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Your search keyword '"Mirella A. Keane"' showing total 2 results
Start Over Author "Mirella A. Keane" Topic organic chemistry
2 results on '"Mirella A. Keane"'

1. Anhydride modified cantharidin analogues. Is ring opening important in the inhibition of protein phosphatase 2A?

Author

Jennette A. Sakoff, Lisa-Maree Mudgee, Adam McCluskey, Alistair T. R. Sim, Ronald J. Quinn, and Mirella A. Keane

Subjects
Pharmacology, Cantharidin, Magnetic Resonance Spectroscopy, Molecular Structure, Stereochemistry, Organic Chemistry, General Medicine, Protein phosphatase 2, Ring (chemistry), Anhydrides, chemistry.chemical_compound, chemistry, Drug Discovery, Phosphoprotein Phosphatases, Moiety, Protein Phosphatase 2, Enzyme Inhibitors
Abstract

A series of anhydride modified cantharidin analogues have been synthesised and screened for their ability to inhibit protein phosphatase 2A. Surprisingly only analogues capable of undergoing a facile ring opening of the anhydride moiety displayed any significant inhibition. Subsequent NMR experiments indicated that 7-oxobicyclo[2.2.1]heptane-2,3-dicarboxylic acid was the major (sole) species under assay conditions. The ability of these modified anhydro-cantharidin analogues to inhibit protein phosphatase 2A varies from 4 (16) to 100% (8) at 100 μM test concentration.

Published
2000
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2. The first two cantharidin analogues displaying PP1 selectivity

Author

Mirella A. Keane, Jennette A. Sakoff, Michael C. Bowyer, David J. Young, Adam McCluskey, Cecilia C. Walkom, and Alistair T. R. Sim

Subjects
Cantharidin, Bicyclic molecule, Stereochemistry, Organic Chemistry, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Chemical synthesis, Substrate Specificity, chemistry.chemical_compound, Structure-Activity Relationship, chemistry, Furan, Drug Discovery, Thiophene, Phosphoprotein Phosphatases, Molecular Medicine, Indicators and Reagents, Enzyme Inhibitors, Selectivity, Imide, Molecular Biology, Maleimide
Abstract

High pressure Diels-Alder reactions of furan and dimethylmaleate, and thiophene and maleimide resulted in two cantharidin analogues, 3 and 6 possessing PP1 selectivity (>40- and >30-fold selectivity) over PP2A. Both compounds exhibited moderate PP1 activity, 3 IC 50 50 μM and 6 IC 50 12.5 μM. Interestingly, the corresponding mono-ester derivatives of 3 showed no such selectivity.

Published
2002

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