Aroyl-pyrrolyl hydroxyamides: influence of pyrrole C4-phenylacetyl substitution on histone deacetylase inhibition.

Translated title of the contribution: [Autom. eng. transl.] Aroyl-pyrrolyl hydroxyamides: influence of pyrrole C4-phenylacetyl substitution on histone deacetylase inhibition.

Roberto Scatena, Patrizia Bottoni

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The novel aroyl-pyrrolyl hydroxyamides 4 a-a' are analogues of the lead compound 3-(1-methyl-4-phenylacetyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (2) and are active as HDAC inhibitors. The benzene ring of 2 was substituted with a wide range of electron-donating and electron-withdrawing groups, and the effect was evaluated on three HDACs from maize, namely HD2, HD1-B (a class I HDAC), and HD1-A (a class II HDAC). Inhibition studies show that the benzene 3' and, to a lesser extent, 4' positions of 2 were the most suitable for the introduction of substituents, with the 3'-chloro (in 4 b) and the 3'-methyl (in 4 k) derivatives being the most potent compounds, reaching the same activity as SAHA. Inhibition data for 4 b,k against mouse HDAC1 were consistent with those observed in the maize enzyme. The substituent insertion on the benzene ring of 2 (compounds 4 a-a') abated the slight (3-fold) selectivity for class II HDACs displayed by 2. Compound 4 b showed interesting, dose-dependent antiproliferative and cytodifferentiation properties against human acute promyelocytic leukemia HL-60 cells.
Translated title of the contribution[Autom. eng. transl.] Aroyl-pyrrolyl hydroxyamides: influence of pyrrole C4-phenylacetyl substitution on histone deacetylase inhibition.
Original languageItalian
Pages (from-to)225-237
Number of pages13
JournalChemMedChem
Publication statusPublished - 2006

Keywords

  • HDAC
  • cancer
  • differentiation

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