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Issue 10, 2012
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New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity

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Abstract

A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF3, CO2Me) have been synthesized by a one-pot Suzuki–Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C–H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.

Graphical abstract: New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity

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Publication details

The article was received on 06 Oct 2011, accepted on 05 Dec 2011 and first published on 07 Dec 2011


Article type: Paper
DOI: 10.1039/C2OB06695E
Citation: Org. Biomol. Chem., 2012,10, 2101-2112
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    New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity

    S. Soto, E. Vaz, C. Dell'Aversana, R. Álvarez, L. Altucci and Á. R. de Lera, Org. Biomol. Chem., 2012, 10, 2101
    DOI: 10.1039/C2OB06695E

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