Send to

Choose Destination
See comment in PubMed Commons below
Eur J Med Chem. 2009 May;44(5):1900-12. doi: 10.1016/j.ejmech.2008.11.005. Epub 2008 Nov 19.

Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors.

Author information

  • 1Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy.


A series of hydroxamic acid-based histone deacetylase (HDAC) inhibitors were designed on the basis of a model of the HDAC2 binding site and synthesized. They are characterized by a cinnamic spacer, capped with a substituted phenyl group. Modifications of the spacer are also reported. In an in vitro assay with the isoenzyme HDAC2, a good correlation of the activity with the docking energy was found. In human ovarian carcinoma IGROV-1 cells, selected compounds produced significant acetylation of p53 and alpha-tubulin. Most compounds showed an antiproliferative activity comparable to that of SAHA. At equitoxic concentrations, the tested compounds were more effective than SAHA in inducing apoptotic cell death. Compounds selected for in vivo evaluation exhibited a significant antitumor activity on three tumor models at well tolerated doses, thus suggesting a good therapeutic index.

[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

Chemical Information


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk