New synthetic approach to paullones and characterization of their SIRT1 inhibitory activityElectronic supplementary information (ESI) available: Experimental procedures, analytical and spectral characterization data for compounds not included in the text. See DOI: 10.1039/c2ob06695e

• Main Authors: Soto, Sara, Vaz, Esther, Dell'Aversana, Carmela, lvarez, Rosana, Altucci, Lucia, de Lera, ngel R
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c2ob06695e

A series of 7,12-dihydroindolo[3,2- d ][1]benzazepine-6(5 H )-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF 3 , CO 2 Me) have been synthesized by a one-pot SuzukiMiyaura 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 CH 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. New paullones, synthesized by a one-pot SuzukiMiyaura intramolecular amidation, strongly inhibited hSIRT-1 and induced granulocyte differentiation of the U937 leukemia cell line.