the structure, polarity or solubility of the various compounds investigated. Conclusions High concentrations of external potassium and other cations suppress sensitivity to a wide range of drugs in S. pombe. Potassium-rich environments may thus provide S. pombe a competitive advantage in nature. Modulating potassium ion homeostasis may sensitize pathogenic fungi to antifungal agents.
13.	Alao, John Patrick, 1973, et al. (author) The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation 2009 In: Radiation Oncology. ; 4 Journal article (peer-reviewed)abstract The ataxia telangiectasia mutated (ATM) and the ATM- related (ATR) kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets, since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM (KU55933) or ATM and ATR (CGK733) have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p21 expression required for the survival of these cells. The precise molecular pharmacology of these agents however, is not well characterized. Herein, we report that caffeine, CGK733, and to a lesser extent KU55933, inhibit the proliferation of otherwise untreated human cancer and non-transformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and CGK733 was associated with a rapid decline in cyclin D1 protein levels and a reduction in the levels of both phosphorylated and total retinoblastoma protein (RB). Our studies suggest that observations based on the effects of these compounds on cell proliferation and survival must be interpreted with caution. The differential effects of caffeine/ CGK733 and KU55933 on cyclin D1 protein levels suggest that these agents will exhibit dissimilar molecular pharmacological profiles.
14.	Alao, John Patrick, 1973 (author) The ATM regulated DNA damage response pathway as a chemo- and radiosensitisation target 2009 In: Expert Opinion on Drug Discovery. - : Informa Healthcare. - 1746-0441 .- 1746-045X. ; 4:5, s. 495-505 Research review (peer-reviewed)abstract Background: Ataxia telangiectasia mutated (ATM) kinase plays a central role in maintaining genomic stability and regulating the response of cells exposed to agents that induce DNA damage. ATM regulated pathways also enable cancer cells to resist the lethal effects of genotoxic cancer treatments. The pharmacological inhibition of these pathways may thus sensitise cancer cells to chemo- and radiotherapy. Objectives: This review outlines the role of ATM in regulating components of the DNA damage response pathway. The potential of inhibitors that target ATM regulated pathways to act as chemo- and radiosensitising agents is also discussed. Results/conclusions: Inhibitors that target ATM and its downstream targets are likely to be effective as chemo- and/ or radiosensitising agents. Their effective use will, however, require a better understanding of when and how ATM influences the sensitivity of cancer cells to particular genotoxic agents.
15.	Alao, John Patrick, 1973 (author) The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention 2007 In: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 6 Research review (peer-reviewed)abstract Cyclin D1 is an important regulator of cell cycle progression and can function as a transcriptionl co-regulator. The overexpression of cyclin D1 has been linked to the development and progression of cancer. Deregulated cyclin D1 degradation appears to be responsible for the increased levels of cyclin D1 in several cancers. Recent findings have identified novel mechanisms involved in the regulation of cyclin D1 stability. A number of therapeutic agents have been shown to induce cyclin D1 degradation. The therapeutic ablation of cyclin D1 may be useful for the prevention and treatment of cancer. In this review, current knowledge on the regulation of cyclin D1 degradation is discussed. Novel insights into cyclin D1 degradation are also discussed in the context of ablative therapy. A number of unresolved questions regarding the regulation of cellular cyclin D1 levels are also addressed.
16.	Dinér, Peter, 1976, et al. (author) Preparation of 3-Substituted-1-Isopropyl-1H-pyrazolo 3,4-d pyrimidin-4-amines as RET Kinase Inhibitors 2012 In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:10, s. 4872-4876 Journal article (peer-reviewed)abstract A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM.
17.	Dinér, Peter, et al. (author) Preparation of 3-Substituted-1-Isopropyl-1H-pyrazolo 3,4-d pyrimidin-4-amines as RET Kinase Inhibitors 2012 In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55 4872-4876:10, s. 4872-4876 Journal article (peer-reviewed)
18.	Dyrager, Christine, 1975, et al. (author) Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors 2011 In: Journal of Medicinal Chemistry. ; 54, s. 7427-7431 Journal article (peer-reviewed)abstract 3-(4-Fluorophenyl)-2-(4-pyridyl)chromone derivatives were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38α inhibitors with IC(50) in the low nanomolar range (e.g., IC(50) = 17 nm). The inhibitors showed excellent selectivity profiles when tested on a panel of 62 kinases, as well as efficient inhibition of p38 signaling in human breast cancer cells.
19.	Dyrager, Christine, et al. (author) Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors 2011 In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54 Journal article (peer-reviewed)
20.	Dyrager, Christine, et al. (author) Design, Synthesis and Biological Evaluation of Chromone-based p38 MAP Kinase Inhibitors 2011 In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:20, s. 7427-7431 Journal article (peer-reviewed)abstract A series of 3-(4-fluorophenyl)-2-(4-pyridyl)-chromone derivs. were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38 inhibitors with IC50 values in the low nanomolar range (e.g. 8a; IC50 = 17 nm). Addnl., the inhibitors (8a and 8e) demonstrate an excellent selectivity profile towards the p38 kinase among other kinases, as well as inhibition (8e) of p38 signaling in human breast cancer cells. [on SciFinder(R)]
21.	Endale, Milkyas, 1980, et al. (author) Anthraquinones of the roots of Pentas micrantha 2013 In: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 18:1, s. 311-321 Journal article (peer-reviewed)abstract Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low cytotoxicity (>450 μg/mL, MCF-7 cell line). Chromatographic separation of the extract yielded nine anthraquinones, of which 5,6-dihydroxylucidin-11-O-methyl ether is new. Isolation of a munjistin derivative from the genus Pentas is reported here for the first time. The isolated constituents were identified by NMR and mass spectrometric techniques and showed low antiplasmodial activities.
