Top co-authors See all
Michael A. Strauss
572 shared publications
Donald G. York
472 shared publications
298 shared publications
252 shared publications
Phytopharmaceutical and Nutraceutical Research Laboratories (PNRL), Institute of Chemical Sciences, University of Peshawar
209 shared publications
Distribution of Articles published per year
(1898 - 2018)
(1898 - 2018)
Total number of journals
Publications See all
Article 0 Reads 0 Citations Multi-target mode of action of a Clerodane-type diterpenoid from Polyalthia longifolia targeting African trypanosomes Published: 15 March 2018
Scientific Reports, doi: 10.1038/s41598-018-22908-3
Article 3 Reads 0 Citations 3-Hydroxynaphthalene-2-carboxanilides and their antitrypanosomal activity Published: 06 February 2018
Monatshefte f�r Chemie, doi: 10.1007/s00706-017-2099-1
Series of ring-substituted 3-hydroxynaphthalene-2-carboxanilides were screened for their in vitro activity against wild-type S427 (bloodstream form) of Trypanosoma brucei brucei. 3-Hydroxy-N-(3-trifluoromethylphenyl)- and 3-hydroxy-N-(4-trifluoromethylphenyl)naphthalene-2-carboxamides showed the highest biological activity (MIC = 1.56 and 2.08 µmol/dm3, respectively). Antitrypanosomal activity was correlated with the experimentally determined lipophilicity and acid–base dissociation constants of the compounds as well as with the calculated electronic properties of individual anilide substituents expressed as Hammett’s σ parameters. The substitution in the meta- or para-position of anilide of derivatives with higher lipophilicity by an electron-withdrawing moiety is favourable for higher activity. The optimum thermodynamic pK aT value was found to be ca. 7.5. The structure–activity relationships of all compounds are discussed.
Article 0 Reads 0 Citations Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Bioma... Published: 24 July 2017
Journal of Medicinal Chemistry, doi: 10.1021/acs.jmedchem.7b00484
IKKβ plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The role of IKKα in the noncanonical NF-kB pathway, and indeed in the canonical pathway as a complex with IKKβ, is less well understood. One major reason for this is the absence of chemical tools designed as selective inhibitors for IKKα over IKKβ. Herein, we report for the first time a series of novel, potent, and selective inhibitors of IKKα. We demonstrate effective target engagement and selectivity with IKKα in U2OS cells through inhibition of IKKα-driven p100 phosphorylation in the noncanonical NF-kB pathway without affecting IKKβ-dependent IKappa-Bα loss in the canonical pathway. These compounds represent the first chemical tools that can be used to further characterize the role of IKKα in cellular signaling, to dissect this from IKKβ and to validate it in its own right as a target in inflammatory diseases.
Article 0 Reads 0 Citations The Chemical Characterization of Nigerian Propolis samples and Their Activity Against Trypanosoma brucei Published: 19 April 2017
Scientific Reports, doi: 10.1038/s41598-017-01038-2
Profiling of extracts from twelve propolis samples collected from eight regions in Nigeria was carried out using high performance liquid chromatography (LC) coupled with evaporative light scattering (ELSD), ultraviolet detection (UV) and mass spectrometry (MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). Principal component analysis (PCA) of the processed LC-MS data demonstrated the varying chemical composition of the samples. Most of the samples were active against Trypanosoma b. brucei with the highest activity being in the samples from Southern Nigeria. The more active samples were fractionated in order to isolate the component(s) responsible for their activity using medium pressure liquid chromatography (MPLC). Three xanthones, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, 1,3,7-trihydroxy-4,8-di-(3-methylbut-2-enyl)xanthone a previously undescribed xanthone and three triterpenes: ambonic acid, mangiferonic acid and a mixture of α-amyrin with mangiferonic acid (1:3) were isolated and characterised by NMR and LC-MS. These compounds all displayed strong inhibitory activity against T.b. brucei but none of them had higher activity than the crude extracts. Partial least squares (PLS) modelling of the anti-trypanosomal activity of the sample extracts using the LC-MS data indicated that high activity in the extracts, as judged from LCMS2 data, could be correlated to denticulatain isomers in the extracts.
Article 0 Reads 0 Citations A globally deployable strategy for co-development of adaptation preferences to sea-level rise: the public participation ... Published: 09 April 2017
Natural Hazards, doi: 10.1007/s11069-017-2855-x
Sea-level rise (SLR) poses a range of threats to natural and built environments in coastal zones around the world. Assessment of the risks due to exposure and sensitivity of coastal communities to coastal flooding is essential for informed decision-making. Strategies for public understanding and awareness of the tangible effects of climate change are fundamental in developing policy options. A multidisciplinary, multinational team of natural and social scientists from the USA, the UK, and Brazil developed the METROPOLE Project to evaluate how local governments may decide between adaptation options associated with SLR projections. METROPOLE developed a participatory approach in which public actors engage fully in defining the research problem and evaluating outcomes. Using a case study of the city of Santos, in Brazil, METROPOLE developed a method for evaluating risks jointly with the community, comparing ‘no-action’ to ‘adaptation’ scenarios. At the core of the analysis are estimates of economic costs of the impact of floods on urban real estate under SLR projections through 2050 and 2100. Results helped identify broad preferences and orientations in adaptation planning, which the community, including the Santos municipal government, co-developed in a joint effort with natural and social scientists.
Article 0 Reads 5 Citations AMPK Causes Cell Cycle Arrest in LKB1-deficient Cells via Activation of CAMKK2 Published: 02 May 2016
Molecular Cancer Research, doi: 10.1158/1541-7786.mcr-15-0479
The AMP-activated protein kinase (AMPK) is activated by phosphorylation at Thr172, either by the tumor suppressor kinase LKB1 or by an alternate pathway involving the Ca2+/calmodulin-dependent kinase, CAMKK2. Increases in AMP:ATP and ADP:ATP ratios, signifying energy deficit, promote allosteric activation and net Thr172 phosphorylation mediated by LKB1, so that the LKB1-AMPK pathway acts as an energy sensor. Many tumor cells carry loss-of-function mutations in the STK11 gene encoding LKB1, but LKB1 re-expression in these cells causes cell cycle arrest. Therefore, it was investigated as to whether arrest by LKB1 is caused by activation of AMPK or of one of the AMPKrelated kinases, which are also dependent on LKB1 but are not activated by CAMKK2. In three LKB1-null tumor cell lines, treatment with the Ca2+ ionophore A23187 caused a G1-arrest that correlated with AMPK activation and Thr172 phosphorylation. In G361 cells, expression of a truncated, CAMKK2 mutant also caused G1-arrest similar to that caused by expression of LKB1, while expression of a dominant negative AMPK mutant, or a double knockout of both AMPK-alpha subunits, also prevented the cell cycle arrest caused by A23187. These mechanistic findings confirm that AMPK activation triggers cell cycle arrest, and also suggest that the rapid proliferation of LKB1-null tumor cells is due to lack of the restraining influence of AMPK. However, cell cycle arrest can be restored by re-expressing LKB1 or a constitutively active CAMKK2, or by pharmacological agents that increase intracellular Ca2+ and thus activate endogenous CAMKK2. Implications: Evidence here reveals that the rapid growth and proliferation of cancer cells lacking the tumor suppressor LKB1 is due to reduced activity of AMPK, and suggests a therapeutic approach by which this block might be circumvented.