945401-05-8Relevant academic research and scientific papers
Synthesis and anticancer activity of novel bisindolylhydroxymaleimide derivatives with potent GSK-3 kinase inhibition
Winfield, Hannah J.,Cahill, Michael M.,O'Shea, Kevin D.,Pierce, Larry T.,Robert, Thomas,Ruchaud, Sandrine,Bach, Stéphane,Marchand, Pascal,McCarthy, Florence O.
, p. 4209 - 4224 (2018/07/21)
Synthesis and biological evaluation of a series of novel indole derivatives as anticancer agents is described. A bisindolylmaleimide template has been derived as a versatile pharmacophore with which to pursue chemical diversification. Starting from maleimide, the introduction of an oxygen to the headgroup (hydroxymaleimide) was initially investigated and the bioactivity assessed by screening of kinase inhibitory activity, identifying substituent derived selectivity. Extension of the hydroxymaleimide template to incorporate substitution of the indole nitrogens was next completed and assessed again by kinase inhibition identifying unique selectivity patterns with respect to GSK-3 and CDK kinases. Subsequently, the anticancer activity of bisindolylmaleimides were assessed using the NCI-60 cell screen, disclosing the discovery of growth inhibitory profiles towards a number of cell lines, such as SNB-75 CNS cancer, A498 and UO-31 renal, MDA MB435 melanoma and a panel of leukemia cell lines. The potential for selective kinase inhibition by modulation of this template is evident and will inform future selective clinical candidates.
Synthesis of a novel N-nitroalkyl bisindolylmaleimide
Roy, Sudipta,Gribble, Gordon W.
, p. 1879 - 1886 (2008/02/03)
We describe the synthesis of the novel N-nitropropyl bisindolylmaleimide 6. Copyright Taylor & Francis Group, LLC.
Inhibitors of Protein Kinase C. 1. 2,3-Bisarylmaleimides
Davis, Peter D.,Hill, Christopher H.,Lawton, Geoffrey,Nixon, John S.,Wilkinson, Sandra E.,et al.
, p. 177 - 184 (2007/10/02)
The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described.These 2,3-bisarylmaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a.Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11 μM).In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67 μM).Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).
