Antiproliferative activities of a library of hybrids between indanones and HDAC inhibitor SAHA and MS-275 analogues

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6142-6. doi: 10.1016/j.bmcl.2007.09.041. Epub 2007 Sep 14.

Abstract

New compounds derived from inhibitors of histone deacetylases (HDACs) have been synthesized and their antiproliferative activities towards non small lung cancer cell line H661 evaluated. Their design is based on hybrids between indanones to limit conformational mobility and other known HDAC inhibitors (SAHA, MS-275). The synthesis of these new derivatives was achieved by alkylation of appropriate indanones to introduce the side chain bearing a terminal ester group, the latter being a precursor of hydroxamic acid and aminobenzamide derivatives. These new analogues were found to be moderately active to inhibit H661 cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Benzamides / chemistry
  • Benzamides / metabolism
  • Benzamides / pharmacology*
  • Binding Sites / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors*
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / metabolism
  • Hydroxamic Acids / pharmacology*
  • Indans / chemical synthesis
  • Indans / metabolism
  • Indans / pharmacology*
  • Molecular Structure
  • Pyridines / chemistry
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Vorinostat

Substances

  • Antineoplastic Agents
  • Benzamides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Indans
  • Pyridines
  • entinostat
  • Vorinostat