New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity
作者： Sara Soto , Esther Vaz , Carmela Dell'Aversana , Rosana Álvarez , Lucia Altucci
DOI: 10.1039/C2OB06695E
关键词:
摘要: 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 an o-aminoarylboronic acid methyl 2-iodoindoleacetate followed 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 strong inhibitory profile for series, in particular analogue methoxycarbonyl group bromine C9. These compounds are, general, inducers granulocyte differentiation U937 acute leukemia cell line cause marked increase pre-G1 cycle.
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