22.	Endale, Milkyas, et al. (author) Antiplasmodial Quinones from Pentas longiflora and Pentas lanceolata 2012 In: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 78:1, s. 31-35 Journal article (peer-reviewed)abstract The dichloromethane/methanol (1 : 1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC50 = 0.9-3 µg/mL) in vitro antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. Chromatographic separation of the extract of Pentas longiflora led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC50 values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones (4-11, IC50 = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three - nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10) - are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.
23.	Endale, Milkyas, 1980, et al. (author) Busseihydroquinones A-D from the Roots of Pentas bussei 2012 In: Journal of Natural Products. - : American Chemical Society (ACS). - 1520-6025 .- 0163-3864. ; 75, s. 1299-1304 Journal article (peer-reviewed)abstract Four new naphthohydroquinones, named busseihydroquinones A–D (1–4), along with a known homoprenylated dihydronaphthoquinone (5), were isolated from the CH2Cl2/MeOH (1:1) extract of the roots of Pentas bussei. Although the genus Pentas is frequently used by traditional healers for the treatment of malaria, only marginal activities against the chloroquine-sensitive (D6) and the chloroquine-resistant (W2) strains of Plasmodium falciparum were observed for the crude root extract and the isolated constituents of this plant.
24.	Gumula, Ivan, et al. (author) Flemingins G–O, Cytotoxic and Antioxidant Constituents of the Leaves of Flemingia grahamiana 2014 In: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 77:9, s. 2060-2067 Journal article (peer-reviewed)abstract The known flemingins A–C (1–3) and nine new chalcones, named flemingins G–O (4–12), along with deoxyhomoflemingin (13) and emodin (14) were isolated from a leaf extract of Flemingia grahamiana. The isolated chalcones were found to have a geranyl substituent modified into a chromene ring possessing a residual chain, as shown by spectroscopic methods. The leaf extract showed an IC50 value of 5.9 μg/mL in a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. The chalcones flemingins A, B, C, G, and H were active in the DPPH radical scavenging assay (ED50 4.4–8.9 μM), while flemingins A and C showed cytotoxicity against MCF-7 human breast cancer cells (IC50 8.9 and 7.6 μM, respectively).
25.	Jansson, Kristina, 1969, et al. (author) A role for Myh1 in DNA repair after treatment with strand-breaking and crosslinking chemotherapeutic agents 2013 In: Environmental and Molecular Mutagenesis. - : Wiley. - 0893-6692 .- 1098-2280. ; 54:5, s. 327-337 Journal article (peer-reviewed)abstract The highly conserved DNA glycosylase MutY is implicated in repair of oxidative DNA damage, in particular in removing adenines misincorporated opposite 7,8-dihydro-8-oxoguanine (8-oxo-G). The MutY homologues (MutYH) physically associate with proteins implicated in replication, DNA repair, and checkpoint signaling, specifically with the DNA damage sensor complex 9-1-1 proteins. Here, we ask whether MutYH could have a broader function in sensing and repairing different types of DNA damage induced by conventional chemotherapeutics. Thus, we examined if deletion of the Schizosaccharomyces pombe MutY homologue, Myh1, alone or in combination with deletion of either component of the 9-1-1 sensor complex, influences survival after exposure to different classes of DNA damaging chemotherapeutics that do not act primarily by causing 8-oxoG lesions. We show that Myh1 contributes to survival on genotoxic stresses induced by the oxidizing, DNA double strand break-inducing, bleomycins, or the DNA crosslinking platinum compounds, particularly in a rad1 mutant background. Exposure of cells to cisplatin leads to a moderate overall accumulation of Myh1 protein. Interestingly, we found that DNA damage induced by phleomycin results in increased chromatin association of Myh1. Further, we demonstrate that Myh1 relocalizes to the nucleus after exposure to hydrogen peroxide or chemotherapeutics, most prominently seen after phleomycin treatment. These observations indicate a wider role of Myh1 in DNA repair and DNA damage-induced checkpoint activation than previously thought
26.	Poon, Jia-Fei, et al. (author) Azastilbenes : a cut-off to p38 MAPK inhibitors 2013 In: Organic and biomolecular chemistry. - : RSC Publishing. - 1477-0520 .- 1477-0539. ; 11:27 Journal article (peer-reviewed)
27.	Poon, Jia-Fei, et al. (author) Azastilbenes : a cut-off to p38 MAPK inhibitors 2013 In: Organic and biomolecular chemistry. - 1477-0520 .- 1477-0539. ; 11:27, s. 4526-4536 Journal article (peer-reviewed)abstract Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38[small alpha] assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.
28.	Poon, Jia-Fei, et al. (author) Azastilbenes: a cut-off to p38 MAPK inhibitors 2013 In: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 11:27, s. 4526-4536 Journal article (peer-reviewed)abstract Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38α assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.

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