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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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Supplementary files

Article information


Submitted
06 Oct 2011
Accepted
05 Dec 2011
First published
07 Dec 2011

Org. Biomol. Chem., 2012,10, 2101-2112
Article type
Paper

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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