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12 results on '"Hollingsworth I"'

9. Effect of landuse on the composition of throughflow water immediately above clayey B horizons in the Warren Catchment, South Australia

Author

Ravi Naidu, Rob Fitzpatrick, I. Hollingsworth, Williamson, Williamson, D R, Fitzpatrick, R W, and Hollingsworth, I O

Subjects
Hydrology, Salinity, Throughflow, Irrigation, Lysimeter, Soil water, Dissolved organic carbon, Environmental science, Water quality, General Agricultural and Biological Sciences, Total dissolved solids
Abstract

The effect of landuse on composition of throughflow water immediately above the clayey B horizons in duplex soils (mostly natric and/or sodic) in the Mount Lofty Ranges, South Australia, was investigated using simple lysimeters. During July-November 1991, the pH of the first flow immediately after rainstorm under pines, native woodland, and pasture, respectively, was 5.7, 6.0, and 6.4. At each of the sites, average pH over 4 months during July-November was 5.8-5.9. Both the electrical conductivity (EC) and the amounts of total dissolved solids (TDS) were 2-3 times higher under pine than at other sites. The rate of change in EC with respect to TDS varied considerably among the sites, possibly due to the large differences in the concentration of dissolved organic compounds. Although the pH of water was >5.5, both aluminium and iron were recorded, especially under pine, where there were also high levels of dissolved organic compounds. High levels of suspended colloidal matter were recorded in the water flowing under pine, and these levels were related to dissolved organic carbon.

Published
1993

10. Correction to "Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models".

Author

Finlay MRV, Anderton M, Bailey A, Boyd S, Brookfield J, Cairnduff C, Charles M, Cheasty A, Critchlow SE, Culshaw J, Debreczeni J, Ekwuru T, Hollingsworth I, Jones N, Leroux F, Littleson M, McCarron H, McKelvie J, Mooney L, Nissink JWM, Patel J, Perkins D, Powell S, Quesada MJ, Raubo P, Sabin V, Smith J, Smith PD, Stark A, Ting A, Wang P, Wilson Z, Winter-Holt JJ, Wood JM, Wrigley GL, Yu G, and Zhang P

Published
2023
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11. Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models.

Author

Finlay MRV, Anderton M, Bailey A, Boyd S, Brookfield J, Cairnduff C, Charles M, Cheasty A, Critchlow SE, Culshaw J, Ekwuru T, Hollingsworth I, Jones N, Leroux F, Littleson M, McCarron H, McKelvie J, Mooney L, Nissink JWM, Perkins D, Powell S, Quesada MJ, Raubo P, Sabin V, Smith J, Smith PD, Stark A, Ting A, Wang P, Wilson Z, Winter-Holt JJ, Wood JM, Wrigley GL, Yu G, and Zhang P

Subjects
Animals, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Biological Availability, Cell Line, Tumor, Drug Discovery, Glutaminase metabolism, Humans, Male, Mice, SCID, Molecular Docking Simulation, Neoplasms metabolism, Neoplasms pathology, Pyridazines chemistry, Pyridazines pharmacokinetics, Pyridazines therapeutic use, Thiadiazoles chemistry, Thiadiazoles pharmacokinetics, Thiadiazoles therapeutic use, Antineoplastic Agents pharmacology, Glutaminase antagonists & inhibitors, Neoplasms drug therapy, Pyridazines pharmacology, Thiadiazoles pharmacology
Abstract

Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers by blocking the tumor cell's ability to produce glutamine-derived nutrients. Starting from the known GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide, we describe the medicinal chemistry evolution of a series from lipophilic inhibitors with suboptimal physicochemical and pharmacokinetic properties to cell potent examples with reduced molecular weight and lipophilicity, leading to compounds with greatly improved oral exposure that demonstrate in vivo target engagement accompanied by activity in relevant disease models.

Published
2019
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12. Synthesis of functionalized cyanopyrazoles via magnesium bases.

Author

Dishington A, Feron JL, Gill K, Graham MA, Hollingsworth I, Pink JH, Roberts A, Simpson I, and Tatton M

Subjects
Combinatorial Chemistry Techniques, Molecular Structure, Nitriles chemistry, Organometallic Compounds chemistry, Pyrazoles chemistry, Stereoisomerism, Hydrocarbons, Halogenated chemistry, Magnesium chemistry, Nitriles chemical synthesis, Pyrazoles chemical synthesis
Abstract

4-Alkyl- and 4-H-pyrazoles were sequentially metalated using TMPMgCl·LiCl, and their reaction with electrophiles afforded 3-aryl-4-alkyl-5-cyanopyrazoles.

Published
2014
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