Premium
Azetidinones as Zinc‐Binding Groups to Design Selective HDAC8 Inhibitors
Author(s) -
Galletti Paola,
Quintavalla Arianna,
Ventrici Caterina,
Giannini Giuseppe,
Cabri Walter,
Penco Sergio,
Gallo Grazia,
Vincenti Silvia,
Giacomini Daria
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900309
Subject(s) - hdac8 , substituent , selectivity , chemistry , gene isoform , stereochemistry , nitrogen atom , in vitro , combinatorial chemistry , ring (chemistry) , biochemistry , epigenetics , organic chemistry , gene , catalysis , histone methyltransferase
2‐Azetidinones, commonly known as β‐lactams, are well‐known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel β‐lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform‐selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone‐ring nitrogen atom substituent. The presence of an N ‐thiomethyl group is a prerequisite for the activity of these compounds in the micromolar range towards HDAC8.