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Issue 27, 2014
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Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

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Abstract

An important determinant of the growth inhibitory activity of indolequinones against pancreatic cancer cells is substitution on the 2-position with 2-unsubstituted derivatives being markedly more potent. A series of indolequinones bearing a range of substituents on nitrogen and at the indolylcarbinyl position was prepared by copper(II)-mediated reaction of bromoquinones and enamines, followed by functional group interconversions. The compounds were then assayed for their ability to inhibit the growth of pancreatic cancer cells. The pKa of the leaving group at the 3-position was shown to influence growth inhibitory activity that is consistent with the proposed mechanism of action of reduction, loss of leaving group and formation of a reactive iminium species. Substitutions on the indole nitrogen were well tolerated with little influence on growth inhibitory activity while substitutions at the 5- and 6-positions larger than methoxy led to decreased activity. The studies presented define the range of substitutions of 2-unsubstituted indolequinones required for optimal growth inhibitory activity.

Graphical abstract: Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

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Publication details

The article was received on 03 Apr 2014, accepted on 13 May 2014 and first published on 13 May 2014


Article type: Paper
DOI: 10.1039/C4OB00711E
Citation: Org. Biomol. Chem., 2014,12, 4848-4861
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    Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells

    M. Inman, A. Visconti, C. Yan, D. Siegel, D. Ross and C. J. Moody, Org. Biomol. Chem., 2014, 12, 4848
    DOI: 10.1039/C4OB00711E

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